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Sample records for chromosomal kinase jil-1

  1. The Chriz–Z4 complex recruits JIL-1 to polytene chromosomes, a requirement for interband-specific phosphorylation of H3S10

    Indian Academy of Sciences (India)

    Miao Gan; Selina Moebus; Harald Eggert; Harald Saumweber

    2011-08-01

    The conserved band-interband pattern is thought to reflect the looped-domain organization of insect polytene chromosomes. Previously, we have shown that the chromodomain protein Chriz and the zinc-finger protein Z4 are essentially required for the maintenance of polytene chromosome structure. Here we show that both proteins form a complex that recruits the JIL-1 kinase to polytene chromosomes, enabling local H3S10 phosphorylation of interband nucleosomal histones. Interband targeting domains were identified at the N-terminal regions of Chriz and Z4, and our data suggest partial cooperation of the complex with the BEAF boundary element protein in polytene and diploid cells. Reducing the core component Chriz by RNAi results in destabilization of the complex and a strong reduction of interband-specific histone H3S10 phosphorylation.

  2. X-Ray Crystal Structure of Bone Marrow Kinase in the X Chromosome: A Tec Family Kinase

    Energy Technology Data Exchange (ETDEWEB)

    Muckelbauer, Jodi; Sack, John S.; Ahmed, Nazia; Burke, James; Chang, ChiehYing Y.; Gao, Mian; Tino, Joseph; Xie, Dianlin; Tebben, Andrew J. (BMS)

    2012-06-27

    Bone marrow kinase in the X chromosome, a member of the Tec family of tyrosine kinases, plays a role in both monocyte/macrophage trafficking as well as cytokine secretion. Although the structures of Tec family kinases Bruton's tyrosine kinase and IL-2-inducible T-cell kinase are known, the crystal structures of other Tec family kinases have remained elusive. We report the X-ray crystal structures of bone marrow kinase in the X chromosome in complex with dasatinib at 2.4 {angstrom} resolution and PP2 at 1.9 {angstrom} resolution. The bone marrow kinase in the X chromosome structures reveal a typical kinase protein fold; with well-ordered protein conformation that includes an open/extended activation loop and a stabilized DFG-motif rendering the kinase in an inactive conformation. Dasatinib and PP2 bind to bone marrow kinase in the X chromosome in the ATP binding pocket and display similar binding modes to that observed in other Tec and Src protein kinases. The bone marrow kinase in the X chromosome structures identify conformational elements of the DFG-motif that could potentially be utilized to design potent and/or selective bone marrow kinase in the X chromosome inhibitors.

  3. A Causal Gene for Seed Dormancy on Wheat Chromosome 4A Encodes a MAP Kinase Kinase.

    Science.gov (United States)

    Torada, Atsushi; Koike, Michiya; Ogawa, Taiichi; Takenouchi, Yu; Tadamura, Kazuki; Wu, Jianzhong; Matsumoto, Takashi; Kawaura, Kanako; Ogihara, Yasunari

    2016-03-21

    Seed germination under the appropriate environmental conditions is important both for plant species survival and for successful agriculture. Seed dormancy, which controls germination time, is one of the adaptation mechanisms and domestication traits [1]. Seed dormancy is generally defined as the absence of germination of a viable seed under conditions that are favorable for germination [2]. The seed dormancy of cultivated plants has generally been reduced during domestication [3]. Bread wheat (Triticum aestivum L.) is one of the most widely grown crops in the world. Weak dormancy may be an advantage for the productivity due to uniform emergence and a disadvantage for the risks of pre-harvest sprouting (PHS), which decreases grain quality and yield [4]. A number of quantitative trait loci (QTLs) controlling natural variation of seed dormancy have been identified on various chromosomes [5]. A major QTL for seed dormancy has been consistently detected on chromosome 4A [6-13]. The QTL was designated as a major gene, Phs1, which could be precisely mapped within a 2.6 cM region [14]. Here, we identified a mitogen-activated protein kinase kinase 3 (MKK3) gene (designated TaMKK3-A) by a map-based approach as a candidate gene for the seed dormancy locus Phs1 on chromosome 4A in bread wheat. Complementation analysis showed that transformation of a dormant wheat cultivar with the TaMKK3-A allele from a nondormant cultivar clearly reduced seed dormancy. Cultivars differing in dormancy had a single nonsynonymous amino acid substitution in the kinase domain of the predicted MKK3 protein sequence, which may be associated with the length of seed dormancy. PMID:26948878

  4. The Aurora B kinase in chromosome biorientation and spindle checkpoint signalling

    Directory of Open Access Journals (Sweden)

    Veronica eKrenn

    2015-10-01

    Full Text Available Aurora B, a member of the Aurora family of serine/threonine protein kinases, is a key player in chromosome segregation. As part of a macromolecular complex known as the chromosome passenger complex, Aurora B concentrates early during mitosis in the proximity of centromeres and kinetochores, the sites of attachment of chromosomes to spindle microtubules. There, it contributes to a number of processes that impart fidelity to cell division, including kinetochore stabilization, kinetochore-microtubule attachment, and the regulation of a surveillance mechanism named the spindle assembly checkpoint. In the regulation of these processes, Aurora B is the fulcrum of a remarkably complex network of interactions that feed back on its localization and activation state. In this review we discuss the multiple roles of Aurora B during mitosis, focusing in particular on its role at centromeres and kinetochores. Many details of the network of interactions at these locations remain poorly understood, and we focus here on several crucial outstanding questions.

  5. POLO-LIKE KINASE I CONTROLS NUCLEAR ENVELOPE BREAK DOWN AND CHROMOSOME DYNAMICS IN MEIOSIS I

    Czech Academy of Sciences Publication Activity Database

    Šolc, Petr; Kitajima, T.; Baran, V.; Brzáková, Adéla; Mayer, Alexandra; Samalová, Pavlína; Motlík, Jan; Ellenberg, J.

    Montpellier : EMBO, 2011. s. 203-203. [15th European Cell Cycle Conference and EMBO Workshop. 02.09.2011-05.09.2011, Montpellier] R&D Projects: GA ČR(CZ) GC301/09/J036; GA MŠk ME08030; GA ČR(CZ) GPP301/11/P081 Institutional research plan: CEZ:AV0Z50450515 Keywords : polo-like kinase * chromosome * meiosis I Subject RIV: EB - Genetics ; Molecular Biology http://events.embo.org/11-cell-cycle/

  6. Sli15 Associates with the Ipl1 Protein Kinase to Promote Proper Chromosome Segregation in Saccharomyces cerevisiae

    OpenAIRE

    Kim, Jae-Hyun; Kang, Jung-seog; Chan, Clarence S.M.

    1999-01-01

    The conserved Ipl1 protein kinase is essential for proper chromosome segregation and thus cell viability in the budding yeast Saccharomyces cerevisiae. Its human homologue has been implicated in the tumorigenesis of diverse forms of cancer. We show here that sister chromatids that have separated from each other are not properly segregated to opposite poles of ipl1-2 cells. Failures in chromosome segregation are often associated with abnormal distribution of the spindle pole–associated Nuf2-GF...

  7. Cloning, tissue expression pattern, and chromosome localization of human protein kinase Bγ gene

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Protein kinase B (PKB) is a member of the second messenger-regulated subfamily of protein kinases, and plays a key role in cell-cycle regulation, glucose uptake and promotion of cell differentiation. Evidence shows that PKB undergoes activation in some human tumors and is involved in Ras pathway, which implies that PKB can trigger a pathway to induce oncogenic transformation. A nucleotide sequence of mouse Pkb? was used as a probe to screen homolog in a human liver cDNA library. A fragment of 1998 bp containing a 1440 bp ORF encoding 479 amino acid residues was obtained. Then the 3'-terminal of this fragment was extended to 2788 bp by 'electronic walking' screening, and the extended fragment was confirmed by PCR amplification. The protein deduced by the gene had a high identity of 83% and 78% to the human PKBγ and γ, respectively, and was designated as human PKB?. Northern hybridization detected two equally expressed transcripts of 8.5 and 6.5 kb in length in all 16 human tissues tested, with the highest expression level in brain, and lower levels with variation in the other tissues. By RH mapping, the PKBγ was placed on chromosome 1q43, between markers D1S304 and D1S2693. It is a valuable clue for cloning the candidate genes related to prostate cancer; Arrhythmogenic Right Ventricular Dysplasia (ARVD); Chediak-Higashi, NK cell Deficiency (CHS); and Hypoparathyrodism with Short Stature, Mental Retardation and Seizures which have already been mapped in this chromosomal region.

  8. Rapid molecular cytogenetic analysis of X-chromosomal microdeletions: Fluorescence in situ hybridization (FISH) for complex glycerol kinase deficiency

    Energy Technology Data Exchange (ETDEWEB)

    Worley, K.C.; Lindsay, E.A.; McCabe, E.R.B. [Baylor College of Medicine, Houston, TX (United States)] [and others

    1995-07-17

    Diagnosis of X-chromosomal microdeletions has relied upon the traditional methods of Southern blotting and DNA amplification, with carrier identification requiring time-consuming and unreliable dosage calculations. In this report, we describe rapid molecular cytogenetic identification of deleted DNA in affected males with the Xp21 contiguous gene syndrome (complex glycerol kinase deficiency, CGKD) and female carriers for this disorder. CGKD deletions involve the genes for glycerol kinase, Duchenne muscular dystrophy, and/or adrenal hypoplasia congenita. We report an improved method for diagnosis of deletions in individuals with CGKD and for identification of female carriers within their families using fluorescence in situ hybridization (FISH) with a cosmid marker (cosmid 35) within the glycerol kinase gene. When used in combination with an Xq control probe, affected males demonstrate a single signal from the control probe, while female carriers demonstrate a normal chromosome with two signals, as well as a deleted chromosome with a single signal from the control probe. FISH analysis for CGKD provides the advantages of speed and accuracy for evaluation of submicroscopic X-chromosome deletions, particularly in identification of female carriers. In addition to improving carrier evaluation, FISH will make prenatal diagnosis of CGKD more readily available. 17 refs., 2 figs.

  9. Type 1 protein phosphatase acts in opposition to IpL1 protein kinase in regulating yeast chromosome segregation.

    OpenAIRE

    Francisco, L; Wang, W.; Chan, C S

    1994-01-01

    The IPL1 gene is required for high-fidelity chromosome segregation in the budding yeast Saccharomyces cerevisiae. Conditional ipl1ts mutants missegregate chromosomes severely at 37 degrees C. Here, we report that IPL1 encodes an essential putative protein kinase whose function is required during the later part of each cell cycle. At 26 degrees C, the permissive growth temperature, ipl1 mutant cells are defective in the recovery from a transient G2/M-phase arrest caused by the antimicrotubule ...

  10. Kinase Expression and Chromosomal Rearrangements in Papillary Thyroid Cancer Tissues: Investigations at the Molecular and Microscopic Levels

    International Nuclear Information System (INIS)

    Structural chromosome aberrations are known hallmarks of many solid tumors. In the papillary form of thyroid cancer (PTC), for example, activation of the receptor tyrosine kinase (RTK) genes, ret or the neurotrophic tyrosine kinase receptor type I (NTRK1) by intra- or interchromosomal rearrangements have been suggested as a cause of the disease. The 1986 accident at the nuclear power plant in Chernobyl, USSR, led to the uncontrolled release of high levels of radioisotopes. Ten years later, the incidence of childhood papillary thyroid cancer (chPTC) near Chernobyl had risen by two orders of magnitude. Tumors removed from some of these patients showed aberrant expression of the ret RTK gene due to a ret/PTC1 or ret/PTC3 rearrangement involving chromosome 10. However, many cultured chPTC cells show a normal G-banded karyotype and no ret rearrangement. We hypothesize that the 'ret-negative' tumors inappropriately express a different oncogene or have lost function of a tumor suppressor as a result of chromosomal rearrangements, and decided to apply molecular and cytogenetic methods to search for potentially oncogenic chromosomal rearrangements in Chernobyl chPTC cases. Knowledge of the kind of genetic alterations may facilitate the early detection and staging of chPTC as well as provide guidance for therapeutic intervention.

  11. Kinase Expression and Chromosomal Rearrangements in Papillary Thyroid Cancer Tissues: Investigations at the Molecular and Microscopic Levels

    Energy Technology Data Exchange (ETDEWEB)

    Weier, Heinz-Ulrich; Kwan, Johnson; Lu, Chun-Mei; Ito, Yuko; Wang, Mei; Baumgartner, Adolf; Hayward, Simon W.; Weier, Jingly F.; Zitzelsberger, Horst F.

    2009-07-07

    Structural chromosome aberrations are known hallmarks of many solid tumors. In the papillary form of thyroid cancer (PTC), for example, activation of the receptor tyrosine kinase (RTK) genes, ret or the neurotrophic tyrosine kinase receptor type I (NTRK1) by intra- or interchromosomal rearrangements have been suggested as a cause of the disease. The 1986 accident at the nuclear power plant in Chernobyl, USSR, led to the uncontrolled release of high levels of radioisotopes. Ten years later, the incidence of childhood papillary thyroid cancer (chPTC) near Chernobyl had risen by two orders of magnitude. Tumors removed from some of these patients showed aberrant expression of the ret RTK gene due to a ret/PTC1 or ret/PTC3 rearrangement involving chromosome 10. However, many cultured chPTC cells show a normal G-banded karyotype and no ret rearrangement. We hypothesize that the 'ret-negative' tumors inappropriately express a different oncogene or have lost function of a tumor suppressor as a result of chromosomal rearrangements, and decided to apply molecular and cytogenetic methods to search for potentially oncogenic chromosomal rearrangements in Chernobyl chPTC cases. Knowledge of the kind of genetic alterations may facilitate the early detection and staging of chPTC as well as provide guidance for therapeutic intervention.

  12. The human gene for neurotrophic tyrosine kinase receptor type 2 (NTRK2) is located on chromosome 9 but is not the familial dysautonomia gene

    Energy Technology Data Exchange (ETDEWEB)

    Slaugenhaupt, S.A. [Massachusetts General Hospital, Boston, MA (United States)]|[Harvard Medical School, Boston, MA (United States); Liebert, C.B.; Lucente, D.E. [Massachusetts General Hospital, Boston, MA (United States)] [and others

    1995-02-10

    The neurotrophic tyrosine kinase receptor type 2 (NTRK2) gene is a member of the trk family of tyrosine protein kinases, which encode receptors for the nerve growth factor-related proteins known as neurotrophins. The neurotrophins and their receptors have long been considered candidate genes for familial dysautonomia (FD), a hereditary sensory neuropathy resulting from the congenital loss of both sensory and autonomic neurons. The DYS gene has recently been mapped to human chromosome 9q31-q33, and therefore we set out to determine the chromosomal localization of the candidate gene NTRK2. A mouse trkB probe was hybridized to both somatic cell hybrids containing human chromosome 9 and a human chromosome 9 flow-sorted cosmid library. The human homologue of trkB, NTRK2, was assigned to chromosome 9. To localize the NTRK2 gene further, a dinucleotide repeat polymorphism was identified within a cosmid that contains NTRK2 exon sequences. This marker was genotyped in the CEPH reference pedigrees and places the NTRK2 gene near D9S1 on the proximal long arm of human chromosome 9. The NTRK2 gene is located approximately 22 cm proximal to DYS and shows several recombinants in disease families. Therefore, the NTRK2 gene can now be excluded as a candidate gene for familial dysautonomia. 18 refs., 1 fig.

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

    Directory of Open Access Journals (Sweden)

    Yu-Hsin Chang

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

  14. LPIN1 deficiency with severe recurrent rhabdomyolysis and persistent elevation of creatine kinase levels due to chromosome 2 maternal isodisomy

    Directory of Open Access Journals (Sweden)

    I.A. Meijer

    2015-12-01

    Full Text Available Fatty acid oxidation disorders and lipin-1 deficiency are the commonest genetic causes of rhabdomyolysis in children. We describe a lipin-1-deficient boy with recurrent, severe rhabdomyolytic episodes from the age of 4 years. Analysis of the LPIN1 gene that encodes lipin-1 revealed a novel homozygous frameshift mutation in exon 9, c.1381delC (p.Leu461SerfsX47, and complete uniparental isodisomy of maternal chromosome 2. This mutation is predicted to cause complete lipin-1 deficiency. The patient had six rhabdomyolytic crises, with creatine kinase (CK levels up to 300,000 U/L (normal, 30 to 200. Plasma CK remained elevated between crises. A treatment protocol was instituted, with early aggressive monitoring, hydration, electrolyte replacement and high caloric, high carbohydrate intake. The patient received dexamethasone during two crises, which was well-tolerated and in these episodes, peak CK values were lower than in preceding episodes. Studies of anti-inflammatory therapy may be indicated in lipin-1 deficiency.

  15. Influence of different chromosomal abnormalities in Ph-positive bone marrow cells on the chronic myeloid leukemia course during tyrosine kinase inhibitors therapy

    Directory of Open Access Journals (Sweden)

    O. Yu. Vinogradova

    2012-01-01

    Full Text Available The additional molecular and chromosomal abnormalities (ACA in Phositive cells usually considered as a genetic marker of chronic myeloid leukemia (CML progression. 457 patients in different CML phases received tyrosine kinase inhibitors (1st and 2nd generation were studied. During therapy 50 cases with additional chromosomal abnormalities in Ph+ clone (22 of them in chronic CML phase were revealed (median follow-up from CML diagnosis – 117 months, median imatinib therapy – 62 months. 86 % of patients in chronic phase with Ph+- cell abnormalities were cytogenetic resistance, and their 5-years overall survival was 80 % which was significantly lower than in patients without ACA (p < 0.005. The treatment results depend on chromosomal abnormalities detected. In patients with additional chromosome 8 imatinib therapy is effective, although complete cytogenetic response (CCR is achieved only in the later therapy stages. In patients with additional translocations CCR also achieved with imatinib or 2nd generation TKI. Only a third of patients with additional Ph-chromosome or BCR/ABL amplification achieved complete suppression of Ph+ clone using 2nd generation TKI. The presence of additional chromosome 7 abnormalities and complex karyotype disorders involving isochromosome i(17(q10 are poor prognostic factors of TKI treatment failures.

  16. Influence of different chromosomal abnormalities in Ph-positive bone marrow cells on the chronic myeloid leukemia course during tyrosine kinase inhibitors therapy

    Directory of Open Access Journals (Sweden)

    O. Yu. Vinogradova

    2014-07-01

    Full Text Available The additional molecular and chromosomal abnormalities (ACA in Phositive cells usually considered as a genetic marker of chronic myeloid leukemia (CML progression. 457 patients in different CML phases received tyrosine kinase inhibitors (1st and 2nd generation were studied. During therapy 50 cases with additional chromosomal abnormalities in Ph+ clone (22 of them in chronic CML phase were revealed (median follow-up from CML diagnosis – 117 months, median imatinib therapy – 62 months. 86 % of patients in chronic phase with Ph+- cell abnormalities were cytogenetic resistance, and their 5-years overall survival was 80 % which was significantly lower than in patients without ACA (p < 0.005. The treatment results depend on chromosomal abnormalities detected. In patients with additional chromosome 8 imatinib therapy is effective, although complete cytogenetic response (CCR is achieved only in the later therapy stages. In patients with additional translocations CCR also achieved with imatinib or 2nd generation TKI. Only a third of patients with additional Ph-chromosome or BCR/ABL amplification achieved complete suppression of Ph+ clone using 2nd generation TKI. The presence of additional chromosome 7 abnormalities and complex karyotype disorders involving isochromosome i(17(q10 are poor prognostic factors of TKI treatment failures.

  17. Molecular cloning, cDNA sequence, and chromosomal localization of the human phosphatidylinositol 3-kinase p110{alpha} (PIK3CA) gene

    Energy Technology Data Exchange (ETDEWEB)

    Volinia, S.; Hiles, I.; Waterfield, M.D. [Ludwig Institute for Cancer Research, London (United Kingdom)] [and others

    1994-12-01

    Phosphatidylinositol (PI) 3-kinase is a heterodimeric enzyme comprising a 110-kDa catalytic subunit and an 85-kDa regulatory subunit that binds to tyrosine phosphopeptide sites linked directly or indirectly to receptors serving diverse signal functions. Knowledge of the structure and function of PI 3-kinase was greatly advanced by the purification, cDNA cloning, and subsequent expression of the bovine enzyme. Here the cloning of the cDNA for the human p110{alpha}subunit of PI 3-kinase (PIK3CA), encoding a protein 99% identical to the bovine p110, and of its gene in YAC is described. The chromosomal localization of the gene for PIK3CA is shown to be at 3q21-qter as determined using somatic cell hybrids. In situ hybridization performed using Alu-PCR from the YAC DNA located the gene in 3q26.3. 30 refs., 3 figs., 1 tab.

  18. Evolution and tinkering: what do a protein kinase, a transcriptional regulator and chromosome segregation/cell division proteins have in common?

    Science.gov (United States)

    Derouiche, Abderahmane; Shi, Lei; Kalantari, Aida; Mijakovic, Ivan

    2016-02-01

    In this study, we focus on functional interactions among multi-domain proteins which share a common evolutionary origin. The examples we develop are four Bacillus subtilis proteins, which all possess an ATP-binding Walker motif: the bacterial tyrosine kinase (BY-kinase) PtkA, the chromosome segregation protein Soj (ParA), the cell division protein MinD and a transcription regulator SalA. These proteins have arisen via duplication of the ancestral ATP-binding domain, which has undergone fusions with other functional domains in the process of divergent evolution. We point out that these four proteins, despite having very different physiological roles, engage in an unusually high number of binary functional interactions. Namely, MinD attracts Soj and PtkA to the cell pole, and in addition, activates the kinase function of PtkA. SalA also activates the kinase function of PtkA, and it gets phosphorylated by PtkA as well. The consequence of this phosphorylation is the activation of SalA as a transcriptional repressor. We hypothesize that these functional interactions remain preserved during divergent evolution and represent a constraint on the process of evolutionary "tinkering", brought about by fusions of different functional domains. PMID:26286503

  19. Casein kinases

    DEFF Research Database (Denmark)

    Issinger, O G

    1993-01-01

    subunits are highly conserved during evolution. The relationship between CK-2 alpha from humans and plants is still 73%. Similar relationships are reported for the beta-subunit. Chromosomal assignment of CK-2 alpha shows two gene loci, one of which is a pseudogene. They are located on different chromosomes...... genetic changes are necessarily involved; the observed changes may be entirely due to a signal transduction pathway where CK-2 could be phosphorylated by another kinase(s). CK-2 cDNAs from various organisms have been isolated and characterized. From the deduced amino acid sequence it turns out that CK-2...

  20. Pharmacological inhibition of Polo Like Kinase 2 (PLK2) does not cause chromosomal damage or result in the formation of micronuclei

    Energy Technology Data Exchange (ETDEWEB)

    Fitzgerald, Kent, E-mail: Kent.fitzgerald@elan.com [Pharmacological Sciences, Elan Pharmaceuticals Inc., 180 Oyster Point Boulevard, South San Francisco, CA 94080 (United States); Bergeron, Marcelle, E-mail: Marcelle.bergeron@elan.com [Pharmacological Sciences, Elan Pharmaceuticals Inc., 180 Oyster Point Boulevard, South San Francisco, CA 94080 (United States); Willits, Christopher, E-mail: Chris.willits@elan.com [Pharmacological Sciences, Elan Pharmaceuticals Inc., 180 Oyster Point Boulevard, South San Francisco, CA 94080 (United States); Bowers, Simeon, E-mail: Simeon.bowers@elan.com [Chemistry, Elan Pharmaceuticals Inc., 180 Oyster Point Boulevard, South San Francisco, CA 94080 (United States); Aubele, Danielle L., E-mail: Danielle.aubele@elan.com [Chemistry, Elan Pharmaceuticals Inc., 180 Oyster Point Boulevard, South San Francisco, CA 94080 (United States); Goldbach, Erich, E-mail: Erich.goldbach@elan.com [Drug Metabolism and Pharmacokinetics, Elan Pharmaceuticals Inc., 180 Oyster Point Boulevard, South San Francisco, CA 94080 (United States); Tonn, George, E-mail: George.tonn@elan.com [Drug Metabolism and Pharmacokinetics, Elan Pharmaceuticals Inc., 180 Oyster Point Boulevard, South San Francisco, CA 94080 (United States); Ness, Daniel, E-mail: Dan.ness@elan.com [Nonclinical Safety Evaluation, Elan Pharmaceuticals Inc., 180 Oyster Point Boulevard, South San Francisco, CA 94080 (United States); Olaharski, Andrew, E-mail: andrew.olaharski@agios.com [Nonclinical Safety Evaluation, Elan Pharmaceuticals Inc., 180 Oyster Point Boulevard, South San Francisco, CA 94080 (United States)

    2013-05-15

    Polo Like Kinase 2 (PLK2) phosphorylates α-synuclein and is considered a putative therapeutic target for Parkinson's disease. Several lines of evidence indicate that PLK2 is involved with proper centriole duplication and cell cycle regulation, inhibition of which could impact chromosomal integrity during mitosis. The objectives of the series of experiments presented herein were to assess whether specific inhibition of PLK2 is genotoxic and determine if PLK2 could be considered a tractable pharmacological target for Parkinson's disease. Several selective PLK2 inhibitors, ELN 582175 and ELN 582646, and their inactive enantiomers, ELN 582176 and ELN 582647, did not significantly increase the number of micronuclei in the in vitro micronucleus assay. ELN 582646 was administered to male Sprague Dawley rats in an exploratory 14-day study where flow cytometric analysis of peripheral blood identified a dose-dependent increase in the number of micronucleated reticulocytes. A follow-up investigative study demonstrated that ELN 582646 administered to PLK2 deficient and wildtype mice significantly increased the number of peripheral micronucleated reticulocytes in both genotypes, suggesting that ELN 582646-induced genotoxicity is not through the inhibition of PLK2. Furthermore, significant reduction of retinal phosphorylated α-synuclein levels was observed at three non-genotoxic doses, additional data to suggest that pharmacological inhibition of PLK2 is not the cause of the observed genotoxicity. These data, in aggregate, indicate that PLK2 inhibition is a tractable CNS pharmacological target that does not cause genotoxicity at doses and exposures that engage the target in the sensory retina. - Highlights: • Active and inactive enantiomers test negative in the in vitro micronucleus test. • ELN 582646 significantly increased micronuclei at 100 and 300 mg/kg/day doses. • ELN 582646 significantly increased micronuclei in PLK2 knockout mice. • ELN 582646

  1. Pharmacological inhibition of Polo Like Kinase 2 (PLK2) does not cause chromosomal damage or result in the formation of micronuclei

    International Nuclear Information System (INIS)

    Polo Like Kinase 2 (PLK2) phosphorylates α-synuclein and is considered a putative therapeutic target for Parkinson's disease. Several lines of evidence indicate that PLK2 is involved with proper centriole duplication and cell cycle regulation, inhibition of which could impact chromosomal integrity during mitosis. The objectives of the series of experiments presented herein were to assess whether specific inhibition of PLK2 is genotoxic and determine if PLK2 could be considered a tractable pharmacological target for Parkinson's disease. Several selective PLK2 inhibitors, ELN 582175 and ELN 582646, and their inactive enantiomers, ELN 582176 and ELN 582647, did not significantly increase the number of micronuclei in the in vitro micronucleus assay. ELN 582646 was administered to male Sprague Dawley rats in an exploratory 14-day study where flow cytometric analysis of peripheral blood identified a dose-dependent increase in the number of micronucleated reticulocytes. A follow-up investigative study demonstrated that ELN 582646 administered to PLK2 deficient and wildtype mice significantly increased the number of peripheral micronucleated reticulocytes in both genotypes, suggesting that ELN 582646-induced genotoxicity is not through the inhibition of PLK2. Furthermore, significant reduction of retinal phosphorylated α-synuclein levels was observed at three non-genotoxic doses, additional data to suggest that pharmacological inhibition of PLK2 is not the cause of the observed genotoxicity. These data, in aggregate, indicate that PLK2 inhibition is a tractable CNS pharmacological target that does not cause genotoxicity at doses and exposures that engage the target in the sensory retina. - Highlights: • Active and inactive enantiomers test negative in the in vitro micronucleus test. • ELN 582646 significantly increased micronuclei at 100 and 300 mg/kg/day doses. • ELN 582646 significantly increased micronuclei in PLK2 knockout mice. • ELN 582646 decreased

  2. Cloning of the Koi Herpesvirus Genome as an Infectious Bacterial Artificial Chromosome Demonstrates That Disruption of the Thymidine Kinase Locus Induces Partial Attenuation in Cyprinus carpio koi▿

    Science.gov (United States)

    Costes, B.; Fournier, G.; Michel, B.; Delforge, C.; Raj, V. Stalin; Dewals, B.; Gillet, L.; Drion, P.; Body, A.; Schynts, F.; Lieffrig, F.; Vanderplasschen, A.

    2008-01-01

    Koi herpesvirus (KHV) is the causative agent of a lethal disease in koi and common carp. In the present study, we describe the cloning of the KHV genome as a stable and infectious bacterial artificial chromosome (BAC) clone that can be used to produce KHV recombinant strains. This goal was achieved by the insertion of a loxP-flanked BAC cassette into the thymidine kinase (TK) locus. This insertion led to a BAC plasmid that was stably maintained in bacteria and was able to regenerate virions when permissive cells were transfected with the plasmid. Reconstituted virions free of the BAC cassette but carrying a disrupted TK locus (the FL BAC-excised strain) were produced by the transfection of Cre recombinase-expressing cells with the BAC. Similarly, virions with a wild-type revertant TK sequence (the FL BAC revertant strain) were produced by the cotransfection of cells with the BAC and a DNA fragment encoding the wild-type TK sequence. Reconstituted recombinant viruses were compared to the wild-type parental virus in vitro and in vivo. The FL BAC revertant strain and the FL BAC-excised strain replicated comparably to the parental FL strain. The FL BAC revertant strain induced KHV infection in koi carp that was indistinguishable from that induced by the parental strain, while the FL BAC-excised strain exhibited a partially attenuated phenotype. Finally, the usefulness of the KHV BAC for recombination studies was demonstrated by the production of an ORF16-deleted strain by using prokaryotic recombination technology. The availability of the KHV BAC is an important advance that will allow the study of viral genes involved in KHV pathogenesis, as well as the production of attenuated recombinant candidate vaccines. PMID:18337580

  3. Silencing expression of the catalytic subunit of DNA-dependent protein kinase by small interfering RNA sensitizes human cells for radiation-induced chromosome damage, cell killing, and mutation

    Science.gov (United States)

    Peng, Yuanlin; Zhang, Qinming; Nagasawa, Hatsumi; Okayasu, Ryuichi; Liber, Howard L.; Bedford, Joel S.

    2002-01-01

    Targeted gene silencing in mammalian cells by RNA interference (RNAi) using small interfering RNAs (siRNAs) was recently described by Elbashir et al. (S. M. Elbashir et al., Nature (Lond.), 411: 494-498, 2001). We have used this methodology in several human cell strains to reduce expression of the Prkdc (DNA-PKcs) gene coding for the catalytic subunit of the DNA-dependent protein kinase (DNA-PKcs) that is involved in the nonhomologous end joining of DNA double-strand breaks. We have also demonstrated a radiosensitization for several phenotypic endpoints of radiation damage. In low-passage normal human fibroblasts, siRNA knock-down of DNA-PKcs resulted in a reduced capacity for restitution of radiation-induced interphase chromosome breaks as measured by premature chromosome condensation, an increased yield of acentric chromosome fragments at the first postirradiation mitosis, and an increased radiosensitivity for cell killing. For three strains of related human lymphoblasts, DNA-PKcs-targeted siRNA transfection resulted in little or no increase in radiosensitivity with respect to cell killing, a 1.5-fold decrease in induced mutant yield in TK6- and p53-null NH32 cells, but about a 2-fold increase in induced mutant yield in p53-mutant WTK1 cells at both the hypoxanthine quanine phosphoribosyl transferase (hprt) and the thymidine kinase loci.

  4. Clinical impact of ABL1 kinase domain mutations and IKZF1 deletion in adults under age 60 with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL): molecular analysis of CALGB (Alliance) 10001 and 9665.

    Science.gov (United States)

    DeBoer, Rebecca; Koval, Gregory; Mulkey, Flora; Wetzler, Meir; Devine, Steven; Marcucci, Guido; Stone, Richard M; Larson, Richard A; Bloomfield, Clara D; Geyer, Susan; Mullighan, Charles G; Stock, Wendy

    2016-10-01

    Recent studies have identified oncogenic lesions in Philadelphia chromosome-positive (Ph+)  acute lymphoblastic leukemia (ALL) and ABL1 kinase mutations that confer resistance to tyrosine kinase inhibitors. We sought to determine the prevalence and clinical impact of these lesions in patients on CALGB 10001, a previously reported Phase II study of imatinib, chemotherapy, and hematopoietic cell transplant in adult Ph + ALL. Of the 58 enrolled, 22 relapsed. By direct sequencing, an ABL1 kinase mutation known to induce imatinib resistance was present at relapse in 13 of 20. Using quantitative PCR assays, the mutations were detectable at diagnosis or early during treatment in most (62%) relapsed patients. Aberrations in IKZF1, CDKN2A/B, and PAX5 were assessed in 28 samples using SNP arrays and genomic DNA sequencing. Of these, 22 (79%) had IKZF1 deletion. The combination of IKZF1 deletion and p210 BCR-ABL1 (p < 0.0001), high white blood cell count (p = 0.021), and minimal residual disease (p = 0.013) were associated with worse disease-free survival. PMID:26892479

  5. Chromosomal mapping and mutational analysis of the coding region of the glycogen synthase kinase-3alpha and beta isoforms in patients with NIDDM

    DEFF Research Database (Denmark)

    Hansen, L; Arden, K C; Rasmussen, S B;

    1997-01-01

    Activation of glycogen synthesis in skeletal muscle in response to insulin results from the combined inactivation of glycogen synthase kinase-3 (GSK-3) and activation of the protein phosphatase-1, changing the ratio between the inactive phosphorylated state of the glycogen synthase to the active ...

  6. Mapping of the receptor protein-tyrosine kinase 10 to human chromosome 1q21-q23 and mouse chromosome 1H1-5 by fluorescence in situ hybridization

    Energy Technology Data Exchange (ETDEWEB)

    Edelhoff, S.; Disteche, C.M. [Univ. of Washington School of Medicine, Seattle, WA (United States); Lai, C. [Scripps Research Inst., LaJolla, CA (United States)

    1995-01-01

    Receptor protein-tyrosine kinases (PTKs) play a critical role in the transduction of signals important to cell growth, differentiation, and survival. Mutations affecting the expression of receptor PTK genes have been associated with a number of vertebrate and invertebrate developmental abnormalities, and the aberrant regulation of tyrosine phosphorylation is implicated in a variety of neoplasias. One estimate suggests that approximately 100 receptor PTK genes exist in the mammalian genome, about half of which have been identified. The tyro-10 receptor protein-tyrosine kinase, first identified in a PCR-based survey for novel tyrosine kinases in the rat nervous system, defines a new subfamily of PTKs. It exhibits a catalytic domain most closely related to those found in the trk PTK receptor subfamily, which transduces signals for nerve growth factor and the related molecules brain-derived neurotrophic factor (BDNF), neurotrophin-3, and neurotrophin-4 (NT-3 and NT-4). Trk and the related PTK receptors trkB and trkC play a critical role in the neurotrophin-dependent survival of subsets of sensory and motor neurons. The predicted tyro-10 extracellular region is, however, distinct from that of the trk subfamily and is unique except for a domain shared with the blood coagulation factors V and VIII, thought to be involved in phospholipid binding. Although tyro-10 RNA is most abundant in heart and skeletal muscle in the adult rat, it is expressed in a wide variety of tissues, including the developing and mature brain. Tyro-10 appears identical to the murine TKT sequence reported by Karn et al. and exhibits a high degree of similarity with the CaK, DDR, and Nep PTKs. A ligand for tyro-10 has not yet been identified. 10 refs., 1 fig.

  7. Nilotinib (formerly AMN107), a highly selective BCR-ABL tyrosine kinase inhibitor, is effective in patients with Philadelphia chromosome-positive chronic myelogenous leukemia in chronic phase following imatinib resistance and intolerance.

    Science.gov (United States)

    Kantarjian, Hagop M; Giles, Francis; Gattermann, Norbert; Bhalla, Kapil; Alimena, Giuliana; Palandri, Francesca; Ossenkoppele, Gert J; Nicolini, Franck-Emmanuel; O'Brien, Stephen G; Litzow, Mark; Bhatia, Ravi; Cervantes, Francisco; Haque, Ariful; Shou, Yaping; Resta, Debra J; Weitzman, Aaron; Hochhaus, Andreas; le Coutre, Philipp

    2007-11-15

    Nilotinib, an orally bioavailable, selective Bcr-Abl tyrosine kinase inhibitor, is 30-fold more potent than imatinib in pre-clinical models, and overcomes most imatinib resistant BCR-ABL mutations. In this phase 2 open-label study, 400 mg nilotinib was administered orally twice daily to 280 patients with Philadelphia chromosome-positive (Ph(+)) chronic myeloid leukemia in chronic phase (CML-CP) after imatinib failure or intolerance. Patients had at least 6 months of follow-up and were evaluated for hematologic and cytogenetic responses, as well as for safety and overall survival. At 6 months, the rate of major cytogenetic response (Ph < or = 35%) was 48%: complete (Ph = 0%) in 31%, and partial (Ph = 1%-35%) in 16%. The estimated survival at 12 months was 95%. Nilotinib was effective in patients harboring BCR-ABL mutations associated with imatinib resistance (except T315I), and also in patients with a resistance mechanism independent of BCR-ABL mutations. Adverse events were mostly mild to moderate, and there was minimal cross-intolerance with imatinib. Grades 3 to 4 neutropenia and thrombocytopenia were observed in 29% of patients; pleural or pericardial effusions were observed in 1% (none were severe). In summary, nilotinib is highly active and safe in patients with CML-CP after imatinib failure or intolerance. This clinical trial is registered at http://clinicaltrials.gov as ID no. NCT00109707. PMID:17715389

  8. Chromosome segregation: learning to let go.

    Science.gov (United States)

    Higgins, Jonathan M G

    2013-10-01

    To ensure accurate chromosome segregation, cohesion between sister chromatids must be released in a controlled manner during mitosis. A new study reveals how distinct centromere populations of the cohesin protector Sgo1 are regulated by microtubule attachments, cyclin-dependent kinases, and the kinetochore kinase Bub1. PMID:24112985

  9. The ATM kinase signaling induced by the low-energy {beta}-particles emitted by {sup 33}P is essential for the suppression of chromosome aberrations and is greater than that induced by the energetic {beta}-particles emitted by {sup 32}P

    Energy Technology Data Exchange (ETDEWEB)

    White, Jason S.; Yue Ning [Department of Radiation Oncology, University of Pittsburgh Medical School, Hillman Cancer Center, Research Pavilion, Suite 2.6, 5117 Centre Avenue, Pittsburgh, PA 15213-1863 (United States); Hu Jing [Department of Pharmacology and Chemical Biology, University of Pittsburgh Medical School, Hillman Cancer Center, Research Pavilion, Suite 2.6, 5117 Centre Avenue, Pittsburgh, PA 15213-1863 (United States); Bakkenist, Christopher J., E-mail: bakkenistcj@upmc.edu [Department of Radiation Oncology, University of Pittsburgh Medical School, Hillman Cancer Center, Research Pavilion, Suite 2.6, 5117 Centre Avenue, Pittsburgh, PA 15213-1863 (United States); Department of Pharmacology and Chemical Biology, University of Pittsburgh Medical School, Hillman Cancer Center, Research Pavilion, Suite 2.6, 5117 Centre Avenue, Pittsburgh, PA 15213-1863 (United States)

    2011-03-15

    Ataxia-telangiectasia mutated (ATM) encodes a nuclear serine/threonine protein kinase whose activity is increased in cells exposed to low doses of ionizing radiation (IR). Here we examine ATM kinase activation in cells exposed to either {sup 32}P- or {sup 33}P-orthophosphate under conditions typically employed in metabolic labelling experiments. We calculate that the absorbed dose of IR delivered to a 5 cm x 5 cm monolayer of cells incubated in 2 ml media containing 1 mCi of the high-energy (1.70 MeV) {beta}-particle emitter {sup 32}P-orthophosphate for 30 min is {approx}1 Gy IR. The absorbed dose of IR following an otherwise identical exposure to the low-energy (0.24 MeV) {beta}-particle emitter {sup 33}P-orthophosphate is {approx}0.18 Gy IR. We show that low-energy {beta}-particles emitted by {sup 33}P induce a greater number of ionizing radiation-induced foci (IRIF) and greater ATM kinase signaling than energetic {beta}-particles emitted by {sup 32}P. Hence, we demonstrate that it is inappropriate to use {sup 33}P-orthophosphate as a negative control for {sup 32}P-orthophosphate in experiments investigating DNA damage responses to DNA double-strand breaks (DSBs). Significantly, we show that ATM accumulates in the chromatin fraction when ATM kinase activity is inhibited during exposure to either radionuclide. Finally, we also show that chromosome aberrations accumulate in cells when ATM kinase activity is inhibited during exposure to {approx}0.36 Gy {beta}-particles emitted by {sup 33}P. We therefore propose that direct cellular exposure to {sup 33}P-orthophosphate is an excellent means to induce and label the IR-induced, ATM kinase-dependent phosphoproteome.

  10. Chromosomal aberration

    International Nuclear Information System (INIS)

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

  11. Synthetic chromosomes.

    Science.gov (United States)

    Schindler, Daniel; Waldminghaus, Torsten

    2015-11-01

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

  12. 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

  13. Rac-1 and Raf-1 kinases, components of distinct signaling pathways, activate myotonic dystrophy protein kinase

    Science.gov (United States)

    Shimizu, M.; Wang, W.; Walch, E. T.; Dunne, P. W.; Epstein, H. F.

    2000-01-01

    Myotonic dystrophy protein kinase (DMPK) is a serine-threonine protein kinase encoded by the myotonic dystrophy (DM) locus on human chromosome 19q13.3. It is a close relative of other kinases that interact with members of the Rho family of small GTPases. We show here that the actin cytoskeleton-linked GTPase Rac-1 binds to DMPK, and coexpression of Rac-1 and DMPK activates its transphosphorylation activity in a GTP-sensitive manner. DMPK can also bind Raf-1 kinase, the Ras-activated molecule of the MAP kinase pathway. Purified Raf-1 kinase phosphorylates and activates DMPK. The interaction of DMPK with these distinct signals suggests that it may play a role as a nexus for cross-talk between their respective pathways and may partially explain the remarkable pleiotropy of DM.

  14. Purification, crystallization and preliminary X-ray diffraction analysis of the kinase domain of human tousled-like kinase 2

    OpenAIRE

    Garrote, Ana M.; Redondo, Pilar; Montoya, Guillermo; Muñoz, Inés G.

    2014-01-01

    Tousled-like kinases (TLKs) are an evolutionarily conserved family of serine/threonine protein kinases involved in chromatin dynamics, including DNA replication and repair, transcription and chromosome segregation. The two members of the family reported in humans, namely TLK1 and TLK2, localize to the cell nucleus and are capable of forming homo- or hetero-oligomers by themselves. To characterize the role of TLK2, its C-terminal kinase domain was cloned and overexpressed in Escherichia coli f...

  15. Kinase signaling in the spindle checkpoint.

    Science.gov (United States)

    Kang, Jungseog; Yu, Hongtao

    2009-06-01

    The spindle checkpoint is a cell cycle surveillance system that ensures the fidelity of chromosome segregation. In mitosis, it elicits the "wait anaphase" signal to inhibit the anaphase-promoting complex or cyclosome until all chromosomes achieve bipolar microtubule attachment and align at the metaphase plate. Because a single kinetochore unattached to microtubules activates the checkpoint, the wait anaphase signal is thought to be generated by this kinetochore and is then amplified and distributed throughout the cell to inhibit the anaphase-promoting complex/cyclosome. Several spindle checkpoint kinases participate in the generation and amplification of this signal. Recent studies have begun to reveal the activation mechanisms of these checkpoint kinases. Increasing evidence also indicates that the checkpoint kinases not only help to generate the wait anaphase signal but also actively correct kinetochore-microtubule attachment defects. PMID:19228686

  16. Mitotic chromosome structure

    International Nuclear Information System (INIS)

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

  17. Cell division control by the Chromosomal Passenger Complex

    Energy Technology Data Exchange (ETDEWEB)

    Waal, Maike S. van der; Hengeveld, Rutger C.C.; Horst, Armando van der; Lens, Susanne M.A., E-mail: s.m.a.lens@umcutrecht.nl

    2012-07-15

    The Chromosomal Passenger Complex (CPC) consisting of Aurora B kinase, INCENP, Survivin and Borealin, is essential for genomic stability by controlling multiple processes during both nuclear and cytoplasmic division. In mitosis it ensures accurate segregation of the duplicated chromosomes by regulating the mitotic checkpoint, destabilizing incorrectly attached spindle microtubules and by promoting the axial shortening of chromosomal arms in anaphase. During cytokinesis the CPC most likely prevents chromosome damage by imposing an abscission delay when a chromosome bridge connects the two daughter cells. Moreover, by controlling proper cytoplasmic division, the CPC averts tetraploidization. This review describes recent insights on how the CPC is capable of conducting its various functions in the dividing cell to ensure chromosomal stability.

  18. Fetal chromosome analysis: screening for chromosome disease?

    DEFF Research Database (Denmark)

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

    1983-01-01

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

  19. Mitotic regulation by NIMA-related kinases

    Directory of Open Access Journals (Sweden)

    Blot Joelle

    2007-08-01

    Full Text Available Abstract The NIMA-related kinases represent a family of serine/threonine kinases implicated in cell cycle control. The founding member of this family, the NIMA kinase of Aspergillus nidulans, as well as the fission yeast homologue Fin1, contribute to multiple aspects of mitotic progression including the timing of mitotic entry, chromatin condensation, spindle organization and cytokinesis. Mammals contain a large family of eleven NIMA-related kinases, named Nek1 to Nek11. Of these, there is now substantial evidence that Nek2, Nek6, Nek7 and Nek9 also regulate mitotic events. At least three of these kinases, as well as NIMA and Fin1, have been localized to the microtubule organizing centre of their respective species, namely the centrosome or spindle pole body. Here, they have important functions in microtubule organization and mitotic spindle assembly. Other Nek kinases have been proposed to play microtubule-dependent roles in non-dividing cells, most notably in regulating the axonemal microtubules of cilia and flagella. In this review, we discuss the evidence that NIMA-related kinases make a significant contribution to the orchestration of mitotic progression and thereby protect cells from chromosome instability. Furthermore, we highlight their potential as novel chemotherapeutic targets.

  20. Diversification of Lrk/Tak Kinase Gene Clusters is Associated with Subfunctionalization and Cultivar-specific Transcript Accumulation in Barley

    Science.gov (United States)

    Lrk (Lr10 receptor-like kinase) and Tak (Triticum aestivum kinase) belong to the receptor-like kinase (RLK) super-gene family in higher plants. Three Lrk/Tak gene regions spanning greater than 600 kb were identified via a genome-wide survey of barley gene-rich BAC (Bacterial Artificial Chromosome) ...

  1. 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

  2. DNA Repair Defects and Chromosomal Aberrations

    Science.gov (United States)

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

    2009-01-01

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

  3. 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)

  4. Polo kinase Cdc5 is a central regulator of meiosis I

    OpenAIRE

    Attner, Michelle A.; Miller, Matthew P.; Ee, Ly-Sha; Elkin, Sheryl K; Amon, Angelika

    2013-01-01

    During meiosis, two consecutive rounds of chromosome segregation yield four haploid gametes from one diploid cell. The Polo kinase Cdc5 is required for meiotic progression, but how Cdc5 coordinates multiple cell-cycle events during meiosis I is not understood. Here we show that CDC5-dependent phosphorylation of Rec8, a subunit of the cohesin complex that links sister chromatids, is required for efficient cohesin removal from chromosome arms, which is a prerequisite for meiosis I chromosome se...

  5. The conserved protein kinase Ipl1 regulates microtubule binding to kinetochores in budding yeast

    OpenAIRE

    Biggins, Sue; Fedor F. Severin; Bhalla, Needhi; Sassoon, Ingrid; Hyman, Anthony A.; Murray, Andrew W.

    1999-01-01

    Chromosome segregation depends on kinetochores, the structures that mediate chromosome attachment to the mitotic spindle. We isolated mutants in IPL1, which encodes a protein kinase, in a screen for budding yeast mutants that have defects in sister chromatid separation and segregation. Cytological tests show that ipl1 mutants can separate sister chromatids but are defective in chromosome segregation. Kinetochores assembled in extracts from ipl1 mutants show altered binding to microtubules. Ip...

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

    Science.gov (United States)

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

    2010-12-15

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

  7. Plant sex chromosome evolution.

    Science.gov (United States)

    Charlesworth, Deborah

    2013-01-01

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

  8. [Dasatinib. A novel tyrosine kinase inhibitor for the treatment of chronic myeloid leukaemia

    DEFF Research Database (Denmark)

    Dufva, I.H.; Stentoft, J.; Hasselbalch, H.C.;

    2008-01-01

    Chronic myeloid leukaemia is characterized by an abnormal tyrosin kinase in the cytoplasm of the clonal cells. The enzyme is derived from a fusion gene on the Philadelphia-chromosome, evolved by a translocation between chromosomes 9 and 22. Understanding the biology of the tyrosin kinase led to t...... targeted therapy, inhibiting the ATP-binding site by a small molecule--imatinib (Glivec). A novel 2nd generation tyrosin kinase inhibitor--dasatinib (Sprycel)--is now available in cases of insufficient response or intolerance to imatinib Udgivelsesdato: 2008/1/28...

  9. Vibrio chromosomes share common history

    OpenAIRE

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

    2010-01-01

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

  10. CK (Creatine Kinase) Test

    Science.gov (United States)

    ... be limited. Home Visit Global Sites Search Help? Creatine Kinase Share this page: Was this page helpful? Also known as: CK; Total CK; Creatine Phosphokinase; CPK Formal name: Creatine Kinase Related tests: ...

  11. 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.

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

    Science.gov (United States)

    Koch, Marcus A

    2015-09-01

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

  13. Phosphorylation of chromosome core components may serve as axis marks for the status of chromosomal events during mammalian meiosis.

    Directory of Open Access Journals (Sweden)

    Tomoyuki Fukuda

    2012-02-01

    Full Text Available Meiotic recombination and chromosome synapsis between homologous chromosomes are essential for proper chromosome segregation at the first meiotic division. While recombination and synapsis, as well as checkpoints that monitor these two events, take place in the context of a prophase I-specific axial chromosome structure, it remains unclear how chromosome axis components contribute to these processes. We show here that many protein components of the meiotic chromosome axis, including SYCP2, SYCP3, HORMAD1, HORMAD2, SMC3, STAG3, and REC8, become post-translationally modified by phosphorylation during the prophase I stage. We found that HORMAD1 and SMC3 are phosphorylated at a consensus site for the ATM/ATR checkpoint kinase and that the phosphorylated forms of HORMAD1 and SMC3 localize preferentially to unsynapsed chromosomal regions where synapsis has not yet occurred, but not to synapsed or desynapsed regions. We investigated the genetic requirements for the phosphorylation events and revealed that the phosphorylation levels of HORMAD1, HORMAD2, and SMC3 are dramatically reduced in the absence of initiation of meiotic recombination, whereas BRCA1 and SYCP3 are required for normal levels of phosphorylation of HORMAD1 and HORMAD2, but not of SMC3. Interestingly, reduced HORMAD1 and HORMAD2 phosphorylation is associated with impaired targeting of the MSUC (meiotic silencing of unsynapsed chromatin machinery to unsynapsed chromosomes, suggesting that these post-translational events contribute to the regulation of the synapsis surveillance system. We propose that modifications of chromosome axis components serve as signals that facilitate chromosomal events including recombination, checkpoint control, transcription, and synapsis regulation.

  14. Glc7/Protein Phosphatase 1 Regulatory Subunits Can Oppose the Ipl1/Aurora Protein Kinase by Redistributing Glc7

    OpenAIRE

    Pinsky, Benjamin A.; Kotwaliwale, Chitra V.; Tatsutani, Sean Y.; Breed, Christopher A.; Biggins, Sue

    2006-01-01

    Faithful chromosome segregation depends on the opposing activities of the budding yeast Glc7/PP1 protein phosphatase and Ipl1/Aurora protein kinase. We explored the relationship between Glc7 and Ipl1 and found that the phosphorylation of the Ipl1 substrate, Dam1, was altered by decreased Glc7 activity, whereas Ipl1 levels, localization, and kinase activity were not. These data strongly suggest that Glc7 ensures accurate chromosome segregation by dephosphorylating Ipl1 targets rather than regu...

  15. 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)

  16. 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

  17. 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.

  18. Chromosome numbers in Bromeliaceae

    OpenAIRE

    2000-01-01

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

  19. 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

  20. Vibrio chromosomes share common history

    Directory of Open Access Journals (Sweden)

    Gevers Dirk

    2010-05-01

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

  1. Mps1 and Ipl1/Aurora B Act Sequentially to Correctly Orient Chromosomes on the Meiotic Spindle of Budding Yeast

    OpenAIRE

    Meyer, Régis E; Kim, Seoyoung; Obeso, David; Straight, Paul D.; Winey, Mark; Dawson, Dean S.

    2013-01-01

    The conserved kinases Mps1 and Ipl1/Aurora B are critical for enabling chromosomes to attach to microtubules such that partner chromosomes will be segregated correctly from each other, but the precise roles of these kinases have been unclear. Here, imaging of live yeast cells was performed to elucidate the stages of chromosome-microtubule interactions, and their regulation by Ipl1 and Mps1, through meiosis I. Ipl1 was found to release kinetochore-microtubule (kMT) associations following meiot...

  2. Basal aurora kinase B activity is sufficient for histone H3 phosphorylation in prophase

    Directory of Open Access Journals (Sweden)

    Ly-Thuy-Tram Le

    2013-02-01

    Histone H3 phosphorylation is the hallmark of mitosis deposited by aurora kinase B. Benzo[e]pyridoindoles are a family of potent, broad, ATP-competitive aurora kinase inhibitors. However, benzo[e]pyridoindole C4 only inhibits histone H3 phosphorylation in prophase but not in metaphase. Under the C4 treatment, the cells enter into mitosis with dephosphorylated histone H3, assemble chromosomes normally and progress to metaphase, and then to anaphase. C4 also induces lagging chromosome in anaphase but we demonstrated that these chromosome compaction defects are not related to the absence of H3 phosphorylation in prophase. As a result of C4 action, mitosis lasts longer and the cell cycle is slowed down. We reproduced the mitotic defects with reduced concentrations of potent pan aurora kinase as well as with a specific aurora B ATP-competitive inhibitor; we therefore propose that histone H3 phosphorylation and anaphase chromosome compaction involve the basal activity of aurora kinase B. Our data suggest that aurora kinase B is progressively activated at mitosis entry and at anaphase onset. The full activation of aurora kinase B by its partners, in prometaphase, induces a shift in the catalytic domain of aurora B that modifies its affinity for ATP. These waves of activation/deactivation of aurora B correspond to different conformations of the chromosomal complex revealed by FRAP. The presence of lagging chromosomes may have deleterious consequences on the daughter cells and, unfortunately, the situation may be encountered in patients receiving treatment with aurora kinase inhibitors.

  3. 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.

  4. 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.

  5. 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.

  6. Ipl1/Aurora B kinase coordinates synaptonemal complex disassembly with cell cycle progression and crossover formation in budding yeast meiosis

    OpenAIRE

    Jordan, Philip; Copsey, Alice; Newnham, Louise; Kolar, E; Lichten, M; Hoffmann, Eva

    2009-01-01

    Several protein kinases collaborate to orchestrate and integrate cellular and chromosomal events at the G2/M transition in both mitotic and meiotic cells. During the G2/M transition in meiosis, this includes the completion of crossover recombination, spindle formation, and synaptonemal complex (SC) breakdown. We identified Ipl1/Aurora B kinase as the main regulator of SC disassembly. Mutants lacking Ipl1 or its kinase activity assemble SCs with normal timing, but fail to dissociate the centra...

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

    Directory of Open Access Journals (Sweden)

    Yerle Martine

    2003-11-01

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

  8. Function and regulation of Aurora/Ipl1p kinase family in cell division

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    During mitosis, the parent cell distributes its genetic materials equally into two daughter cells through chromosome segregation, a complex movements orchestrated by mitotic kinases and its effector proteins.Faithful chromosome segregation and cytokinesis ensure that each daughter cell receives a full copy of genetic materials of parent cell. Defects in these processes can lead to aneuploidy or polyploidy. Aurora/Ipl1p fanily,a class of conserved serine/threonine kinases, plays key roles in chromosome segregation and cytokinesis.This article highlights the function and regulation of Aurora/Ipl1p family in mitosis and provides potential links between aberrant regulation of Aurora/Ipl1p kinases and pathogenesis of human cancer.

  9. Muscle phosphorylase kinase deficiency

    DEFF Research Database (Denmark)

    Preisler, N; Orngreen, M C; Echaniz-Laguna, A; Laforet, P; Lonsdorfer-Wolf, E; Doutreleau, S; Geny, B; Akman, H O; Dimauro, S; Vissing, J

    2012-01-01

    To examine metabolism during exercise in 2 patients with muscle phosphorylase kinase (PHK) deficiency and to further define the phenotype of this rare glycogen storage disease (GSD).......To examine metabolism during exercise in 2 patients with muscle phosphorylase kinase (PHK) deficiency and to further define the phenotype of this rare glycogen storage disease (GSD)....

  10. Ring chromosome 13

    DEFF Research Database (Denmark)

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

    1992-01-01

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

  11. 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…

  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. 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

  14. Chromosome Morphology in Kniphofia.

    Directory of Open Access Journals (Sweden)

    J. M. J de Wet

    1960-12-01

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

  15. 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

  16. Organization of the bacterial chromosome.

    OpenAIRE

    Krawiec, S.; Riley, M

    1990-01-01

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

  17. [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

  18. 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.

  19. 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

  20. 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.

  1. A chemical tool box defines mitotic and interphase roles for Mps1 kinase

    OpenAIRE

    Lan, Weijie; Don W Cleveland

    2010-01-01

    In this issue, three groups (Hewitt et al. 2010. J. Cell Biol. doi:10.1083/jcb.201002133; Maciejowski et al. 2010. J. Cell Biol. doi:10.1083/jcb.201001050; Santaguida et al. 2010. J. Cell Biol. doi:10.1083/jcb.201001036) use chemical inhibitors to analyze the function of the mitotic checkpoint kinase Mps1. These studies demonstrate that Mps1 kinase activity ensures accurate chromosome segregation through its recruitment to kinetochores of mitotic checkpoint proteins, formation of interphase a...

  2. Protein Kinase A in Cancer

    Directory of Open Access Journals (Sweden)

    Antonio Caretta

    2011-02-01

    Full Text Available In the past, many chromosomal and genetic alterations have been examined as possible causes of cancer. However, some tumors do not display a clear molecular and/or genetic signature. Therefore, other cellular processes may be involved in carcinogenesis. Genetic alterations of proteins involved in signal transduction have been extensively studied, for example oncogenes, while modifications in intracellular compartmentalization of these molecules, or changes in the expression of unmodified genes have received less attention. Yet, epigenetic modulation of second messenger systems can deeply modify cellular functioning and in the end may cause instability of many processes, including cell mitosis. It is important to understand the functional meaning of modifications in second messenger intracellular pathways and unravel the role of downstream proteins in the initiation and growth of tumors. Within this framework, the cAMP system has been examined. cAMP is a second messenger involved in regulation of a variety of cellular functions. It acts mainly through its binding to cAMP-activated protein kinases (PKA, that were suggested to participate in the onset and progression of various tumors. PKA may represent a biomarker for tumor detection, identification and staging, and may be a potential target for pharmacological treatment of tumors.

  3. Protein Kinase A in Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Caretta, Antonio; Mucignat-Caretta, Carla, E-mail: carla.mucignat@unipd.it [Department of Human Anatomy and Physiology, University of Padova, Via Marzolo 3, 35131 Padova (Italy)

    2011-02-28

    In the past, many chromosomal and genetic alterations have been examined as possible causes of cancer. However, some tumors do not display a clear molecular and/or genetic signature. Therefore, other cellular processes may be involved in carcinogenesis. Genetic alterations of proteins involved in signal transduction have been extensively studied, for example oncogenes, while modifications in intracellular compartmentalization of these molecules, or changes in the expression of unmodified genes have received less attention. Yet, epigenetic modulation of second messenger systems can deeply modify cellular functioning and in the end may cause instability of many processes, including cell mitosis. It is important to understand the functional meaning of modifications in second messenger intracellular pathways and unravel the role of downstream proteins in the initiation and growth of tumors. Within this framework, the cAMP system has been examined. cAMP is a second messenger involved in regulation of a variety of cellular functions. It acts mainly through its binding to cAMP-activated protein kinases (PKA), that were suggested to participate in the onset and progression of various tumors. PKA may represent a biomarker for tumor detection, identification and staging, and may be a potential target for pharmacological treatment of tumors.

  4. Chromosome 19 International Workshop

    Energy Technology Data Exchange (ETDEWEB)

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

    1993-01-04

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

  5. Pyruvate kinase blood test

    Science.gov (United States)

    ... break down faster than normal, a condition called hemolytic anemia . This test helps diagnose pyruvate kinase deficiency (PKD) . ... Pa: Elsevier Saunders; 2011:chap 32. Gallagher PG. Hemolytic anemias: red cell membrane and metabolic defects In: Goldman ...

  6. Modulation of the Chromatin Phosphoproteome by the Haspin Protein Kinase

    DEFF Research Database (Denmark)

    Maiolica, Alessio; de Medina-Redondo, Maria; Schoof, Erwin;

    2014-01-01

    protein- protein interaction network. We determined the Haspin consensus motif and the co-crystal structure of the kinase with the histone H3 tail. The structure revealed a unique bent substrate binding mode positioning the histone H3 residues Arg2 and Lys4 adjacent to the Haspin phosphorylated threonine......Recent discoveries have highlighted the importance of Haspin kinase activity for the correct positioning of the kinase Aurora B at the centromere. Haspin phosphorylates Thr3 of the histone H3 (H3), which provides a signal for Aurora B to localize to the centromere of mitotic chromosomes. To date......, histone H3 is the only confirmed Haspin substrate. We used a combination of biochemical, pharmacological, and mass spectrometric approaches to study the consequences of Haspin inhibition in mitotic cells. We quantified 3964 phosphorylation sites on chromatin- associated proteins and identified a Haspin...

  7. Molecular fundamentals of chromosomal mutagenesis

    International Nuclear Information System (INIS)

    Precise quantitative correlation between the yield of chromosome structure damages and the yield of DNA damages is shown when comparing data on molecular and cytogenetic investigations carried out in cultural Mammalia cells. As the chromosome structure damage is to be connected with the damage of its carcass structure, then it is natural that DNA damage in loop regions is not to affect considerably the structure, while DNA damage lying on the loop base and connected with the chromosome carcass is to play a determining role in chromosomal mutagenesis. This DNA constitutes 1-2% from the total quantity of nuclear DNA. If one accepts that damages of these regions of DNA are ''hot'' points of chromosomal mutagenesis, then it becomes clear why 1-2% of preparation damages in a cell are realized in chromosome structural damages

  8. Electochemical detection of chromosome translocation

    DEFF Research Database (Denmark)

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

    2014-01-01

    Cytogenetics is a study of the cell structure with a main focus on chromosomes content and their structure. Chromosome abnormalities, such as translocations may cause various genetic disorders and heametological malignancies. Chromosome translocations are structural rearrangements of two...... hybridization approach developed for label-free detection of the chromosome translocations. For specific translocation detection it is necessary to determine that the two DNA sequences forming a derivative chromosome are connected, which is achieved by two subsequent hybridization steps. The electrochemical...... impedance spectroscopy was selected as the sensing method on a microfabricated chip with array of 12 electrode sets. Two independent chips (Chip1 and Chip2) were used for targeting the chromosomal fragments involved in the translocation. Each chip was differentially functionalized with DNA probes matching...

  9. 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.

  10. Reference-assisted chromosome assembly

    OpenAIRE

    Kim, Jaebum; Larkin, Denis M; Cai, Qingle; Asan,; Zhang, Yongfen; Ge, Ri-Li; Auvil, Loretta; Capitanu, Boris; Zhang, Guojie; Lewin, Harris A.; Ma, Jian

    2013-01-01

    One of the most difficult problems in modern genomics is the assembly of full-length chromosomes using next generation sequencing (NGS) data. To address this problem, we developed “reference-assisted chromosome assembly” (RACA), an algorithm to reliably order and orient sequence scaffolds generated by NGS and assemblers into longer chromosomal fragments using comparative genome information and paired-end reads. Evaluation of results using simulated and real genome assemblies indicates that ou...

  11. 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…

  12. 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

  13. Chromosome analysis and sorting

    Czech Academy of Sciences Publication Activity Database

    Doležel, Jaroslav; Kubaláková, Marie; Suchánková, Pavla; Kovářová, Pavlína; Bartoš, Jan; Šimková, Hana

    Weinheim : Wiley-VCH, 2007 - (Doležel, J.; Greilhuber, J.; Suda, J.), s. 373-403 ISBN 978-3-527-31487-4 R&D Projects: GA ČR GA521/04/0607; GA ČR GP521/05/P257; GA ČR GD521/05/H013; GA MŠk(CZ) LC06004 Grant ostatní: Mendelova zemědělská a lesnická univerzita v Brně / Agronomická fakulta(CZ) ME 844 Institutional research plan: CEZ:AV0Z5038910 Source of funding: V - iné verejné zdroje ; V - iné verejné zdroje ; V - iné verejné zdroje ; V - iné verejné zdroje ; V - iné verejné zdroje Keywords : Plant flow cytometry * chromosome sorting * flow cytogenetics Subject RIV: EB - Genetics ; Molecular Biology http://books. google .com/books?id=3cwakORieqUC&pg=PA373&lpg=PA373&dq=Chromosome+analysis+and+sorting&source=web&ots=8IyvJlBQyq&sig=_NlXyQQgBCwpj1pTC9YITvvVZqU

  14. From Phosphosites to Kinases

    DEFF Research Database (Denmark)

    Munk, Stephanie; Refsgaard, Jan C; Olsen, Jesper V;

    2016-01-01

    Kinases play a pivotal role in propagating the phosphorylation-mediated signaling networks in living cells. With the overwhelming quantities of phosphoproteomics data being generated, the number of identified phosphorylation sites (phosphosites) is ever increasing. Often, proteomics investigations...... sequence motifs, mostly based on large scale in vivo and in vitro experiments. The context of the kinase and the phosphorylated proteins in a biological system is equally important for predicting association between the enzymes and substrates, an aspect that is also being tackled with available...

  15. Phosphatidylinositol kinase from rabbit reticulocytes

    International Nuclear Information System (INIS)

    Phosphatidylinositol (PI) kinase was isolated from the postribosomal supernatant of rabbit reticulocytes. This activity was identified by the formation of a product that comigrated with phosphatidylinositol-4-phosphate (PIP) when purified PI was phosphorylated in the presence of [32P]ATP and Mg2+. Three major peaks of PI kinase activity were resolved by chromatography on DEAE-cellulose. The first peak eluted at 50-100 mM NaCl together with several serine protein kinases, casein kinase (CK) I and protease activated kinase (PAK) I and II. The PI kinase was subsequently separated from the protein kinases by chromatography on phosphocellulose. The second peak eluted at 125-160 mM NaCl and contained another lipid kinase activity that produced a product which comigrated with phosphatidic acid on thin layer chromatography. The third peak, which eluted at 165-200 mM NaCl, partly comigrated with casein kinase (CK) II and an active protein kinase(s) which phosphorylated mixed histone and histone I. CK II and the histone kinase activities were also separated by chromatography on phosphocelluslose. The different forms of PI kinase were characterized and compared with respect to substrate and salt requirements

  16. 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.

  17. 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...

  18. Activation of an enhancerless gene by chromosomal integration.

    OpenAIRE

    Hamada, H

    1986-01-01

    Expression of enhancerless (E-) and enhancer-containing (E+) genes that are chromosomally integrated was examined. An E- plasmid (pE-cat) containing a chloramphenicol acetyltransferase (cat) gene linked to the simian virus 40 (SV40) early promoter or its E+ counterpart plasmid (pE+-cat) containing the SV40 enhancer was cotransfected into thymidine kinase (TK)-deficient L cells with a cloned tk gene. A number of TK+ transformants were isolated, and expression of the cointegrated cat gene in th...

  19. 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 ...

  20. 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 ...

  1. 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

  2. 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...

  3. 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

  4. Kinase Inhibitors from Marine Sponges

    Directory of Open Access Journals (Sweden)

    Ana Zivanovic

    2011-10-01

    Full Text Available Protein kinases play a critical role in cell regulation and their deregulation is a contributing factor in an increasing list of diseases including cancer. Marine sponges have yielded over 70 novel compounds to date that exhibit significant inhibitory activity towards a range of protein kinases. These compounds, which belong to diverse structural classes, are reviewed herein, and ordered based upon the kinase that they inhibit. Relevant synthetic studies on the marine natural product kinase inhibitors have also been included.

  5. Purification, crystallization and preliminary X-ray diffraction analysis of the kinase domain of human tousled-like kinase 2

    International Nuclear Information System (INIS)

    The C-terminal kinase domain of TLK2 (a human tousled-like kinase) has been cloned and overexpressed in Escherichia coli followed by purification to homogeneity. Crystallization experiments in the presence of ATP-γ-S yielded crystals suitable for X-ray diffraction analysis belonging to two different space groups: tetragonal I4122 and cubic P213. Tousled-like kinases (TLKs) are an evolutionarily conserved family of serine/threonine protein kinases involved in chromatin dynamics, including DNA replication and repair, transcription and chromosome segregation. The two members of the family reported in humans, namely TLK1 and TLK2, localize to the cell nucleus and are capable of forming homo- or hetero-oligomers by themselves. To characterize the role of TLK2, its C-terminal kinase domain was cloned and overexpressed in Escherichia coli followed by purification to homogeneity. Crystallization experiments in the presence of ATP-γ-S yielded crystals suitable for X-ray diffraction analysis belonging to two different space groups: tetragonal I4122 and cubic P213. The latter produced the best diffracting crystal (3.4 Å resolution using synchrotron radiation), with unit-cell parameters a = b = c = 126.05 Å, α = β = γ = 90°. The asymmetric unit contained one protein molecule, with a Matthews coefficient of 4.59 Å3 Da−1 and a solvent content of 73.23%

  6. 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...

  7. 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...

  8. 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

  9. Mitotic chromosome condensation in vertebrates

    International Nuclear Information System (INIS)

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

  10. Identification of a BET family Bromodomain / Casein Kinase II / TAF-containing complex as a regulator of mitotic condensin function

    OpenAIRE

    Kim, Hyun-Soo; Mukhopadhyay, Rituparna; Rothbart, Scott B.; Silva, Andrea C.; Vanoosthuyse, Vincent; Radovani, Ernest; Kislinger, Thomas; Roguev, Assen; Ryan, Colm J.; Xu, Jiewei; Jahari, Harlizawati; Hardwick, Kevin G.; Greenblatt, Jack F.; Krogan, Nevan J.; Fillingham, Jeffrey S.

    2014-01-01

    Condensin is a central regulator of mitotic genome structure, with mutants showing poorly condensed chromosomes and profound segregation defects. Here we identify NCT complex, comprising the Nrc1 BET-family tandem bromodomain protein (SPAC631.02), Casein Kinase II (CKII) and several TAFs, as a regulator of condensin function. We show that NCT and condensin bind similar genomic regions, but only briefly co-localize during the periods of chromosome condensation and decondensation. This pattern ...

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

    Directory of Open Access Journals (Sweden)

    Williams Briana

    2003-10-01

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

  12. 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

  13. Chromosome conservation in squamate reptiles revealed by comparative chromosome painting

    Czech Academy of Sciences Publication Activity Database

    Giovannotti, M.; Pokorná, Martina; Kratochvíl, L.; Caputo, V.; Olmo, E.; Ferguson-Smith, M. A.; Rens, W.

    Manchester : ICCS, 2011. 78-78. [Intarnational Chromosome Conference /18./. 29.08.2011-02.09.2011, Manchester] Institutional research plan: CEZ:AV0Z50450515 Keywords : squamate reptiles Subject RIV: EG - Zoology

  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. Tyrosine kinases in rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Kobayashi Akiko

    2011-08-01

    Full Text Available Abstract Rheumatoid arthritis (RA is an inflammatory, polyarticular joint disease. A number of cellular responses are involved in the pathogenesis of rheumatoid arthritis, including activation of inflammatory cells and cytokine expression. The cellular responses involved in each of these processes depends on the specific signaling pathways that are activated; many of which include protein tyrosine kinases. These pathways include the mitogen-activated protein kinase pathway, Janus kinases/signal transducers and activators transcription pathway, spleen tyrosine kinase signaling, and the nuclear factor κ-light-chain-enhancer of activated B cells pathway. Many drugs are in development to target tyrosine kinases for the treatment of RA. Based on the number of recently published studies, this manuscript reviews the role of tyrosine kinases in the pathogenesis of RA and the potential role of kinase inhibitors as new therapeutic strategies of RA.

  17. 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

  18. Cloning of a human galactokinase gene (GK2) on chromosome 15 by complementation in yeast.

    OpenAIRE

    Lee, R T; Peterson, C L; Calman, A F; Herskowitz, I.; O'Donnell, J J

    1992-01-01

    A human cDNA encoding a galactokinase (EC 2.7.1.6) was isolated by complementation of a galactokinase-deficient (gal1-) strain of Saccharomyces cerevisiae. This cDNA encodes a predicted protein of 458 amino acids with 29% identity to galactokinase of Saccharomyces carlsbergensis. Previous studies have mapped a human galactokinase gene (GK1) to chromosome 17q23-25, closely linked to thymidine kinase. The galactokinase gene that we have isolated (GK2) is located on chromosome 15. The relationsh...

  19. Oncoprotein protein kinase

    Energy Technology Data Exchange (ETDEWEB)

    Karin, Michael (San Diego, CA); Hibi, Masahiko (San Diego, CA); Lin, Anning (La Jolla, CA); Davis, Roger (Princeton, MA); Derijard, Benoit (Shrewsbury, MA)

    2003-02-04

    An isolated polypeptide (JNK) characterized by having a molecular weight of 46kD as determined by reducing SDS-PAGE, having serine and threonine kinase activity, phosphorylating the c-Jun N-terminal activation domain and polynucleotide sequences and method of detection of JNK are provided herein. JNK phosphorylates c-Jun N-terminal activation domain which affects gene expression from AP-1 sites.

  20. Kinase-Catalyzed Biotinylation

    OpenAIRE

    Senevirathne, Chamara; Green, Keith D.; Pflum, Mary Kay H.

    2012-01-01

    Kinase-catalyzed protein phosphorylation plays an essential role in a variety of biological processes. Methods to detect phosphoproteins and phosphopeptides in cellular mixtures will aid in cell biological and signaling research. Our laboratory recently discovered the utility of γ-modified ATP analogues as tools for studying phosphorylation. Specifically, ATP-biotin can be used for labeling and visualizing phosphoproteins from cell lysates. Because the biotin tag is suitable for protein detec...

  1. Chromosome fragility in Freemartin cattle

    Directory of Open Access Journals (Sweden)

    V. Barbieri

    2010-04-01

    Full Text Available The aim of the present study was to verify chromosome fragility in freemartin cattle using chromosome aberration (CA and sister chromatid exchange (SCE tests. A total of eighteen co-twins were investigated. Fourteen animals were identified as cytogenetically chimeric (2n=60, XX/XY while 4 were classified as normal. Freemartin cattle showed a higher percentage of aneuploid cells (18.64% and highly significant statistical differences (P < 0.001 in mean values of gaps (4.53 ± 2.05, chromatid breaks (0.26 ± 0.51, and significant statistical differences (P < 0.005 in mean values of chromosome breaks (0.12 ± 0.43 when compared to 10 control animals from single births (aneuploid cells, 11.20%; gaps, 2.01 ± 1.42; chromatid breaks, 0.05 ± 0.22; chromosome breaks, 0.02 ± 0.14.

  2. 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.

  3. 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...

  4. 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...

  5. ABNORMAL PROTEIN TYROSINE KINASES ASSOCIATED WITH HUMAN HAEMATOLOGICAL MALIGNANCIES

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Objective: To survey the role of protein tyrosine kinases (PTKs) in the pathogenesis of several hematopoietic malignancies. Methods: By reviewing the published laboratory and clinical studies on PTK-related oncoproteins and their causative role in some leukemias and lymphomas. Results: Protein tyrosine kinases are key participants in signal transduction pathways that regulate cellular growth, activation and differentiations. Aberrant PTK activity resulting from gene mutation (often accompanying chromosome translocation) plays an etiologic role in several clonal hematopoietic malignancies. For example, the PTK product of the BCR-ABL fusion gene resulting from the t (9; 22) translocation exhibits several fold higher tyrosine kinase activity than the product of the ABL gene. Evidence suggests that the BCR-ABL oncoprotein alone is sufficient to case chronic myelogenous leukemia (CML) and other Ph positive acute leukemia. PTK over-activity resulting from chromosomal translocations creating TEL-ABL, TEL-JAK2 and TEL-PDGFR( fusion proteins plays an important role in the pathogenesis of other types of leukemia. Another example occurs in anaplastic large cell lymphoma (ALCL). Experimental and clinical evidences indicate that translocations involving ALK gene on chromosome 2p23, most commonly resulting in an NPM-ALK fusion oncogene, result in constitutive activation of ALK and cause ALCL. This group of lymphomas is now named ALK positive lymphoma or ALKoma. Conclusion: Genetic lesions creating aberrant fusion proteins that result in excessive PTK activity are increasingly being recognized as central to the pathogenesis of hemotopoietic malignancies. These chimeric PTK molecules represent attractive disease-specific targets against which new classes therapeutic agents are being developed.

  6. 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.

  7. 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

  8. Chromosome Architecture and Genome Organization

    Science.gov (United States)

    Bernardi, Giorgio

    2015-01-01

    How the same DNA sequences can function in the three-dimensional architecture of interphase nucleus, fold in the very compact structure of metaphase chromosomes and go precisely back to the original interphase architecture in the following cell cycle remains an unresolved question to this day. The strategy used to address this issue was to analyze the correlations between chromosome architecture and the compositional patterns of DNA sequences spanning a size range from a few hundreds to a few thousands Kilobases. This is a critical range that encompasses isochores, interphase chromatin domains and boundaries, and chromosomal bands. The solution rests on the following key points: 1) the transition from the looped domains and sub-domains of interphase chromatin to the 30-nm fiber loops of early prophase chromosomes goes through the unfolding into an extended chromatin structure (probably a 10-nm “beads-on-a-string” structure); 2) the architectural proteins of interphase chromatin, such as CTCF and cohesin sub-units, are retained in mitosis and are part of the discontinuous protein scaffold of mitotic chromosomes; 3) the conservation of the link between architectural proteins and their binding sites on DNA through the cell cycle explains the “mitotic memory” of interphase architecture and the reversibility of the interphase to mitosis process. The results presented here also lead to a general conclusion which concerns the existence of correlations between the isochore organization of the genome and the architecture of chromosomes from interphase to metaphase. PMID:26619076

  9. Regulation of Autophagy by Kinases

    International Nuclear Information System (INIS)

    Autophagy is a process of self-degradation that maintains cellular viability during periods of metabolic stress. Although autophagy is considered a survival mechanism when faced with cellular stress, extensive autophagy can also lead to cell death. Aberrations in autophagy are associated with several diseases, including cancer. Therapeutic exploitation of this process requires a clear understanding of its regulation. Although the core molecular components involved in the execution of autophagy are well studied there is limited information on how cellular signaling pathways, particularly kinases, regulate this complex process. Protein kinases are integral to the autophagy process. Atg1, the first autophagy-related protein identified, is a serine/threonine kinase and it is regulated by another serine/threonine kinase mTOR. Emerging studies suggest the participation of many different kinases in regulating various components/steps of this catabolic process. This review focuses on the regulation of autophagy by several kinases with particular emphasis on serine/threonine protein kinases such as mTOR, AMP-activated protein kinase, Akt, mitogen-activated protein kinase (ERK, p38 and JNK) and protein kinase C that are often deregulated in cancer and are important therapeutic targets

  10. The dawn of Aurora kinase research: from fly genetics to the clinic.

    Directory of Open Access Journals (Sweden)

    Mar eCarmena

    2015-11-01

    Full Text Available Aurora kinases comprise a family of highly conserved serine-threonine protein kinases that play a pivotal role in the regulation of cell cycle. Aurora kinases are not only involved in the control of multiple processes during cell division but also coordinate chromosomal and cytoskeletal events, contributing to the regulation of checkpoints and ensuring the smooth progression of the cell cycle.Because of their fundamental contribution to cell cycle regulation, Aurora kinases were originally identified in independent genetic screens designed to find genes involved in the regulation of cell division. The first aurora mutant was part of a collection of mutants isolated in C. Nusslein-Volhard’s laboratory. This collection was screened in D. M. Glover’s laboratory in search for mutations disrupting the centrosome cycle in embryos derived from homozygous mutant mothers. The mutants identified were given names related to the polar regions, and included not only aurora but also the equally famous polo. Ipl1, the only Aurora in yeast, was identified in a genetic screen looking for mutations that caused chromosome segregation defects. The discovery of a second Aurora-like kinase in mammals opened a new chapter in the research of Aurora kinases. The rat kinase AIM was found to be highly homologous to the fly and yeast proteins, but localised at the midzone and midbody and was proposed to have a role in cytokinesis. Homologs of the equatorial Aurora (Aurora B were identified in metazoans ranging from flies to humans. Xenopus Aurora B was found to be in a complex with the chromosomal passenger INCENP, and both proteins were shown to be essential in flies for chromosome structure, segregation, central spindle formation and cytokinesis. Fifteen years on, Aurora kinase research is an active field of research. After the successful introduction of the first anti-mitotic agents in cancer therapy, both Auroras have become the focus of attention as targets for

  11. 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...

  12. Function and interaction of maturation-promoting factor and mitogen-activated protein kinase during meiotic maturation and fertilization of oocyte

    Institute of Scientific and Technical Information of China (English)

    HUO Lijun; FAN Hengyu; CHEN Dayuan; SUN Qingyuan

    2004-01-01

    Mitogen-activated protein kinase (MAP kinase) cascade and maturation-promoting factor (MPF) play very important roles during meiotic maturation and fertilization of oocyte. Interaction between MAP kinase and MPF influences meiotic maturation and fertilization of oocyte throughout the animal kingdom, including stimulation of germinal vesicle breakdown (GVBD), suppression of DNA replication, control of meiotic chromosome segregation, maintenance of metaphase II arrest, and resumption and completion of second meiosis. This review focuses on the function and interaction of MAP kinase and MPF during meiotic maturation and fertilization of oocyte.

  13. Molecular cloning and characterization of a novel human kinase gene, PDIK1L

    Indian Academy of Sciences (India)

    Lingchen Guo; Chaoneng Ji; Shaohua Gu; Kang Ying; Haipeng Cheng; Xiaoghua Ni; Jianping Liu; Yi Xie; Yumin Mao

    2003-04-01

    We isolated a 4301-bp cDNA from a human foetal brain cDNA library by high-throughput cDNA sequencing. It encodes a protein of 341 amino acids, which shows 69% identity with the human kinase CLIK1 (AAL99353), which was suggested to be the CLP-36 interacting kinase. Bioinformatics analysis suggests that the putative kinase may interact with PDZ and LIM domain proteins. Therefore the protein and its cDNA were named ‘PDLIM1 interacting kinase 1 like’ (PDIK1L; nomenclature approved by the HUGO Gene Nomenclature Committee). Ensembl Genome Browser located PDIK1L to human chromosome 1p35.3. It spans about 13.7 kb and consists of four exons and three introns. Multiple-tissue cDNA panel PCR revealed that the gene is expressed widely in human tissues: liver, kidney, pancreas, spleen, thymus and prostate. The protein appears to be localized to the nucleus.

  14. The Ste locus, a component of the parasitic cry-Ste system of Drosophila melanogaster, encodes a protein that forms crystals in primary spermatocytes and mimics properties of the beta subunit of casein kinase 2

    DEFF Research Database (Denmark)

    Bozzetti, M P; Massari, S; Finelli, P; Meggio, F; Pinna, L A; Boldyreff, B; Issinger, O G; Palumbo, G; Ciriaco, C; Bonaccorsi, S

    1995-01-01

    Males of Drosophila melanogaster lacking the Y chromosome-linked crystal locus show multiple meiotic alterations including chromosome disorganization and prominent crystal formation in primary spermatocytes. These alterations are due to the derepression of the X chromosome-linked Stellate sequenc...... is a major component of the crystals. Moreover, in vitro experiments have shown that this protein can interact with the catalytic alpha subunit of casein kinase 2 enzyme, altering its activity....

  15. Bacterial Protein-Tyrosine Kinases

    DEFF Research Database (Denmark)

    Shi, Lei; Kobir, Ahasanul; Jers, Carsten;

    2010-01-01

    Bacteria and Eukarya share essentially the same family of protein-serine/threonine kinases, also known as the Hanks-type kinases. However, when it comes to protein-tyrosine phosphorylation, bacteria seem to have gone their own way. Bacterial protein-tyrosine kinases (BY-kinases) are bacterial...... enzymes that are unique in exploiting the ATP/GTP-binding Walker motif to catalyze phosphorylation of protein tyrosine residues. Characterized for the first time only a decade ago, BY-kinases have now come to the fore. Important regulatory roles have been linked with these enzymes, via their involvement...... in exopolysaccharide production, virulence, DNA metabolism, stress response and other key functions of the bacterial cell. BY-kinases act through autophosphorylation (mainly in exopolysaccharide production) and phosphorylation of other proteins, which have in most cases been shown to be activated by...

  16. Therapeutic targeting of Janus kinases

    OpenAIRE

    Pesu, Marko; Laurence, Arian; Kishore, Nandini; Zwillich, Sam; Chan, Gary; O’Shea, John J.

    2008-01-01

    Cytokines play pivotal roles in immunity and inflammation, and targeting cytokines and their receptors is an effective means of treating such disorders. Type I and II cytokine receptors associate with Janus family kinases (JAKs) to effect intracellular signaling. These structurally unique protein kinases play essential and specific roles in immune cell development and function. One JAK, JAK3, has particularly selective functions. Mutations of this kinase underlie severe combined immunodeficie...

  17. Visualizing autophosphorylation in histidine kinases

    OpenAIRE

    Casino, Patricia; Miguel-Romero, Laura; Marina, Alberto

    2014-01-01

    Reversible protein phosphorylation is the most widespread regulatory mechanism in signal transduction. Autophosphorylation in a dimeric sensor histidine kinase is the first step in two-component signalling, the predominant signal-transduction device in bacteria. Despite being the most abundant sensor kinases in nature, the molecular bases of the histidine kinase autophosphorylation mechanism are still unknown. Furthermore, it has been demonstrated that autophosphorylation can occur in two dir...

  18. Tau-tubulin kinase

    Directory of Open Access Journals (Sweden)

    Seiko Ikezu

    2014-04-01

    Full Text Available Tau-tubulin kinase (TTBK belongs to casein kinase superfamily and can phosphorylate microtubule-associated protein tau and tubulin. TTBK has two isoforms, TTBK1 and TTBK2, which contain highly homologous catalytic domains but their non-catalytic domains are distinctly different. TTBK1 is expressed specifically in the central nervous system and is involved in phosphorylation and aggregation of tau. TTBK2 is ubiquitously expressed in multiple tissues and genetically linked to spinocerebellar ataxia type 11. TTBK1 directly phosphorylates tau protein, especially at Ser422, and also activates cycline-dependent kinase 5 in a unique mechanism. TTBK1 protein expression is significantly elevated in Alzheimer’s disease brains, and genetic variations of the TTBK1 gene are associated with late-onset Alzheimer’s disease in two cohorts of Chinese and Spanish populations. TTBK1 transgenic mice harboring the entire 55-kilobase genomic sequence of human TTBK1 show progression of tau accumulation, neuroinflammation, and neurodegeneration when crossed with tau mutant mice. Our recent study shows that there is a striking switch in mononuclear phagocyte and activation phenotypes in the anterior horn of the spinal cord from alternatively activated (M2-skewed microglia to pro-inflammatory (M1-skewed infiltrating peripheral monocytes in P301L tau mutant mice by crossing with TTBK1 transgenic mice. TTBK1 is responsible for mediating M1-activated microglia-induced neurotoxicity, and its overexpression induces axonal degeneration in vitro. These studies suggest that TTBK1 is an important molecule for the inflammatory axonal degeneration, which may be relevant to the pathobiology of tauopathy including Alzheimer’s disease.

  19. Sgo1 Regulates Both Condensin and Ipl1/Aurora B to Promote Chromosome Biorientation

    OpenAIRE

    Peplowska, K.; Wallek, A.; Storchova, Z.

    2014-01-01

    Correct chromosome segregation is essential in order to prevent aneuploidy. To segregate sister chromatids equally to daughter cells, the sisters must attach to microtubules emanating from opposite spindle poles. This so-called biorientation manifests itself by increased tension and conformational changes across kinetochores and pericentric chromatin. Tensionless attachments are dissolved by the activity of the conserved mitotic kinase Aurora B/Ipl1, thereby promoting the formation of correct...

  20. The role of ATM in chromosome end protection in Arabidopsis thaliana

    Czech Academy of Sciences Publication Activity Database

    Široký, Jiří; Mokroš, Petr; Vespa, L.; Shippen, D.

    2007-01-01

    Roč. 15, č. 20 (2007), s. 51-52. ISSN 0967-3849. [16th International Chromosome Conference. 25.08.2007-29.08.2007, Amsterdam] R&D Projects: GA ČR(CZ) GA522/06/0380 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : telomeres * Arabidopsis * ATM protein kinase Subject RIV: BO - Biophysics

  1. Phosphatidylinositol 3-kinase in myogenesis.

    Science.gov (United States)

    Kaliman, P; Zorzano, A

    1997-08-01

    Phosphatidylinositol 3-kinase (PI 3-kinase) has been cloned and characterized in a wide range of organisms. PI 3-kinases are activated by a diversity of extracellular stimuli and are involved in multiple cell processes such as cell proliferation, protein trafficking, cell motility, differentiation, regulation of cytoskeletal structure, and apoptosis. It has recently been shown that PI 3-kinase is a crucial second messenger in the signaling of myogenesis. Two structurally unrelated highly specific inhibitors of PI 3-kinase-wortmannin and LY294002-block the morphological and biochemical differentiation program of different skeletal-muscle cell models. Moreover, L6E9 myoblasts overexpressing a dominant-negative mutant of PI 3-kinase p85 regulatory subunit (Δp85) are unable to differentiate. Furthermore, PI 3-kinase is specifically involved in the insulinlike growth factor (IGF)-dependent myogenic pathway. Indeed, the ability of IGF-I, des-1,3-IGF-I, and IGF-II to promote cell fusion and muscle-specific protein expression is impaired after treatment with PI 3-kinase inhibitors or in cells overexpressing Δp85. The identification of additional key downstream elements of the IGF/PI 3-kinase myogenic cascade is crucial to a detailed understanding of the process of muscle differentiation and may generate new tools for skeletal and cardiac muscle regeneration therapies. (Trends Cardiovasc Med 1997;7:198-202). © 1997, Elsevier Science Inc. PMID:21235885

  2. Retrospective dosimetry using chromosome painting

    International Nuclear Information System (INIS)

    Chromosome aberration frequency measured in peripheral lymphocytes of persons exposed to ionizing radiation has been used since 1960s for dose assessment. Suspected overexposure is usually evaluated by the frequency of dicentrics and centric rings using an appropriate in vitro calibration curve. However, these chromosome aberrations are unstable with time after exposure and dose reconstruction may encounter uncertainties when the time between the exposure and the analysis is considerable or even unknown. It appears that translocations persist with time after exposure and may be used as an indication of acute past overexposures. Moreover, they appear to accumulate the cytogenetical information, which correlates with the dose received under fractionated, chronic or even occupational exposure conditions. Translocations may be detected using G-banding, which allows to score the total amount of radiation induced translocations but it is a time consuming method, or by Chromosome Painting, a method base on the Fluorescence in situ Hybridization (FISH) technique, painting only some chromosome pairs with specific whole chromosome probes and then extrapolating the observed translocation frequencies to the full genome. The latter method allows a faster aberration scoring than G-banding and appears to be the most promissory tool for biodosimetry, particularly when it is necessary to assess low doses and consequently to score a large number of metaphases, e.g. radiation workers exposed within dose limits. As with the unstable chromosome aberration, it is necessary an in vitro calibration curve based on the frequency of stable chromosome aberrations to assess doses. Our laboratory performed calibration curves for Co60 γ-rays based on the frequencies of unstable (dicentrics and centric rings detected by conventional Giemsa staining) and stable chromosome aberrations (translocations and inversions, detected by G-banding). In order to minimize the interlaboratory variability, we

  3. 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 ...

  4. 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.

  5. 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.)

  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. Chromosomal rearrangement interferes with meiotic X chromosome inactivation

    Czech Academy of Sciences Publication Activity Database

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

    2007-01-01

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

  8. Escape Artists of the X Chromosome.

    Science.gov (United States)

    Balaton, Bradley P; Brown, Carolyn J

    2016-06-01

    Inactivation of one X chromosome in mammalian females achieves dosage compensation between XX females and XY males; however, over 15% of human X-linked genes continue to be expressed from the inactive X chromosome. New genomic methodologies have improved our identification and characterization of these escape genes, revealing the importance of DNA sequence, chromatin structure, and chromosome ultrastructure in regulating expression from an otherwise inactive chromosome. Study of these exceptions to the rule of silencing highlights the interconnectedness of chromatin and chromosome structure in X-chromosome inactivation (XCI). Recent advances also demonstrate the importance of these genes in sexually dimorphic disease risk, particularly cancer. PMID:27103486

  9. 酪氨酸激酶抑制剂联合异基因造血干细胞移植治疗费城染色体阳性急性淋巴细胞白血病的研究进展%Research progress of tyrosine kinase inhibitor combining with allogeneic hematopoietic stem cell transplantation in treatment of Philadelphia chromosome positive acute lymphoblastic leukemia

    Institute of Scientific and Technical Information of China (English)

    王静静; 江明

    2016-01-01

    费城染色体阳性(Ph+)急性淋巴细胞白血病(ALL)是成年人ALL的常见类型.在酪氨酸激酶抑制剂(TKI)问世前,ph+是成年人ALL的不良预后因素之一.在TKI应用于Ph+ ALL治疗后显著改善其疗效,完全缓解(CR)率可达90%以上,缓解持续时间较前明显延长,从而使更多Ph+ ALL患者能够行异基因造血干细胞移植(allo-HSCT).采用以TKI为基础化疗获得CR后行allo-HSCT是Ph+ ALL患者的标准治疗方案.目前,移植前微小残留疾病(MRD)检测是否对该病的治疗具有临床指导意义,尚存争议.替代供者移植治疗Ph+ ALL在临床取得理想疗效,但需要前瞻性随机对照试验来证实其疗效.移植后联合TKI治疗可明显改善Ph+ ALL患者的长期生存,但其具体使用方案仍需多中心、大样本量的临床随机对照实验证实,而移植后复发仍是Ph+ ALL患者面临的难题之一.%Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) is the most common type of adult acute lymphoblastic leukemia(ALL).Before the advent of tyrosine kinase inhibitors (TKI),Ph+ ALL carried a dismal prognosis.Outcomes for patients with Ph+ ALL improved substantially with the administration of TKI,and the TKI induced complete remissions(CR) in more than 90% patients,with remission duration prolonging,making more patients able to undergo allogeneic hematopoietic stem cell transplantation(allo-HSCT).Currently,TKI-based chemotherapy following allo-HSCT is established as the first-line strategy.Breakpoint cluster region-abelson leukemia virus(BCR-ABL) monitoring appears to relate to prognostic relevance and may be as guiding treatment before allo-HSCT,but clinical benefit is controversial in the TKI era.Alternative donor transplantation obtains promising effect in clinical practice,but needs more research.The administration of TKI after allo-HSCT may improve quality of life and prolong life span,but relapse remains a major problem of treatment failure

  10. Adults with Chromosome 18 Abnormalities.

    Science.gov (United States)

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

    2015-08-01

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

  11. Mitogen-Activated Protein Kinase Kinase 3 Regulates Seed Dormancy in Barley.

    Science.gov (United States)

    Nakamura, Shingo; Pourkheirandish, Mohammad; Morishige, Hiromi; Kubo, Yuta; Nakamura, Masako; Ichimura, Kazuya; Seo, Shigemi; Kanamori, Hiroyuki; Wu, Jianzhong; Ando, Tsuyu; Hensel, Goetz; Sameri, Mohammad; Stein, Nils; Sato, Kazuhiro; Matsumoto, Takashi; Yano, Masahiro; Komatsuda, Takao

    2016-03-21

    Seed dormancy has fundamental importance in plant survival and crop production; however, the mechanisms regulating dormancy remain unclear [1-3]. Seed dormancy levels generally decrease during domestication to ensure that crops successfully germinate in the field. However, reduction of seed dormancy can cause devastating losses in cereals like wheat (Triticum aestivum L.) and barley (Hordeum vulgare L.) due to pre-harvest sprouting, the germination of mature seed (grain) on the mother plant when rain occurs before harvest. Understanding the mechanisms of dormancy can facilitate breeding of crop varieties with the appropriate levels of seed dormancy [4-8]. Barley is a model crop [9, 10] and has two major seed dormancy quantitative trait loci (QTLs), SD1 and SD2, on chromosome 5H [11-19]. We detected a QTL designated Qsd2-AK at SD2 as the single major determinant explaining the difference in seed dormancy between the dormant cultivar "Azumamugi" (Az) and the non-dormant cultivar "Kanto Nakate Gold" (KNG). Using map-based cloning, we identified the causal gene for Qsd2-AK as Mitogen-activated Protein Kinase Kinase 3 (MKK3). The dormant Az allele of MKK3 is recessive; the N260T substitution in this allele decreases MKK3 kinase activity and appears to be causal for Qsd2-AK. The N260T substitution occurred in the immediate ancestor allele of the dormant allele, and the established dormant allele became prevalent in barley cultivars grown in East Asia, where the rainy season and harvest season often overlap. Our findings show fine-tuning of seed dormancy during domestication and provide key information for improving pre-harvest sprouting tolerance in barley and wheat. PMID:26948880

  12. Making chromosome abnormalities treatable conditions.

    Science.gov (United States)

    Cody, Jannine DeMars; Hale, Daniel Esten

    2015-09-01

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

  13. Using Chromosomes to Teach Evolution: Chromosomal Rearrangements in Speciation Events.

    Science.gov (United States)

    Offner, Susan

    1994-01-01

    Uses diagrams to aid in discussing how the English map of the human chromosomes, published by Offner in 1993, can be used to illustrate some important questions in evolution, as well as give students a glimpse into some of the mechanisms underlying evolutionary change. (ZWH)

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-08-19

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

  15. 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...

  16. 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...

  17. Chromosome locations of genes encoding human signal transduction adapter proteins, Nck (NCK), Shc (SHC1), and Grb2 (GRB2)

    DEFF Research Database (Denmark)

    Huebner, K; Kastury, K; Druck, T;

    1994-01-01

    Abnormalities due to chromosomal aberration or point mutation in gene products of growth factor receptors or in ras gene products, which lie on the same signaling pathway, can cause disease in animals and humans. Thus, it can be important to determine chromosomal map positions of genes encoding...... "adapter" proteins, which are involved in transducing signals from receptor tyrosine kinases to downstream signal recipients such as ras, because adaptor protein genes could also, logically, serve as targets of mutation, rearrangement, or other aberration in disease. Therefore, DNAs from panels of rodent-human...... hybrids carrying defined complements of human chromosomes were assayed for the presence of the cognate genes for NCK, SHC, and GRB2, three SH2 or SH2/SH3 (Src homology 2 and 3) domain-containing adapter proteins. Additionally, NCK and SHC genes were more narrowly localized by chromosomal in situ...

  18. MET Receptor Tyrosine Kinase

    Science.gov (United States)

    Faoro, Leonardo; Cervantes, Gustavo M.; El-Hashani, Essam; Salgia, Ravi

    2010-01-01

    MET receptor tyrosine kinase (RTK) and its ligand hepatocyte growth factor (HGF) have become important therapeutic target in oncology, especially lung cancer. MET RTK is involved in cancer cell growth/survival, motility/migration, invasion/metastasis, and in angiogenesis. MET can be overexpressed in lung cancer, sometimes mutated, and sometimes amplified. Not only can MET be overexpressed, there are subsets of lung cancer tumors that have HGF overexpression. The mutations of MET can occur in the semaphorin and/or juxtamembrane domain in a majority of times. Amplification of MET can occur de novo in primary/metastatic tumors, as well arise in the context of therapeutic inhibition. There are a number of clinical inhibitors that have been developed against MET/HGF. Small molecule inhibitors such as XL184 and PF02341066 have come to clinical fruition, as well as antibodies against MET (such as MetMAb). These inhibitors will be discussed. PMID:19861919

  19. Mathematical glimpse on the Y chromosome degeneration

    Science.gov (United States)

    Lobo, M. P.

    2006-04-01

    The Y chromosomes are genetically degenerate and do not recombine with their matching partners X. Non-recombination of XY pairs has been pointed out as the key factor for the degeneration of the Y chromosome. The aim here is to show that there is a mathematical asymmetry in sex chromosomes which leads to the degeneration of Y chromosomes even in the absence of XX and XY recombination. A model for sex-chromosome evolution in a stationary regime is proposed. The consequences of their asymmetry are analyzed and lead us to a couple of conclusions. First, Y chromosome degeneration shows up sqrt{2} more often than X chromosome degeneration. Second, if nature prohibits female mortalities from beeing exactly 50%, then Y chromosome degeneration is inevitable.

  20. 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 ...

  1. 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...

  2. 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

  3. 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

  4. 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

  5. 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...

  6. Evolution of sex chromosomes ZW of Schistosoma mansoni inferred from chromosome paint and BAC mapping analyses.

    Science.gov (United States)

    Hirai, Hirohisa; Hirai, Yuriko; LoVerde, Philip T

    2012-12-01

    Chromosomes of schistosome parasites among digenetic flukes have a unique evolution because they exhibit the sex chromosomes ZW, which are not found in the other groups of flukes that are hermaphrodites. We conducted molecular cytogenetic analyses for investigating the sex chromosome evolution using chromosome paint analysis and BAC clones mapping. To carry this out, we developed a technique for making paint probes of genomic DNA from a single scraped chromosome segment using a chromosome microdissection system, and a FISH mapping technique for BAC clones. Paint probes clearly identified each of the 8 pairs of chromosomes by a different fluorochrome color. Combination analysis of chromosome paint analysis with Z/W probes and chromosome mapping with 93 BAC clones revealed that the W chromosome of Schistosoma mansoni has evolved by at least four inversion events and heterochromatinization. Nine of 93 BAC clones hybridized with both the Z and W chromosomes, but the locations were different between Z and W chromosomes. The homologous regions were estimated to have moved from the original Z chromosome to the differentiated W chromosome by three inversions events that occurred before W heterohcromatinization. An inversion that was observed in the heterochromatic region of the W chromosome likely occurred after W heterochromatinization. These inversions and heterochromatinization are hypothesized to be the key factors that promoted the evolution of the W chromosome of S. mansoni. PMID:22831897

  7. Identification of a BET Family Bromodomain/Casein Kinase II/TAF-Containing Complex as a Regulator of Mitotic Condensin Function

    OpenAIRE

    Hyun-Soo Kim; Rituparna Mukhopadhyay; Scott B. Rothbart; Andrea C. Silva; Vincent Vanoosthuyse; Ernest Radovani; Thomas Kislinger; Assen Roguev; Colm J. Ryan; Jiewei Xu; Harlizawati Jahari; Kevin G. Hardwick; Jack F. Greenblatt; Nevan J. Krogan; Jeffrey S. Fillingham

    2014-01-01

    Condensin is a central regulator of mitotic genome structure with mutants showing poorly condensed chromosomes and profound segregation defects. Here, we identify NCT, a complex comprising the Nrc1 BET-family tandem bromodomain protein (SPAC631.02), casein kinase II (CKII), and several TAFs, as a regulator of condensin function. We show that NCT and condensin bind similar genomic regions but only briefly colocalize during the periods of chromosome condensation and decondensation. This pattern...

  8. Chromosome Aberrations by Heavy Ions

    Science.gov (United States)

    Ballarini, Francesca; Ottolenghi, Andrea

    It is well known that mammalian cells exposed to ionizing radiation can show different types of chromosome aberrations (CAs) including dicentrics, translocations, rings, deletions and complex exchanges. Chromosome aberrations are a particularly relevant endpoint in radiobiology, because they play a fundamental role in the pathways leading either to cell death, or to cell conversion to malignancy. In particular, reciprocal translocations involving pairs of specific genes are strongly correlated (and probably also causally-related) with specific tumour types; a typical example is the BCR-ABL translocation for Chronic Myeloid Leukaemia. Furthermore, aberrations can be used for applications in biodosimetry and more generally as biomarkers of exposure and risk, that is the case for cancer patients monitored during Carbon-ion therapy and astronauts exposed to space radiation. Indeed hadron therapy and astronauts' exposure to space radiation represent two of the few scenarios where human beings can be exposed to heavy ions. After a brief introduction on the main general features of chromosome aberrations, in this work we will address key aspects of the current knowledge on chromosome aberration induction, both from an experimental and from a theoretical point of view. More specifically, in vitro data will be summarized and discussed, outlining important issues such as the role of interphase death/mitotic delay and that of complex-exchange scoring. Some available in vivo data on cancer patients and astronauts will be also reported, together with possible interpretation problems. Finally, two of the few available models of chromosome aberration induction by ionizing radiation (including heavy ions) will be described and compared, focusing on the different assumptions adopted by the authors and on how these models can deal with heavy ions.

  9. Purification, crystallization and preliminary X-ray diffraction analysis of the kinase domain of human tousled-like kinase 2

    Energy Technology Data Exchange (ETDEWEB)

    Garrote, Ana M.; Redondo, Pilar [Spanish National Cancer Research Centre (CNIO), Melchor Fernández Almagro 3, 28029 Madrid (Spain); Montoya, Guillermo, E-mail: gmontoya@cnio.es [Spanish National Cancer Research Centre (CNIO), Melchor Fernández Almagro 3, 28029 Madrid (Spain); University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen (Denmark); Muñoz, Inés G., E-mail: gmontoya@cnio.es [Spanish National Cancer Research Centre (CNIO), Melchor Fernández Almagro 3, 28029 Madrid (Spain)

    2014-02-19

    The C-terminal kinase domain of TLK2 (a human tousled-like kinase) has been cloned and overexpressed in Escherichia coli followed by purification to homogeneity. Crystallization experiments in the presence of ATP-γ-S yielded crystals suitable for X-ray diffraction analysis belonging to two different space groups: tetragonal I4{sub 1}22 and cubic P2{sub 1}3. Tousled-like kinases (TLKs) are an evolutionarily conserved family of serine/threonine protein kinases involved in chromatin dynamics, including DNA replication and repair, transcription and chromosome segregation. The two members of the family reported in humans, namely TLK1 and TLK2, localize to the cell nucleus and are capable of forming homo- or hetero-oligomers by themselves. To characterize the role of TLK2, its C-terminal kinase domain was cloned and overexpressed in Escherichia coli followed by purification to homogeneity. Crystallization experiments in the presence of ATP-γ-S yielded crystals suitable for X-ray diffraction analysis belonging to two different space groups: tetragonal I4{sub 1}22 and cubic P2{sub 1}3. The latter produced the best diffracting crystal (3.4 Å resolution using synchrotron radiation), with unit-cell parameters a = b = c = 126.05 Å, α = β = γ = 90°. The asymmetric unit contained one protein molecule, with a Matthews coefficient of 4.59 Å{sup 3} Da{sup −1} and a solvent content of 73.23%.

  10. A case of trisomy of chromosome 15

    OpenAIRE

    Coldwell, S; Fitzgerald, B.; Semmens, J.M.; Ede, R; Bateman, C

    1981-01-01

    We describe a case of trisomy of chromosome 15 in an infant who presented at birth with numerous abnormalities. As far as we are aware this chromosomal abnormality has not been described before. On the basis of this one case there appear to be no features which are specific to this chromosomal abnormality.

  11. The budding yeast Ipl1/Aurora protein kinase regulates mitotic spindle disassembly

    OpenAIRE

    Buvelot, Stéphanie; Tatsutani, Sean Y.; Vermaak, Danielle; Biggins, Sue

    2003-01-01

    Ipl1p is the budding yeast member of the Aurora family of protein kinases, critical regulators of genomic stability that are required for chromosome segregation, the spindle checkpoint, and cytokinesis. Using time-lapse microscopy, we found that Ipl1p also has a function in mitotic spindle disassembly that is separable from its previously identified roles. Ipl1–GFP localizes to kinetochores from G1 to metaphase, transfers to the spindle after metaphase, and accumulates at the spindle midzone ...

  12. Genome-Wide Identification and Expression Analysis of Calcium-dependent Protein Kinase in Tomato

    OpenAIRE

    Hu, Zhangjian; Lv, Xiangzhang; Xia, Xiaojian; Zhou, Jie; Shi, Kai; Yu, Jingquan; Zhou, Yanhong

    2016-01-01

    Calcium-dependent protein kinases (CDPKs) play critical roles in regulating growth, development and stress response in plants. Information about CDPKs in tomato, however, remains obscure although it is one of the most important model crops in the world. In this study, we performed a bioinformatics analysis of the entire tomato genome and identified 29 CDPK genes. These CDPK genes are found to be located in 12 chromosomes, and could be divided into four groups. Analysis of the gene structure a...

  13. Polo-like kinase 1 licenses CENP-A deposition at centromeres

    OpenAIRE

    McKinley, Kara L.; Cheeseman, Iain M.

    2014-01-01

    To ensure the stable transmission of the genome during vertebrate cell division, the mitotic spindle must attach to a single locus on each chromosome, termed the centromere. The fundamental requirement for faithful centromere inheritance is the controlled deposition of the centromere-specifying histone, CENP-A. However, the regulatory mechanisms that ensure the precise control of CENP-A deposition have proved elusive. Here, we identify Polo-like kinase 1 (Plk1) as a centromere-localized regul...

  14. MAP Kinases in Immune Responses

    Institute of Scientific and Technical Information of China (English)

    Yongliang Zhang; Chen Dong

    2005-01-01

    MAP kinases are evolutionarily conserved signaling regulators from budding yeast to mammals and play essential roles in both innate and adaptive immune responses. There are three main families of MAPKs in mammals. Each of them has its own activators, inactivators, substrates and scaffolds, which altogether form a fine signaling network in response to different extracellular or intracellular stimulation. In this review, we summarize recent advances in understanding of the regulation of MAP kinases and the roles of MAP kinases in innate and adaptive immune responses.

  15. 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

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

    OpenAIRE

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

    1994-01-01

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

  17. EGFR kinase-dependent and kinase-independent roles in clear cell renal cell carcinoma.

    Science.gov (United States)

    Cossu-Rocca, Paolo; Muroni, Maria R; Sanges, Francesca; Sotgiu, Giovanni; Asunis, Anna; Tanca, Luciana; Onnis, Daniela; Pira, Giovanna; Manca, Alessandra; Dore, Simone; Uras, Maria G; Ena, Sara; De Miglio, Maria R

    2016-01-01

    Epidermal growth factor receptor (EGFR) is associated with progression of many epithelial malignancies and represents a significant therapeutic target. Although clear cell renal cell carcinoma (CCRCC) has been widely investigated for EGFR molecular alterations, genetic evidences of EGFR gene activating mutations and/or gene amplification have been rarely confirmed in the literature. Therefore, until now EGFR-targeted therapies in clinical trials have been demonstrated unsuccessful. New evidence has been given about the interactions between EGFR and the sodium glucose co-transporter-1 (SGLT1) in maintaining the glucose basal intracellular level to favour cancer cell growth and survival; thus a new functional role may be attributed to EGFR, regardless of its kinase activity. To define the role of EGFR in CCRCC an extensive investigation of genetic changes and functional kinase activities was performed in a series of tumors by analyzing the EGFR mutational status and expression profile, together with the protein expression of downstream signaling pathways members. Furthermore, we investigated the co-expression of EGFR and SGLT1 proteins and their relationships with clinic-pathological features in CCRCC. EGFR protein expression was identified in 98.4% of CCRCC. Furthermore, it was described for the first time that SGLT1 is overexpressed in CCRCC (80.9%), and that co-expression with EGFR is appreciable in 79.4% of the tumours. Moreover, the activation of downstream EGFR pathways was found in about 79.4% of SGLT1-positive CCRCCs. The mutational status analysis of EGFR failed to demonstrate mutations on exons 18 to 24 and the presence of EGFR-variantIII (EGFRvIII) in all CCRCCs analyzed. FISH analysis revealed absence of EGFR amplification, and high polysomy of chromosome 7. Finally, the EGFR gene expression profile showed gene overexpression in 38.2% of CCRCCs. Our study contributes to define the complexity of EGFR role in CCRCC, identifying its bivalent kinase

  18. Temporal genomic evolution of bird sex chromosomes

    DEFF Research Database (Denmark)

    Wang, Zongji; Zhang, Jilin; Yang, Wei;

    2014-01-01

    driving forces of Z chromosome evolution, we analyze here 45 newly available bird genomes and four species' transcriptomes, over their course of recombination loss between the sex chromosomes. RESULTS: We show Z chromosomes in general have a significantly higher substitution rate in introns and synonymous...... evolved very recently. CONCLUSIONS: In conclusion, we uncover that the sequence and expression patterns of Z chromosome genes covary with their ages of becoming Z-linked. In contrast to the mammalian X chromosomes, such patterns are mainly driven by mutational bias and genetic drift in birds, due...... to the opposite sex-biased inheritance of Z vs. X....

  19. Holoprosencephaly due to numeric chromosome abnormalities.

    Science.gov (United States)

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

    2010-02-15

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

  20. 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.

  1. Isolation of chloroplastic phosphoglycerate kinase

    Energy Technology Data Exchange (ETDEWEB)

    Macioszek, J.; Anderson, L.E. (Univ. of Illinois, Chicago (USA)); Anderson, J.B. (Pennsylvania State Univ., University Park (USA))

    1990-09-01

    We report here a method for the isolation of high specific activity phosphoglycerate kinase (EC 2.7.2.3) from chloroplasts. The enzyme has been purified over 200-fold from pea (Pisum sativum L.) stromal extracts to apparent homogeneity with 23% recovery. Negative cooperativity is observed with the two enzyme phosphoglycerate kinase/glyceraldehyde-3-P dehydrogenase (EC 1.2.1.13) couple restored from the purified enzymes when NADPH is the reducing pyridine nucleotide, consistent with earlier results obtained with crude chloroplastic extracts. Michaelis Menten kinetics are observed when 3-phosphoglycerate is held constant and phosphoglycerate kinase is varied, which suggests that phosphoglycerate kinase-bound 1,3-bisphosphoglycerate may be the preferred substrate for glyceraldehyde-3-P dehydrogenase in the chloroplast.

  2. Protein Crystals of Raf Kinase

    Science.gov (United States)

    1995-01-01

    This image shows crystals of the protein raf kinase grown on Earth (photo a) and on USML-2 (photo b). The space-grown crystals are an order of magnitude larger. Principal Investigator: Dan Carter of New Century Pharmaceuticals

  3. Transient Microgeographic Clines during B Chromosome Invasion.

    Science.gov (United States)

    Camacho, Juan Pedro M; Shaw, Michael W; Cabrero, Josefa; Bakkali, Mohammed; Ruíz-Estévez, Mercedes; Ruíz-Ruano, Francisco J; Martín-Blázquez, Rubén; López-León, María Dolores

    2015-11-01

    The near-neutral model of B chromosome evolution predicts that the invasion of a new population should last some tens of generations, but the details on how it proceeds in real populations are mostly unknown. Trying to fill this gap, we analyze here a natural population of the grasshopper Eyprepocnemis plorans at three time points during the last 35 years. Our results show that B chromosome frequency increased significantly during this period and that a cline observed in 1992 had disappeared in 2012 once B chromosome frequency reached an upper limit at all sites sampled. This indicates that, during B chromosome invasion, transient clines for B chromosome frequency are formed at the invasion front on a microgeographic scale. Computer simulation experiments showed that the pattern of change observed for genotypic frequencies is consistent with the existence of B chromosome drive through females and selection against individuals with a high number of B chromosomes. PMID:26655780

  4. 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

  5. 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.

  6. [The evolution of human Y chromosome].

    Science.gov (United States)

    Yang, Xianrong; Wang, Meiqin; Li, Shaohua

    2014-09-01

    The human Y chromosome is always intriguing for researchers, because of its role in gender determination and its unusual evolutionary history. The Y chromosome evolves from an autosome, and its evolution has been characterized by massive gene decay. The lack of recombination and protein-coding genes and high content of repetitive sequences have hindered the progress in our understanding of the Y chromosome biology. Recently, with the advances in comparative genomics and sequencing technology, the research on Y chromosome has become a hotspot, with an intensified debate about Y-chromosome final destination resulting from degeneration. This review focuses on the structure, inheritance characteristics, gene content, and the origin and evolution of Y chromosome. We also discuss the long-term destiny of Y chromosome. PMID:25252301

  7. 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 this...... and reliable 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...... on the P1 par system. Using 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...

  8. 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...

  9. Sequence-specific targeting of dosage compensation in Drosophila favors an active chromatin context.

    Directory of Open Access Journals (Sweden)

    Artyom A Alekseyenko

    Full Text Available The Drosophila MSL complex mediates dosage compensation by increasing transcription of the single X chromosome in males approximately two-fold. This is accomplished through recognition of the X chromosome and subsequent acetylation of histone H4K16 on X-linked genes. Initial binding to the X is thought to occur at "entry sites" that contain a consensus sequence motif ("MSL recognition element" or MRE. However, this motif is only ∼2 fold enriched on X, and only a fraction of the motifs on X are initially targeted. Here we ask whether chromatin context could distinguish between utilized and non-utilized copies of the motif, by comparing their relative enrichment for histone modifications and chromosomal proteins mapped in the modENCODE project. Through a comparative analysis of the chromatin features in male S2 cells (which contain MSL complex and female Kc cells (which lack the complex, we find that the presence of active chromatin modifications, together with an elevated local GC content in the surrounding sequences, has strong predictive value for functional MSL entry sites, independent of MSL binding. We tested these sites for function in Kc cells by RNAi knockdown of Sxl, resulting in induction of MSL complex. We show that ectopic MSL expression in Kc cells leads to H4K16 acetylation around these sites and a relative increase in X chromosome transcription. Collectively, our results support a model in which a pre-existing active chromatin environment, coincident with H3K36me3, contributes to MSL entry site selection. The consequences of MSL targeting of the male X chromosome include increase in nucleosome lability, enrichment for H4K16 acetylation and JIL-1 kinase, and depletion of linker histone H1 on active X-linked genes. Our analysis can serve as a model for identifying chromatin and local sequence features that may contribute to selection of functional protein binding sites in the genome.

  10. Purification, crystallization and preliminary X-ray diffraction analysis of the kinase domain of human tousled-like kinase 2.

    Science.gov (United States)

    Garrote, Ana M; Redondo, Pilar; Montoya, Guillermo; Muñoz, Inés G

    2014-03-01

    Tousled-like kinases (TLKs) are an evolutionarily conserved family of serine/threonine protein kinases involved in chromatin dynamics, including DNA replication and repair, transcription and chromosome segregation. The two members of the family reported in humans, namely TLK1 and TLK2, localize to the cell nucleus and are capable of forming homo- or hetero-oligomers by themselves. To characterize the role of TLK2, its C-terminal kinase domain was cloned and overexpressed in Escherichia coli followed by purification to homogeneity. Crystallization experiments in the presence of ATP-γ-S yielded crystals suitable for X-ray diffraction analysis belonging to two different space groups: tetragonal I4122 and cubic P213. The latter produced the best diffracting crystal (3.4 Å resolution using synchrotron radiation), with unit-cell parameters a = b = c = 126.05 Å, α = β = γ = 90°. The asymmetric unit contained one protein molecule, with a Matthews coefficient of 4.59 Å(3) Da(-1) and a solvent content of 73.23%. PMID:24598926

  11. International workshop of chromosome 19

    Energy Technology Data Exchange (ETDEWEB)

    Pericak-Vance, M.A. (Duke Univ. Medical Center, Durham, NC (United States). Div. of Neurology); Carrano, A.J. (Lawrence Livermore National Lab., CA (United States))

    1991-09-16

    This document summarizes the workshop on physical and genetic mapping of chromosome 19. The first session discussed the major disease loci found on the chromosome. The second session concentrated on reference families, markers and linkage maps. The third session concentrated on radiation hybrid mapping, somatic cell hybrid panels, macro restriction maps and YACs, followed by cDNA and long range physical maps. The fourth session concentrated on compiling consensus genetic and physical maps as well as discussing regions of conflict. The final session dealt with the LLNL cosmid contig database and comparative mapping of homologous regions of the human and mouse genomes, and ended with a discussion of resource sharing. 18 refs., 2 figs. (MHB)

  12. Baseline chromosome aberrations in children

    Czech Academy of Sciences Publication Activity Database

    Merlo, D.F.; Ceppi, M.; Stagi, E.; Bocchini, V.; Šrám, Radim; Rössner st., Pavel

    2007-01-01

    Roč. 172, - (2007), s. 60-67. ISSN 0378-4274 Grant ostatní: EU(EU) 2002-02198; EU(EU) 2005-016320 Institutional research plan: CEZ:AV0Z50390512 Source of funding: R - rámcový projekt EK ; R - rámcový projekt EK Keywords : chromosome aberrations * children * molecular epidemiology Subject RIV: DN - Health Impact of the Environment Quality Impact factor: 2.826, year: 2007

  13. Clonality - X Chromosome Inactivation Assay

    OpenAIRE

    sprotocols

    2014-01-01

    Author: Molecular Profiling Initiative, NCI This method was successful in our lab using prostate tissue and for our specific objectives. Investigators must be aware that they will need to tailor the following protocol for their own research objectives and tissue under study. Investigators can utilize X chromosome inactivation (methylation) to determine the clonality status of a tumor or premalignant lesion in females. The technique is based on a methylation-sensitive restriction enzym...

  14. Hobo transposons causing chromosomal breakpoints.

    OpenAIRE

    Ladevèze, V; Aulard, S.; Chaminade, N; Périquet, G; Lemeunier, F

    1998-01-01

    Several laboratory surveys have shown that transposable elements (TEs) can cause chromosomal breaks and lead to inversions, as in dysgenic crosses involving P-elements. However, it is not presently clear what causes inversions in natural populations of Drosophila. The only direct molecular studies must be taken as evidence against the involvement of mobile elements. Here, in Drosophila lines transformed with the hobo transposable element, and followed for 100 generations, we show the appearan...

  15. 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....

  16. 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.

  17. 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

  18. Comparative analysis of sex chromosomes in Leporinus species (Teleostei, Characiformes) using chromosome painting

    Science.gov (United States)

    2013-01-01

    Background The Leporinus genus, belonging to the Anostomidae family, is an interesting model for studies of sex chromosome evolution in fish, particularly because of the presence of heteromorphic sex chromosomes only in some species of the genus. In this study we used W chromosome-derived probes in a series of cross species chromosome painting experiments to try to understand events of sex chromosome evolution in this family. Results W chromosome painting probes from Leporinus elongatus, L. macrocephalus and L. obtusidens were hybridized to each others chromosomes. The results showed signals along their W chromosomes and the use of L. elongatus W probe against L. macrocephalus and L. obtusidens also showed signals over the Z chromosome. No signals were observed when the later aforementioned probe was used in hybridization procedures against other four Anostomidae species without sex chromosomes. Conclusions Our results demonstrate a common origin of sex chromosomes in L. elongatus, L. macrocephalus and L. obtusidens but suggest that the L. elongatus chromosome system is at a different evolutionary stage. The absence of signals in the species without differentiated sex chromosomes does not exclude the possibility of cryptic sex chromosomes, but they must contain other Leporinus W sequences than those described here. PMID:23822802

  19. 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

  20. 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.

  1. 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.

  2. 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

  3. BAC-FISH assays delineate complex chromosomal rearrangements in a case of post-Chernobyl childhood thyroid cancer.

    Directory of Open Access Journals (Sweden)

    Horst F Zitzelsberger

    2009-12-01

    Full Text Available Structural chromosome aberrations are known hallmarks of many solid tumors. In the papillary form of thyroid cancer (PTC, for example, activation of the receptor tyrosine kinase (RTK genes, RET and neurotrophic tyrosine kinase receptor type I (NTRK1 by intra- and interchromosomal rearrangements has been suggested as a cause of the disease. However, many phenotypically similar tumors do not carry an activated RET or NTRK-1 gene or express abnormal ret or NTRK-1 transcripts. Thus, we hypothesize that other cellular RTK-type genes are aberrantly expressed in these tumors. Using fluorescence in situ hybridization-based methods, we are studying karyotype changes in a relatively rare subgroup of PTCs, i.e., tumors that arose in children following the 1986 nuclear accident in Chernobyl, Ukraine. Here, we report our technical developments and progress in deciphering complex chromosome aberrations in case S48TK, an aggressively growing PTC cell line, which shows an unusual high number of unbalanced translocations.

  4. BAC-FISH assays delineate complex chromosomal rearrangements in a case of post-Chernobyl childhood thyroid cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kwan, Johnson; Baumgartner, Adolf; Lu, Chun-Mei; Wang, Mei; Weier, Jingly F.; Zitzelsberger, Horst F.; Weier, Heinz-Ulrich G.

    2009-03-09

    Structural chromosome aberrations are known hallmarks of many solid tumors. In the papillary form of thyroid cancer (PTC), for example, activation of the receptor tyrosine kinase (RTK) genes, RET and neurotrophic tyrosine kinase receptor type I (NTRK1) by intra- and interchromosomal rearrangements has been suggested as a cause of the disease. However, many phenotypically similar tumors do not carry an activated RET or NTRK-1 gene or express abnormal ret or NTRK-1 transcripts. Thus, we hypothesize that other cellular RTK-type genes are aberrantly expressed in these tumors. Using fluorescence in situ hybridization-based methods, we are studying karyotype changes in a relatively rare subgroup of PTCs, i.e., tumors that arose in children following the 1986 nuclear accident in Chernobyl, Ukraine. Here, we report our technical developments and progress in deciphering complex chromosome aberrations in case S48TK, an aggressively growing PTC cell line, which shows an unusual high number of unbalanced translocations.

  5. BAC-FISH assays delineate complex chromosomal rearrangements in a case of post-Chernobyl childhood thyroid cancer

    International Nuclear Information System (INIS)

    Structural chromosome aberrations are known hallmarks of many solid tumors. In the papillary form of thyroid cancer (PTC), for example, activation of the receptor tyrosine kinase (RTK) genes, RET and neurotrophic tyrosine kinase receptor type I (NTRK1) by intra- and interchromosomal rearrangements has been suggested as a cause of the disease. However, many phenotypically similar tumors do not carry an activated RET or NTRK-1 gene or express abnormal ret or NTRK-1 transcripts. Thus, we hypothesize that other cellular RTK-type genes are aberrantly expressed in these tumors. Using fluorescence in situ hybridization-based methods, we are studying karyotype changes in a relatively rare subgroup of PTCs, i.e., tumors that arose in children following the 1986 nuclear accident in Chernobyl, Ukraine. Here, we report our technical developments and progress in deciphering complex chromosome aberrations in case S48TK, an aggressively growing PTC cell line, which shows an unusual high number of unbalanced translocations. (authors)

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

    Science.gov (United States)

    Pandey, Ravi S; Azad, Rajeev K

    2016-03-01

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

  7. Chromosome engineering: power tools for plant genetics.

    Science.gov (United States)

    Chan, Simon W L

    2010-12-01

    The term "chromosome engineering" describes technologies in which chromosomes are manipulated to change their mode of genetic inheritance. This review examines recent innovations in chromosome engineering that promise to greatly increase the efficiency of plant breeding. Haploid Arabidopsis thaliana have been produced by altering the kinetochore protein CENH3, yielding instant homozygous lines. Haploid production will facilitate reverse breeding, a method that downregulates recombination to ensure progeny contain intact parental chromosomes. Another chromosome engineering success is the conversion of meiosis into mitosis, which produces diploid gametes that are clones of the parent plant. This is a key step in apomixis (asexual reproduction through seeds) and could help to preserve hybrid vigor in the future. New homologous recombination methods in plants will potentiate many chromosome engineering applications. PMID:20933291

  8. 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)

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

    OpenAIRE

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

    2015-01-01

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

  10. Msc1 Acts Through Histone H2A.Z to Promote Chromosome Stability in Schizosaccharomyces pombe

    OpenAIRE

    Ahmed, Shakil; Dul, Barbara; Qiu, Xinxing; Walworth, Nancy C.

    2007-01-01

    As a central component of the DNA damage checkpoint pathway, the conserved protein kinase Chk1 mediates cell cycle progression when DNA damage is generated. Msc1 was identified as a multicopy suppressor capable of facilitating survival in response to DNA damage of cells mutant for chk1. We demonstrate that loss of msc1 function results in an increased rate of chromosome loss and that an msc1 null allele exhibits genetic interactions with mutants in key kinetochore components. Multicopy expres...

  11. 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...

  12. 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...

  13. Identification of bacterial cells by chromosomal painting.

    OpenAIRE

    Lanoil, B. D.; Giovannoni, S J

    1997-01-01

    Chromosomal painting is a technique for the microscopic localization of genetic material. It has been applied at the subcellular level to identify regions of eukaryotic chromosomes. Here we describe the development of bacterial chromosomal painting (BCP), a related technology for the identification of bacterial cells. Purified genomic DNAs from six bacterial strains were labeled by nick translation with the fluorochrome Fluor-X, Cy3, or Cy5. The average size of the labeled fragments was ca. 5...

  14. Holoprosencephaly due to Numeric Chromosome Abnormalities

    OpenAIRE

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

    2010-01-01

    Holoprosencephaly (HPE) is the most common malformation of the human forebrain. When a clinician identifies a patient with HPE, a routine chromosome analysis is often the first genetic test sent for laboratory analysis in order to assess for a structural or numerical chromosome anomaly. An abnormality of chromosome number is overall the most frequently identified etiology in a patient with HPE. These abnormalities include trisomy 13, trisomy 18, and triploidy, though several others have been ...

  15. 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...

  16. 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...

  17. Advances in plant chromosome genomics

    Czech Academy of Sciences Publication Activity Database

    Doležel, Jaroslav; Vrána, Jan; Cápal, Petr; Kubaláková, Marie; Burešová, Veronika; Šimková, Hana

    2014-01-01

    Roč. 32, č. 1 (2014), s. 122-136. ISSN 0734-9750 R&D Projects: GA ČR GAP501/10/1740; GA ČR GAP501/10/1778; GA ČR GBP501/12/G090; GA MŠk(CZ) LO1204 Grant ostatní: GA MŠk(CZ) ED0007/01/01 Institutional support: RVO:61389030 Keywords : BAC library * Chromosome sorting * Cytogenetics Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 9.015, year: 2014

  18. 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...

  19. The emerging pathogenic and therapeutic importance of the anaplastic lymphoma kinase gene.

    LENUS (Irish Health Repository)

    Kelleher, Fergal C

    2012-02-01

    The anaplastic lymphoma kinase gene (ALK) is a gene on chromosome 2p23 that has expression restricted to the brain, testis and small intestine but is not expressed in normal lymphoid tissue. It has similarity to the insulin receptor subfamily of kinases and is emerging as having increased pathologic and potential therapeutic importance in malignant disease. This gene was originally established as being implicated in the pathogenesis of rare diseases including inflammatory myofibroblastic tumour (IMT) and ALK-positive anaplastic large cell lymphoma, which is a subtype of non-Hodgkin\\'s lymphoma. Recently the number of diseases in which ALK is implicated in their pathogenesis has increased. In 2007, an inversion of chromosome 2 involving ALK and a fusion partner gene in a subset of non-small cell lung cancer was discovered. In 2008, publications emerged implicating ALK in familial and sporadic cases of neuroblastoma, a childhood cancer of the sympatho-adrenal system. Chromosomal abnormalities involving ALK are translocations, amplifications or mutations. Chromosomal translocations are the longest recognised ALK genetic abnormality. When translocations occur a fusion gene is created between ALK and a gene partner. This has been described in ALK-positive anaplastic large cell lymphoma in which ALK is fused to NPM (nucleolar protein gene) and in non-small cell lung cancer where ALK is fused to EML4 (Echinoderm microtubule-associated protein 4). The most frequently described partner genes in inflammatory myofibroblastic tumour are tropomyosin 3\\/4 (TMP3\\/4), however in IMTs a diversity of ALK fusion partners have been found, with the ability to homodimerise a common characteristic. Point mutations and amplification of the ALK gene occur in the childhood cancer neuroblastoma. Therapeutic targeting of ALK fusion genes using tyrosine kinase inhibition, vaccination using an ALK specific antigen and treatment using viral vectors for RNAi are emerging potential therapeutic

  20. Chromosome banding in Amphibia. XXIV. The B chromosomes of Gastrotheca espeletia (Anura, Hylidae).

    Science.gov (United States)

    Schmid, M; Ziegler, C G; Steinlein, C; Nanda, I; Haaf, T

    2002-01-01

    The mitotic chromosomes of an Ecuadorian population of the marsupial frog Gastrotheca espeletia were analyzed by means of banding techniques and fluorescence in situ hybridization. This species is characterized by unusual supernumerary (B) chromosomes. The maximum number of B chromosomes is 9 and they occur in three different morphological types. Banding analyses show that the B chromosomes are completely heterochromatic, consist of AT base pair-rich repeated DNA sequences, replicate their DNA in very late S-phase of the cell cycle, and are probably derived from a centromeric or paracentromeric region of a standard (A) chromosome. Exceptionally, the B chromosomes carry 18S + 28S ribosomal RNA genes and the conserved vertebrate telomeric DNA sequence appears to be underrepresented. Flow cytometric measurements of the nuclear DNA content differentiate between individuals with different numbers of B chromosomes. Significantly more B chromosomes are present in female than in male animals. PMID:12438715

  1. Giemsa C-banding of Barley Chromosomes. IV. Chromosomal Constitution of Autotetraploid Barley

    DEFF Research Database (Denmark)

    Linde-Laursen, Ib

    1984-01-01

    homologues of each of the chromosomes. The aneuploid C2--seedlings were fairly equally distributed on hypo-and hyperploids, and on the seven chromosome groups. This suggests that a particular chromosome is lost or gained at random in gametes and embryos. The 11 C3--seedlings comprised seven true euploids......The progeny of an autotetraploid barley plant (C1) consisted of 45 tetraploids and 33 aneuploids. Giemsa C-banding was used to identify each of the chromosomes in 20 euploid and 31 aneuploid C2--seedlings, and in 11 C3--offspring of aneuploid C2--plants. The euploid C2--seedlings all had four......, one seedling with 2n=28 having an extra chromosome 6 and missing one chromosome 3, and three seedlings with 2n=29. The chromosomal composition of aneuploid C3--seedlings did not reflect that of their aneuploid C2--parents with respect to missing or extra chromosomes. Two hypohexaploid C2--seedlings...

  2. BUBR1 recruits PP2A via the B56 family of targeting subunits to promote chromosome congression

    Directory of Open Access Journals (Sweden)

    Peng Xu

    2013-03-01

    BUBR1 is a mitotic phosphoprotein essential for the maintenance of chromosome stability by promoting chromosome congression and proper kinetochore–microtubule (K-fiber attachment, but the underlying mechanism(s has remained elusive. Here we identify BUBR1 as a binding partner of the B56 family of Protein Phosphatase 2A regulatory subunits. The interaction between BUBR1 and the B56 family is required for chromosome congression, since point mutations in BUBR1 that block B56 binding abolish chromosome congression. The BUBR1:B56-PP2A complex opposes Aurora B kinase activity, since loss of the complex can be reverted by inhibiting Aurora B. Importantly, we show that the failure of BUBR1 to recruit B56-PP2A also contributes to the chromosome congression defects found in cells derived from patients with the Mosaic Variegated Aneuploidy (MVA syndrome. Together, we propose that B56-PP2A is a key mediator of BUBR1's role in chromosome congression and functions by antagonizing Aurora B activity at the kinetochore for establishing stable kinetochore–microtubule attachment at the metaphase plate.

  3. 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...

  4. 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.

  5. 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)

  6. 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

  7. Chromosomal aberrations in ore miners of Slovakia

    International Nuclear Information System (INIS)

    A pilot study was performed in which the incidence of chromosomal aberrations in lymphocytes of miners in ore mines located in Central Slovakia was monitored and related to lifetime underground radon exposure and to lifetime smoking. The conclusions drawn from the results of the study were as follows: the counts of chromosomal aberrations in lymphocytes of miners were significantly higher than in an age matched control group of white-collar staff; the higher counts of chromosomal aberrations could be ascribed to underground exposure of miners and to smoking; a dependence of chromosomal aberration counts on the exposure to radon could not be assessed. (A.K.)

  8. Quantitative mass spectrometry analysis reveals similar substrate consensus motif for human Mps1 kinase and Plk1.

    Directory of Open Access Journals (Sweden)

    Zhen Dou

    Full Text Available BACKGROUND: Members of the Mps1 kinase family play an essential and evolutionarily conserved role in the spindle assembly checkpoint (SAC, a surveillance mechanism that ensures accurate chromosome segregation during mitosis. Human Mps1 (hMps1 is highly phosphorylated during mitosis and many phosphorylation sites have been identified. However, the upstream kinases responsible for these phosphorylations are not presently known. METHODOLOGY/PRINCIPAL FINDINGS: Here, we identify 29 in vivo phosphorylation sites in hMps1. While in vivo analyses indicate that Aurora B and hMps1 activity are required for mitotic hyper-phosphorylation of hMps1, in vitro kinase assays show that Cdk1, MAPK, Plk1 and hMps1 itself can directly phosphorylate hMps1. Although Aurora B poorly phosphorylates hMps1 in vitro, it positively regulates the localization of Mps1 to kinetochores in vivo. Most importantly, quantitative mass spectrometry analysis demonstrates that at least 12 sites within hMps1 can be attributed to autophosphorylation. Remarkably, these hMps1 autophosphorylation sites closely resemble the consensus motif of Plk1, demonstrating that these two mitotic kinases share a similar substrate consensus. CONCLUSIONS/SIGNIFICANCE: hMps1 kinase is regulated by Aurora B kinase and its autophosphorylation. Analysis on hMps1 autophosphorylation sites demonstrates that hMps1 has a substrate preference similar to Plk1 kinase.

  9. 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.

  10. Increased chromosome radiosensitivity during pregnancy

    International Nuclear Information System (INIS)

    It was necessary to consider the risks of exposure of pregnant women, not only in relation to the child, but also in relation to their own hypersensitivity. We have demonstrated that pregnancy increases radiosensitivity of chromosome in the mouse at the end of gestation. This is of importance since it may have implications on radioprotection of pregnant women and give experimental guidelines to the problems of hypersensitivity to drugs and cancer aggravation during pregnancy. Blood obtained from women at various times of pregnancy was exposed to ionizing radiations. By comparison to non-pregnant women, an increase in chromosome breakage was observed in metaphases from lymphocytes, after short-term culture in the presence of the serum of the same donor. Immediately after delivery, this increase in radiosensitivity disappeared. In a prospective study, serial analyses showed a very strong correlation between the amount of pregnancy hormones, progesterone in particular, and the increase in radiosensitivity. Pregnant women may have an increased sensitivity to ionizing radiation during the second half of their pregnancy. This study provides the first evidence in human that radiosensitivity may vary in relation to physiological conditions

  11. Retrospective dosimetry by chromosomal analysis

    International Nuclear Information System (INIS)

    The joint EU/CIS project ECP-6, was set up to examine whether cytogenetic dosimetry is possible for persons irradiated years previously at Chernobyl. The paper describes the possibility of achieving this by the examination of blood lymphocytes for unstable and stable chromosome aberrations; dicentrics and translocations. Emphasis was placed on the relatively new fluorescence in situ hybridization (FISH) method for rapid screening for stable translocations. In a collaborative experiment in vitro dose response calibration curves for dicentrics and FISH were produced with gamma radiation over the range 0-1.0 Gy. A pilot study of about 60 liquidators with registered doses ranging from 0-300 mSv was undertaken to determine whether the chromosomal methods may verify the recorded doses. It was concluded that the dicentric is no longer valid as a measured endpoint. Translocations may be used to verify early dosimetry carried out on highly irradiated persons. For the vast majority of lesser exposed subjects FISH is impractical as an individual dosimeter; it may have some value for comparing groups of subjects

  12. 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

  13. Chromosomal replicons of higher plants

    International Nuclear Information System (INIS)

    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

  14. The X chromosome of monotremes shares a highly conserved region with the eutherian and marsupial X chromosomes despite the absence of X chromosome inactivation

    Energy Technology Data Exchange (ETDEWEB)

    Watson, J.M.; Spencer, J.A.; Graves, J.A.M. (La Trobe Univ., Bundoora, Victoria (Australia)); Riggs, A.D. (Beckman Inst., Duarte, CA (USA))

    1990-09-01

    Eight genes, located on the long arm of the human X chromosome and present on the marsupial X chromosome, were mapped by in situ hybridization to the chromosomes of the platypus Ornithorhynchus anatinus, one of the three species of monotreme mammals. All were located on the X chromosome. The authors conclude that the long arm of the human X chromosome represents a highly conserved region that formed part of the X chromosome in a mammalian ancestor at least 150 million years ago. Since three of these genes are located on the long arm of the platypus X chromosome, which is G-band homologous to the Y chromosome and apparently exempt from X chromosome inactivation, the conservation of this region has evidently not depended on isolation by X-Y chromosome differentiation and X chromosome inactivation.

  15. ATM promotes the obligate XY crossover and both crossover control and chromosome axis integrity on autosomes.

    Directory of Open Access Journals (Sweden)

    Marco Barchi

    2008-05-01

    Full Text Available During meiosis in most sexually reproducing organisms, recombination forms crossovers between homologous maternal and paternal chromosomes and thereby promotes proper chromosome segregation at the first meiotic division. The number and distribution of crossovers are tightly controlled, but the factors that contribute to this control are poorly understood in most organisms, including mammals. Here we provide evidence that the ATM kinase or protein is essential for proper crossover formation in mouse spermatocytes. ATM deficiency causes multiple phenotypes in humans and mice, including gonadal atrophy. Mouse Atm-/- spermatocytes undergo apoptosis at mid-prophase of meiosis I, but Atm(-/- meiotic phenotypes are partially rescued by Spo11 heterozygosity, such that ATM-deficient spermatocytes progress to meiotic metaphase I. Strikingly, Spo11+/-Atm-/- spermatocytes are defective in forming the obligate crossover on the sex chromosomes, even though the XY pair is usually incorporated in a sex body and is transcriptionally inactivated as in normal spermatocytes. The XY crossover defect correlates with the appearance of lagging chromosomes at metaphase I, which may trigger the extensive metaphase apoptosis that is observed in these cells. In addition, control of the number and distribution of crossovers on autosomes appears to be defective in the absence of ATM because there is an increase in the total number of MLH1 foci, which mark the sites of eventual crossover formation, and because interference between MLH1 foci is perturbed. The axes of autosomes exhibit structural defects that correlate with the positions of ongoing recombination. Together, these findings indicate that ATM plays a role in both crossover control and chromosome axis integrity and further suggests that ATM is important for coordinating these features of meiotic chromosome dynamics.

  16. Structure and chromosomal localization of the human PD-1 gene (PDCD1)

    Energy Technology Data Exchange (ETDEWEB)

    Shinohara, T.; Ishida, Y.; Kawaichi, M. [Kyoto Prefectural Medical School, Sakyo-ku (Japan)] [and others

    1994-10-01

    A cDNA encoding mouse PD-1, a member of the immunoglobulin superfamily, was previously isolated from apoptosis-induced cells by subtractive hybridization. To determine the structure and chromosomal location of the human PD-1 gene, we screened a human T cell cDNA library by mouse PD-1 probe and isolated a cDNA coding for the human PD-1 protein. The deduced amino acid sequence of human PD-1 was 60% identical to the mouse counterpart, and a putative tyrosine kinase-association motif was well conserved. The human PD-1 gene was mapped to 2q37.3 by chromosomal in situ hybridization. 7 refs., 3 figs.

  17. Aurora B regulates formin mDia3 in achieving metaphase chromosome alignment.

    Science.gov (United States)

    Cheng, Lina; Zhang, Jiayin; Ahmad, Sana; Rozier, Lorene; Yu, Haiqian; Deng, Haiteng; Mao, Yinghui

    2011-03-15

    Proper bipolar attachment of sister kinetochores to the mitotic spindle is critical for accurate chromosome segregation in mitosis. Here we show an essential role of the formin mDia3 in achieving metaphase chromosome alignment. This function is independent of mDia3 actin nucleation activity, but is attributable to EB1-binding by mDia3. Furthermore, the microtubule binding FH2 domain of mDia3 is phosphorylated by Aurora B kinase in vitro, and cells expressing the nonphosphorylatable mDia3 mutant cannot position chromosomes at the metaphase plate. Purified recombinant mDia3 phosphorylated by Aurora B exhibits reduced ability to bind microtubules and stabilize microtubules against cold-induced disassembly in vitro. Cells expressing the phosphomimetic mDia3 mutant do not form stable kinetochore microtubule fibers; despite they are able to congress chromosomes to the metaphase plate. These findings reveal a key role for mDia3 and its regulation by Aurora B phosphorylation in achieving proper stable kinetochore microtubule attachment. PMID:21397845

  18. Chromosomal painting and ZW sex chromosomes differentiation in Characidium (Characiformes, Crenuchidae

    Directory of Open Access Journals (Sweden)

    Artoni Roberto F

    2011-07-01

    Full Text Available Abstract Background The Characidium (a Neotropical fish group have a conserved diploid number (2n = 50, but show remarkable differences among species and populations in relation to sex chromosome systems and location of nucleolus organizer regions (NOR. In this study, we isolated a W-specific probe for the Characidium and characterized six Characidium species/populations using cytogenetic procedures. We analyzed the origin and differentiation of sex and NOR-bearing chromosomes by chromosome painting in populations of Characidium to reveal their evolution, phylogeny, and biogeography. Results A W-specific probe for efficient chromosome painting was isolated by microdissection and degenerate oligonucleotide primed-polymerase chain reaction (DOP-PCR amplification of W chromosomes from C. gomesi. The W probe generated weak signals dispersed on the proto sex chromosomes in C. zebra, dispersed signals in both W and Z chromosomes in C. lauroi and, in C. gomesi populations revealed a proximal site on the long arms of the Z chromosome and the entire W chromosome. All populations showed small terminal W probe sites in some autosomes. The 18S rDNA revealed distinctive patterns for each analyzed species/population with regard to proto sex chromosome, sex chromosome pair, and autosome location. Conclusions The results from dual-color fluorescence in situ hybridization (dual-color FISH using W and 18S rDNA probes allowed us to infer the putative evolutionary pathways for the differentiation of sex chromosomes and NORs, from structural rearrangements in a sex proto-chromosome, followed by gene erosion and heterochromatin amplification, morphological differentiation of the sex chromosomal pair, and NOR transposition, giving rise to the distinctive patterns observed among species/populations of Characidium. Biogeographic isolation and differentiation of sex chromosomes seem to have played a major role in the speciation process in this group of fish.

  19. Chromosomal painting and ZW sex chromosomes differentiation in Characidium (Characiformes, Crenuchidae)

    Science.gov (United States)

    2011-01-01

    Background The Characidium (a Neotropical fish group) have a conserved diploid number (2n = 50), but show remarkable differences among species and populations in relation to sex chromosome systems and location of nucleolus organizer regions (NOR). In this study, we isolated a W-specific probe for the Characidium and characterized six Characidium species/populations using cytogenetic procedures. We analyzed the origin and differentiation of sex and NOR-bearing chromosomes by chromosome painting in populations of Characidium to reveal their evolution, phylogeny, and biogeography. Results A W-specific probe for efficient chromosome painting was isolated by microdissection and degenerate oligonucleotide primed-polymerase chain reaction (DOP-PCR) amplification of W chromosomes from C. gomesi. The W probe generated weak signals dispersed on the proto sex chromosomes in C. zebra, dispersed signals in both W and Z chromosomes in C. lauroi and, in C. gomesi populations revealed a proximal site on the long arms of the Z chromosome and the entire W chromosome. All populations showed small terminal W probe sites in some autosomes. The 18S rDNA revealed distinctive patterns for each analyzed species/population with regard to proto sex chromosome, sex chromosome pair, and autosome location. Conclusions The results from dual-color fluorescence in situ hybridization (dual-color FISH) using W and 18S rDNA probes allowed us to infer the putative evolutionary pathways for the differentiation of sex chromosomes and NORs, from structural rearrangements in a sex proto-chromosome, followed by gene erosion and heterochromatin amplification, morphological differentiation of the sex chromosomal pair, and NOR transposition, giving rise to the distinctive patterns observed among species/populations of Characidium. Biogeographic isolation and differentiation of sex chromosomes seem to have played a major role in the speciation process in this group of fish. PMID:21787398

  20. Protein kinase CK2 in human diseases

    DEFF Research Database (Denmark)

    Guerra, Barbara; Issinger, Olaf-Georg

    2008-01-01

    Protein kinase CK2 (formerly referred to as casein kinase II) is an evolutionary conserved, ubiquitous protein kinase. There are two paralog catalytic subunits, i.e. alpha (A1) and alpha' (A2). The alpha and alpha' subunits are linked to two beta subunits to produce a heterotetrameric structure....... The catalytic alpha subunits are distantly related to the CMGC subfamily of kinases, such as the Cdk kinases. There are some peculiarities associated with protein kinase CK2, which are not found with most other protein kinases: (i) the enzyme is constitutively active, (ii) it can use ATP and GTP and...... specifically target this protein kinase [10]. Since not all the aspects of what has been published on CK2 can be covered in this review, we would like to recommend the following reviews; (i) for general information on CK2 [11-18] and (ii) with a focus on aberrant CK2 [19-22]....

  1. Degradation of Activated Protein Kinases by Ubiquitination

    OpenAIRE

    Lu, Zhimin; Hunter, Tony

    2009-01-01

    Protein kinases are important regulators of intracellular signal transduction pathways and play critical roles in diverse cellular functions. Once a protein kinase is activated, its activity is subsequently downregulated through a variety of mechanisms. Accumulating evidence indicates that the activation of protein kinases commonly initiates their downregulation via the ubiquitin/proteasome pathway. Failure to regulate protein kinase activity or expression levels can cause human diseases.

  2. Determinants of homodimerization specificity in histidine kinases

    OpenAIRE

    Ashenberg, Orr; Rozen-Gagnon, Kathryn; Laub, Michael T; Keating, Amy E.

    2011-01-01

    Two-component signal transduction pathways consisting of a histidine kinase and a response regulator are used by prokaryotes to respond to diverse environmental and intracellular stimuli. Most species encode numerous paralogous histidine kinases that exhibit significant structural similarity. Yet in almost all known examples, histidine kinases are thought to function as homodimers. We investigated the molecular basis of dimerization specificity, focusing on the model histidine kinase EnvZ and...

  3. Non-disjunction of chromosome 13

    DEFF Research Database (Denmark)

    Bugge, Merete; Collins, Andrew; Hertz, Jens Michael;

    2007-01-01

    recombination in both maternal MI and MII errors and the former is associated with a significant number of tetrads (33%) that are nullichiasmate, which do not appear to be a feature of normal chromosome 13 meiosis. This study supports the evidence for subtle chromosome-specific influences on the mechanisms that...

  4. Chromosome number9 specific repetitive DNA sequence

    International Nuclear Information System (INIS)

    Human repetitive DNA libraries have been constructed and various recombinant DNA clones isolated that are likely candidates for chromosome specific sequences. The first clone tested (pHuR 98; plasmid human repeat 98) was biotinylated and hybridized to human chromosomes in situ. The hybridized recombinant probe was detected with fluoresceinated avidin, and chromosomes were counter-stained with either propidium iodide or distamycin-DAPI. Specific hybridization to chromosome band 9q1 was obtained. The localization was confirmed by hybridizing radiolabeled pHuR 98 DNA to human chromosomes sorted by flow cytometry. Various methods, including orthogonal field pulsed gel electrophoresis analysis indicate that 75 kilobase blocks of this sequence are interspersed with other repetitive DNA sequences in this chromosome band. This study is the first to report a human repetitive DNA sequence uniquely localized to a specific chromosome. This clone provides an easily detected and highly specific chromosomal marker for molecular cytogenetic analyses in numerous basic research and clinical studies

  5. Chromosomal characterization of Pseudonannolene strinatii (Spirostreptida, Pseudonannolenidae

    Directory of Open Access Journals (Sweden)

    Kleber Agari Campos

    2004-03-01

    Full Text Available The chromosomes of the cave millipede Pseudonannolene strinatii Mauriès, 1974 were investigated. The diploid chromosome number was found to be 2n=16, XX/XY; the C-banding technique revealed a large amount of heterochromatin while the silver staining technique (Ag-NOR evidenced the presence of heteromorphism of the NORs in some cells.

  6. 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.

  7. Mechanisms of Chromosome Number Evolution in Yeast

    Science.gov (United States)

    Gordon, Jonathan L.; Byrne, Kevin P.; Wolfe, Kenneth H.

    2011-01-01

    The whole-genome duplication (WGD) that occurred during yeast evolution changed the basal number of chromosomes from 8 to 16. However, the number of chromosomes in post-WGD species now ranges between 10 and 16, and the number in non-WGD species (Zygosaccharomyces, Kluyveromyces, Lachancea, and Ashbya) ranges between 6 and 8. To study the mechanism by which chromosome number changes, we traced the ancestry of centromeres and telomeres in each species. We observe only two mechanisms by which the number of chromosomes has decreased, as indicated by the loss of a centromere. The most frequent mechanism, seen 8 times, is telomere-to-telomere fusion between two chromosomes with the concomitant death of one centromere. The other mechanism, seen once, involves the breakage of a chromosome at its centromere, followed by the fusion of the two arms to the telomeres of two other chromosomes. The only mechanism by which chromosome number has increased in these species is WGD. Translocations and inversions have cycled telomere locations, internalizing some previously telomeric genes and creating novel telomeric locations. Comparison of centromere structures shows that the length of the CDEII region is variable between species but uniform within species. We trace the complete rearrangement history of the Lachancea kluyveri genome since its common ancestor with Saccharomyces and propose that its exceptionally low level of rearrangement is a consequence of the loss of the non-homologous end joining (NHEJ) DNA repair pathway in this species. PMID:21811419

  8. Genomic Dark Matter Illuminated: Anopheles Y Chromosomes.

    Science.gov (United States)

    Redmond, Seth N; Neafsey, Daniel E

    2016-08-01

    Hall et al. have strategically used long-read sequencing technology to characterize the structure and highly repetitive content of the Y chromosome in Anopheles malaria mosquitoes. Their work confirms that this important but elusive heterochromatic sex chromosome is evolving extremely rapidly and harbors a remarkably small number of genes. PMID:27263828

  9. Physical map of the Bacillus cereus chromosome.

    OpenAIRE

    Kolstø, A B; Grønstad, A; Oppegaard, H

    1990-01-01

    A physical map of the Bacillus cereus chromosome has been constructed by aligning 11 NotI fragments, ranging in size from 200 to 1,300 kilobases. The size of the chromosome is about 5.7 megabases. This is the first Bacillus genome of which a complete physical map has been described.

  10. Compositions for chromosome-specific staining

    Science.gov (United States)

    Gray, Joe W.; Pinkel, Daniel

    1998-01-01

    Methods and compositions for staining based upon nucleic acid sequence that employ nucleic acid probes are provided. Said methods produce staining patterns that can be tailored for specific cytogenetic analyses. Said probes are appropriate for in situ hybridization and stain both interphase and metaphase chromosomal material with reliable signals. The nucleic acid probes are typically of a complexity greater than 50 kb, the complexity depending upon the cytogenetic application. Methods are provided to disable the hybridization capacity of shared, high copy repetitive sequences and/or remove such sequences to provide for useful contrast. Still further methods are provided to produce chromosome-specific staining reagents which are made specific to the targeted chromosomal material, which can be one or more whole chromosomes, one or more regions on one or more chromosomes, subsets of chromosomes and/or the entire genome. Probes and test kits are provided for use in tumor cytogenetics, in the detection of disease related loci, in analysis of structural abnormalities, such as translocations, and for biological dosimetry. Further, methods and prenatal test kits are provided to stain targeted chromosomal material of fetal cells, including fetal cells obtained from maternal blood. Still further, the invention provides for automated means to detect and analyse chromosomal abnormalities.

  11. Evidence for linkage disequilibrium in chromosome 13-linked Duchenne-like muscular dystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Othmane, K.B.; Speer, M.C.; Stauffer, J. [Duke Univ. Medical Center, Durham, NC (United States)] [and others

    1995-09-01

    Duchenne-like muscular dystrophy (DLMD) is an autosomal recessive Limb Girdle muscular dystrophy (LGMD2C) characterized by late age of onset, proximal muscle weakness leading to disability, high creatine kinase values, normal intelligence and normal dystrophin in muscle biopsy. We have shown previously that three DLMD families from Tunisia are linked to chromosome 13q12. To further localize the LGMD2C gene, we have investigated seven additional families (119 individuals). Both genotyping and two-point linkage analysis were performed as described elsewhere. 7 refs., 1 fig., 1 tab.

  12. Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia or Chronic Myeloid Leukemia in Lymphoid Blast Crisis.

    Science.gov (United States)

    Kolenova, Alexandra; Maloney, Kelly W; Hunger, Stephen P

    2016-08-01

    The clinical characteristics of chronic myeloid leukemia (CML) in lymphoid blast crisis (BC) can resemble those of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph ALL). Because of this, there can be concern as to whether a patient with newly diagnosed Ph leukemia has Ph ALL or CML in lymphoid BC. This distinction has significant potential therapeutic implications because most children with Ph ALL are now treated with chemotherapy plus a tyrosine kinase inhibitor, whereas allogeneic stem cell transplant is usually recommended for any patient with CML that presents in or later develops BC. PMID:27164534

  13. Protein kinase TTK interacts and co-localizes with CENP-E to the kinetochore of human cells

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Spindle checkpoint is an important biochemical signaling cascade during mitosis which monitors the fidelity of chromosome segregation, and is mediated by protein kinases Mps1 and Bub1/BubR1. Our recent studies show that kinesin-related motor protein CENP-E interacts with BubR1 and participates in spindle checkpoint signaling. To elucidate the molecular mechanisms underlying spindle checkpoint signaling, we carried out proteomic dissection of human cell kinetochore and revealed protein kinase TTK, human homologue of yeast Mps1. Our studies show that TTK is localized to the kinetochore of human cells, and interacts with CENP-E, suggesting that TTK may play an important role in chromosome segregation during mitosis.

  14. Mapping of human chromosomal regions related to neoplasia: evidence from chromosomes 1 and 17

    Energy Technology Data Exchange (ETDEWEB)

    Rowley, J.D.

    1977-12-01

    In clonal aberrations leading to an excess or partial excess of chromosome I, trisomy for bands 1q25-1q32 was noted in the myeloid cells from all of 34 patients who had various disorders such as acute leukemia, polycythemia vera, and myelofibrosis. This was not the result of a particularly fragile site in that region of the chromosome because the break points in reciprocal translocations that involve it occurred almost exclusively in the short arm. Two consistent rearrangements that have been observed in chromosome 17 produced either duplication of the entire long arm or a translocation of the distal portion of the long arm to chromosome 15. The nonrandom chromosomal changes found in hematologic disorders can now be correlated with the gene loci on these chromosomes or chromosomal segments. Seventy-five genes related to various metabolic enzymes have been mapped; it may be significant that chromosomes carrying gene loci related to nucleic acid metabolism are more frequently involved in hematologic disorders (and other malignancies as well) than are gene loci related to intermediary or carbohydrate metabolism. Furthermore, the known virus-human chromosome associations are closely correlated with the chromosomes affected in hematologic disorders. If one of the effects of carcinogens (including viruses) is to activate genes that regulate host cell DNA synthesis, and if translocations or duplications of specific chromosomal segments produce the same effect, then either of these mechanisms might provide the affected cell with a proliferative advantage.

  15. Review of the Y chromosome and hypertension

    Directory of Open Access Journals (Sweden)

    D. Ely

    2000-06-01

    Full Text Available The Y chromosome from spontaneously hypertensive rats (SHR has a locus that raises blood pressure 20-25 mmHg. Associated with the SHR Y chromosome effect is a 4-week earlier pubertal rise of testosterone and dependence upon the androgen receptor for the full blood pressure effect. Several indices of enhanced sympathetic nervous system (SNS activity are also associated with the SHR Y chromosome. Blockade of SNS outflow reduced the blood pressure effect. Salt sensitivity was increased by the Y chromosome as was salt appetite which was SNS dependent. A strong correlation (r = 0.57, P<0.001 was demonstrable between plasma testosterone and angiotensin II. Coronary collagen increased with blood pressure and the presence of the SHR Y chromosome. A promising candidate gene for the Y effect is the Sry locus (testis determining factor, a transcription factor which may also have other functions.

  16. Genetic conflict and sex chromosome evolution

    Science.gov (United States)

    Meiklejohn, Colin D; Tao, Yun

    2009-01-01

    Chromosomal sex determination systems create the opportunity for the evolution of selfish genetic elements that increase the transmission of one sex chromosome at the expense of its homolog. Because such selfish elements on sex chromosomes can reduce fertility and distort the sex ratio of progeny, unlinked suppressors are expected to evolve, bringing different regions of the genome into conflict over the meiotic transmission of the sex chromosomes. Here we argue that recurrent genetic conflict over sex chromosome transmission is an important evolutionary force that has shaped a wide range of seemingly disparate phenomena including the epigenetic regulation of genes expressed in the germline, the distribution of genes in the genome, and the evolution of hybrid sterility between species. PMID:19931208

  17. Advances in understanding paternally transmitted Chromosomal Abnormalities

    Energy Technology Data Exchange (ETDEWEB)

    Marchetti, F; Sloter, E; Wyrobek, A J

    2001-03-01

    Multicolor FISH has been adapted for detecting the major types of chromosomal abnormalities in human sperm including aneuploidies for clinically-relevant chromosomes, chromosomal aberrations including breaks and rearrangements, and other numerical abnormalities. The various sperm FISH assays have been used to evaluate healthy men, men of advanced age, and men who have received mutagenic cancer therapy. The mouse has also been used as a model to investigate the mechanism of paternally transmitted genetic damage. Sperm FISH for the mouse has been used to detect chromosomally abnormal mouse sperm, while the PAINT/DAPI analysis of mouse zygotes has been used to evaluate the types of chromosomal defects that can be paternally transmitted to the embryo and their effects on embryonic development.

  18. Antineoplastic effects of an Aurora B kinase inhibitor in breast cancer

    Directory of Open Access Journals (Sweden)

    Velazquez-Torres Guermarie

    2010-02-01

    Full Text Available Abstract Background Aurora B kinase is an important mitotic kinase involved in chromosome segregation and cytokinesis. It is overexpressed in many cancers and thus may be an important molecular target for chemotherapy. AZD1152 is the prodrug for AZD1152-HQPA, which is a selective inhibitor of Aurora B kinase activity. Preclinical antineoplastic activity of AZD1152 against acute myelogenous leukemia, multiple myeloma and colorectal cancer has been reported. However, this compound has not been evaluated in breast cancer, the second leading cause of cancer deaths among women. Results The antineoplastic activity of AZD1152-HQPA in six human breast cancer cell lines, three of which overexpress HER2, is demonstrated. AZD1152-HQPA specifically inhibited Aurora B kinase activity in breast cancer cells, thereby causing mitotic catastrophe, polyploidy and apoptosis, which in turn led to apoptotic death. AZD1152 administration efficiently suppressed the tumor growth in a breast cancer cell xenograft model. In addition, AZD1152 also inhibited pulmonary metastatic nodule formation in a metastatic breast cancer model. Notably, it was also found that the protein level of Aurora B kinase declined after inhibition of Aurora B kinase activity by AZD1152-HQPA in a time- and dose-dependent manner. Investigation of the underlying mechanism suggested that AZD1152-HQPA accelerated protein turnover of Aurora B via enhancing its ubiquitination. Conclusions It was shown that AZD1152 is an effective antineoplastic agent for breast cancer, and our results define a novel mechanism for posttranscriptional regulation of Aurora B after AZD1152 treatment and provide insight into dosing regimen design for this kinase inhibitor in metastatic breast cancer treatment.

  19. New Y chromosomes and early stages of sex chromosome differentiation: sex determination in Megaselia

    Indian Academy of Sciences (India)

    Walther Traut

    2010-09-01

    The phorid fly Megaselia scalaris is a laboratory model for the turnover and early differentiation of sex chromosomes. Isolates from the field have an XY sex-determining mechanism with chromosome pair 2 acting as X and Y chromosomes. The sex chromosomes are homomorphic but display early signs of sex chromosome differentiation: a low level of molecular differences between X and Y. The male-determining function $(M)$, maps to the distal part of the Y chromosome’s short arm. In laboratory cultures, new Y chromosomes with no signs of a molecular differentiation arise at a low rate, probably by transposition of to these chromosomes. Downstream of the primary signal, the homologue of the Drosophila doublesex (dsx) is part of the sex-determining pathway while Sex-lethal (Sxl), though structurally conserved, is not.

  20. Y-chromosome evolution: emerging insights into processes of Y-chromosome degeneration.

    Science.gov (United States)

    Bachtrog, Doris

    2013-02-01

    The human Y chromosome is intriguing not only because it harbours the master-switch gene that determines gender but also because of its unusual evolutionary history. The Y chromosome evolved from an autosome, and its evolution has been characterized by massive gene decay. Recent whole-genome and transcriptome analyses of Y chromosomes in humans and other primates, in Drosophila species and in plants have shed light on the current gene content of the Y chromosome, its origins and its long-term fate. Furthermore, comparative analysis of young and old Y chromosomes has given further insights into the evolutionary and molecular forces triggering Y-chromosome degeneration and into the evolutionary destiny of the Y chromosome. PMID:23329112

  1. Novel gene acquisition on carnivore Y chromosomes.

    Directory of Open Access Journals (Sweden)

    2006-03-01

    Full Text Available Despite its importance in harboring genes critical for spermatogenesis and male-specific functions, the Y chromosome has been largely excluded as a priority in recent mammalian genome sequencing projects. Only the human and chimpanzee Y chromosomes have been well characterized at the sequence level. This is primarily due to the presumed low overall gene content and highly repetitive nature of the Y chromosome and the ensuing difficulties using a shotgun sequence approach for assembly. Here we used direct cDNA selection to isolate and evaluate the extent of novel Y chromosome gene acquisition in the genome of the domestic cat, a species from a different mammalian superorder than human, chimpanzee, and mouse (currently being sequenced. We discovered four novel Y chromosome genes that do not have functional copies in the finished human male-specific region of the Y or on other mammalian Y chromosomes explored thus far. Two genes are derived from putative autosomal progenitors, and the other two have X chromosome homologs from different evolutionary strata. All four genes were shown to be multicopy and expressed predominantly or exclusively in testes, suggesting that their duplication and specialization for testis function were selected for because they enhance spermatogenesis. Two of these genes have testis-expressed, Y-borne copies in the dog genome as well. The absence of the four newly described genes on other characterized mammalian Y chromosomes demonstrates the gene novelty on this chromosome between mammalian orders, suggesting it harbors many lineage-specific genes that may go undetected by traditional comparative genomic approaches. Specific plans to identify the male-specific genes encoded in the Y chromosome of mammals should be a priority.

  2. Chromosome differentiation patterns during cichlid fish evolution

    Directory of Open Access Journals (Sweden)

    Nirchio Mauro

    2010-06-01

    Full Text Available Abstract Background Cichlid fishes have been the subject of increasing scientific interest because of their rapid adaptive radiation which has led to an extensive ecological diversity and their enormous importance to tropical and subtropical aquaculture. To increase our understanding of chromosome evolution among cichlid species, karyotypes of one Asian, 22 African, and 30 South American cichlid species were investigated, and chromosomal data of the family was reviewed. Results Although there is extensive variation in the karyotypes of cichlid fishes (from 2n = 32 to 2n = 60 chromosomes, the modal chromosome number for South American species was 2n = 48 and the modal number for the African ones was 2n = 44. The only Asian species analyzed, Etroplus maculatus, was observed to have 46 chromosomes. The presence of one or two macro B chromosomes was detected in two African species. The cytogenetic mapping of 18S ribosomal RNA (18S rRNA gene revealed a variable number of clusters among species varying from two to six. Conclusions The karyotype diversification of cichlids seems to have occurred through several chromosomal rearrangements involving fissions, fusions and inversions. It was possible to identify karyotype markers for the subfamilies Pseudocrenilabrinae (African and Cichlinae (American. The karyotype analyses did not clarify the phylogenetic relationship among the Cichlinae tribes. On the other hand, the two major groups of Pseudocrenilabrinae (tilapiine and haplochromine were clearly discriminated based on the characteristics of their karyotypes. The cytogenetic mapping of 18S ribosomal RNA (18S rRNA gene did not follow the chromosome diversification in the family. The dynamic evolution of the repeated units of rRNA genes generates patterns of chromosomal distribution that do not help follows the phylogenetic relationships among taxa. The presence of B chromosomes in cichlids is of particular interest because they may not be represented in

  3. Integrin-linked kinase regulates interphase and mitotic microtubule dynamics.

    Directory of Open Access Journals (Sweden)

    Simin Lim

    Full Text Available Integrin-linked kinase (ILK localizes to both focal adhesions and centrosomes in distinct multiprotein complexes. Its dual function as a kinase and scaffolding protein has been well characterized at focal adhesions, where it regulates integrin-mediated cell adhesion, spreading, migration and signaling. At the centrosomes, ILK regulates mitotic spindle organization and centrosome clustering. Our previous study showed various spindle defects after ILK knockdown or inhibition that suggested alteration in microtubule dynamics. Since ILK expression is frequently elevated in many cancer types, we investigated the effects of ILK overexpression on microtubule dynamics. We show here that overexpressing ILK in HeLa cells was associated with a shorter duration of mitosis and decreased sensitivity to paclitaxel, a chemotherapeutic agent that suppresses microtubule dynamics. Measurement of interphase microtubule dynamics revealed that ILK overexpression favored microtubule depolymerization, suggesting that microtubule destabilization could be the mechanism behind the decreased sensitivity to paclitaxel, which is known to stabilize microtubules. Conversely, the use of a small molecule inhibitor selective against ILK, QLT-0267, resulted in suppressed microtubule dynamics, demonstrating a new mechanism of action for this compound. We further show that treatment of HeLa cells with QLT-0267 resulted in higher inter-centromere tension in aligned chromosomes during mitosis, slower microtubule regrowth after cold depolymerization and the presence of a more stable population of spindle microtubules. These results demonstrate that ILK regulates microtubule dynamics in both interphase and mitotic cells.

  4. Polo-like kinase I controls nuclear envelope break down and chromosome dynamics in meiosis I

    Czech Academy of Sciences Publication Activity Database

    Šolc, Petr; Kitajima, T.; Baran, V.; Brzáková, Adéla; Mayer, Alexandra; Šámalová, P.; Motlík, Jan; Ellenberg, J.

    2012-01-01

    Roč. 58, Suppl (2012), 66-66. ISSN 0916-8818. [Japan-Czech Joint Symposium/2./. 10.09.2012-10.09.2012, Tokyo] R&D Projects: GA ČR(CZ) GC301/09/J036; GA ČR(CZ) GPP301/11/P081 Institutional support: RVO:67985904 Keywords : PLK1 Subject RIV: EB - Genetics ; Molecular Biology

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

    OpenAIRE

    Yerle Martine; Ducos Alain; Pinton Alain

    2003-01-01

    Abstract A pericentric inversion of chromosome 4 in a boar, as well as a case of (2q-;5p+) translocation mosaicism in a bull were analysed by chromosome painting using probes generated by conventional microdissection. For the porcine inversion, probes specific for p arms and q arms were produced and hybridised simultaneously on metaphases of a heterozygote carrier. In the case of the bovine translocation, two whole chromosome probes (chromosome 5, and derived chromosome 5) were elaborated and...

  6. Sex chromosome evolution: platypus gene mapping suggests that part of the human X chromosome was originally autosomal.

    OpenAIRE

    Watson, J M; Spencer, J. A.; Riggs, A D; Graves, J.A.

    1991-01-01

    To investigate the evolution of the mammalian sex chromosomes, we have compared the gene content of the X chromosomes in the mammalian groups most distantly related to man (marsupials and monotremes). Previous work established that genes on the long arm of the human X chromosome are conserved on the X chromosomes in all mammals, revealing that this region was part of an ancient mammalian X chromosome. However, we now report that several genes located on the short arm of the human X chromosome...

  7. DMPD: Bruton's tyrosine kinase (Btk)-the critical tyrosine kinase in LPS signalling? [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 15081522 Bruton's tyrosine kinase (Btk)-the critical tyrosine kinase in LPS signall...ruton's tyrosine kinase (Btk)-the critical tyrosine kinase in LPS signalling? PubmedID 15081522 Title Bruton...'s tyrosine kinase (Btk)-the critical tyrosine kinase in LPS signalling? Authors

  8. Nonrandom chromosomal changes in human malignant cells

    Energy Technology Data Exchange (ETDEWEB)

    Rowley, J D

    1977-01-01

    The role of chromosomal changes in human malignant cells has been the subject of much debate. The observation of nonrandom chromosomal changes has become well recognized in chronic myelogenous leukemia, and more recently in acute myelogenous leukemia. In the present report, data are presented on the sites of duplication of chromosome No. 1 in hematologic disorders. Trisomy for region lq25 to lq32 was observed in every one of 34 patients whose cells showed duplication of some part of chromosome No. 1. Adjacent regions lq21 to lq25, and lq32 to lqter, also were trisomic in the majority of patients. Two patients had deletions, one of lq32 to qter, and the other, of lp32 to pter. The sites of chromosomal breaks leading to trisomy differ from those involved in balanced reciprocal translocations. Some of these sites are sometimes, but not always, vulnerable in constitutional chromosomal abnormalities. The nature of the proliferative advantage conferred on myeloid cells by these chromosomal changes is unknown.

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

    Science.gov (United States)

    Lukhtanov, Vladimir A

    2014-01-01

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

  10. Chromosome number evolution in skippers (Lepidoptera, Hesperiidae

    Directory of Open Access Journals (Sweden)

    Vladimir Lukhtanov

    2014-11-01

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

  11. Group 3 chromosome bin maps of wheat and their relationship to rice chromosome 1.

    Science.gov (United States)

    Munkvold, J D; Greene, R A; Bermudez-Kandianis, C E; La Rota, C M; Edwards, H; Sorrells, S F; Dake, T; Benscher, D; Kantety, R; Linkiewicz, A M; Dubcovsky, J; Akhunov, E D; Dvorák, J; Miftahudin; Gustafson, J P; Pathan, M S; Nguyen, H T; Matthews, D E; Chao, S; Lazo, G R; Hummel, D D; Anderson, O D; Anderson, J A; Gonzalez-Hernandez, J L; Peng, J H; Lapitan, N; Qi, L L; Echalier, B; Gill, B S; Hossain, K G; Kalavacharla, V; Kianian, S F; Sandhu, D; Erayman, M; Gill, K S; McGuire, P E; Qualset, C O; Sorrells, M E

    2004-10-01

    The focus of this study was to analyze the content, distribution, and comparative genome relationships of 996 chromosome bin-mapped expressed sequence tags (ESTs) accounting for 2266 restriction fragments (loci) on the homoeologous group 3 chromosomes of hexaploid wheat (Triticum aestivum L.). Of these loci, 634, 884, and 748 were mapped on chromosomes 3A, 3B, and 3D, respectively. The individual chromosome bin maps revealed bins with a high density of mapped ESTs in the distal region and bins of low density in the proximal region of the chromosome arms, with the exception of 3DS and 3DL. These distributions were more localized on the higher-resolution group 3 consensus map with intermediate regions of high-mapped-EST density on both chromosome arms. Gene ontology (GO) classification of mapped ESTs was not significantly different for homoeologous group 3 chromosomes compared to the other groups. A combined analysis of the individual bin maps using 537 of the mapped ESTs revealed rearrangements between the group 3 chromosomes. Approximately 232 (44%) of the consensus mapped ESTs matched sequences on rice chromosome 1 and revealed large- and small-scale differences in gene order. Of the group 3 mapped EST unigenes approximately 21 and 32% matched the Arabidopsis coding regions and proteins, respectively, but no chromosome-level gene order conservation was detected. PMID:15514041

  12. Chromosome heteromorphism quantified by high-resolution bivariate flow karyotyping.

    Science.gov (United States)

    Trask, B; van den Engh, G; Mayall, B; Gray, J W

    1989-11-01

    Maternal and paternal homologues of many chromosome types can be differentiated on the basis of their peak position in Hoechst 33258 versus chromomycin A3 bivariate flow karyotypes. We demonstrate here the magnitude of DNA content differences among normal chromosomes of the same type. Significant peak-position differences between homologues were observed for an average of four chromosome types in each of the karyotypes of 98 different individuals. The frequency of individuals with differences in homologue peak positions varied among chromosome types: e.g., chromosome 15, 61%; chromosome 3, 4%. Flow karyotypes of 33 unrelated individuals were compared to determine the range of peak position among normal chromosomes. Chromosomes Y, 21, 22, 15, 16, 13, 14, and 19 were most heteromorphic, and chromosomes 2-8 and X were least heteromorphic. The largest chromosome 21 was 45% larger than the smallest 21 chromosome observed. The base composition of the variable regions differed among chromosome types. DNA contents of chromosome variants determined from flow karyotypes were closely correlated to measurements of DNA content made of gallocyanin chrome alum-stained metaphase chromosomes on slides. Fluorescence in situ hybridization with chromosome-specific repetitive sequences indicated that variability in their copy number is partly responsible for peak-position variability in some chromosomes. Heteromorphic chromosomes are identified for which parental flow karyotype information will be essential if de novo rearrangements resulting in small DNA content changes are to be detected with flow karyotyping. PMID:2479266

  13. Adaptation through chromosomal inversions in Anopheles

    Directory of Open Access Journals (Sweden)

    Diego eAyala

    2014-05-01

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

  14. RIP Kinases Initiate Programmed Necrosis

    Institute of Scientific and Technical Information of China (English)

    Lorenzo Galluzzi; Oliver Kepp; Guido Kroemer

    2009-01-01

    Some lethal stimuli can induce either apoptosis or necrosis, depending on the cell type and/or experimental setting. Until recently,the molecular bases of this phenomenon were largely unknown. Now, two members of the receptor-interacting serine-threonine kinase (RIP) family, RIP1 and RIP3, have been demonstrated to control the switch between apoptotic and necrotic cell death.Some mechanistic details, however, remain controversial.

  15. Thymidine kinase diversity in bacteria

    DEFF Research Database (Denmark)

    Sandrini, Michael; Clausen, A.R.; Munch-Petersen, B.;

    2006-01-01

    Thymidine kinases (TKs) appear to be almost ubiquitous and are found in nearly all prokaryotes, eukaryotes, and several viruses. They are the key enzymes in thymidine salvage and activation of several anti-cancer and antiviral drugs. We show that bacterial TKs can be subdivided into 2 groups. The...... TKs from Gram-positive bacteria are more closely related to the eukaryotic TK1 enzymes than are TKs from Gram-negative bacteria....

  16. Pantothenate Kinase-Associated Neurodegeneration

    OpenAIRE

    Meitinger, Thomas; Prokisch, Holger; Hartig, Monika B.; Klopstock, Thomas

    2012-01-01

    Pantothenate kinase-associated neurodegeneration (PKAN) is a hereditary progressive disorder and the most frequent form of neurodegeneration with brain iron accumulation (NBIA). PKAN patients present with a progressive movement disorder, dysarthria, cognitive impairment and retinitis pigmentosa. In magnetic resonance imaging, PKAN patients exhibit the pathognonomic "eye of the tiger" sign in the globus pallidus which corresponds to iron accumulation and gliosis as shown in neuropathological e...

  17. Oncoprotein protein kinase antibody kit

    Science.gov (United States)

    Karin, Michael; Hibi, Masahiko; Lin, Anning

    2008-12-23

    An isolated polypeptide (JNK) characterized by having a molecular weight of 46 kD as determined by reducing SDS-PAGE, having serine and threonine kinase activity, phosphorylating the c-Jun N-terminal activation domain and polynucleotide sequences and method of detection of JNK are provided herein. JNK phosphorylates c-Jun N-terminal activation domain which affects gene expression from AP-1 sites.

  18. Thymidine kinase diversity in bacteria

    DEFF Research Database (Denmark)

    Sandrini, Michael; Clausen, A.R.; Munch-Petersen, B.; Piskur, Jure

    Thymidine kinases (TKs) appear to be almost ubiquitous and are found in nearly all prokaryotes, eukaryotes, and several viruses. They are the key enzymes in thymidine salvage and activation of several anti-cancer and antiviral drugs. We show that bacterial TKs can be subdivided into 2 groups. The...... TKs from Gram-positive bacteria are more closely related to the eukaryotic TK1 enzymes than are TKs from Gram-negative bacteria....

  19. Regulation and function of TPL-2,an IκB kinase-regulated MAP kinase kinase kinase

    Institute of Scientific and Technical Information of China (English)

    Thorsten Gantke; Srividya Sriskantharajah; Steven C Ley

    2011-01-01

    The IκB kinase(IKK)complex plays a well-documented role in innate and adaptive immunity.This function has been widely attributed to its role as the central activator of the NF-κB family of transcription factors.However,another important consequence of IKK activation is the regulation of TPL-2,a MEK kinase that is required for activation of ERK-1/2 MAP kinases in myeioid cells following Toll-like receptor and TNF receptor stimulation.In unstimulated cells,TPL-2 is stoichiometrically complexed with the NF-κB inhibitory protein NF-κB1 p105,which blocks TPL-2 access to its substrate MEK,and the ubiquitin-binding protein ABIN-2(A20-binding inhibitor of NF-κB 2),both of which are required to maintain TPL-2 protein stability.Following agonist stimulation,the IKK complex phosphorylates p105,triggering its K48-1inked ubiquitination and degradation by the proteasome.This releases TPL-2 from p105-mediated inhibition,facilitating activation of MEK,in addition to modulating NF-κB activation by liberating associated Rel subunits for translocation into the nucleus.IKK-induced proteolysis of 0105,therefore,can directly regulate both NF-κB and ERK MAP kinase activation via NF-κB1 p105.TPL-2 is critical for production of the proinflammatory cytokine TNF during inflammatory responses.Consequently,there has been considerable interest in the pharmaceutical industry to develop selective TPL-2 inhibitors as drugs for the treatment of TNF-dependent inflammatory,diseases,such as rheumatoid arthritis and inflammatory bowel disease.This review summarizes our current understanding of the regulation of TPL-2 signaling function,and also the complex positive and negative roles of TPL-2 in immune and inflammatory responses.

  20. 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

  1. A proteomic approach for comprehensively screening substrates of protein kinases such as Rho-kinase.

    Directory of Open Access Journals (Sweden)

    Mutsuki Amano

    Full Text Available BACKGROUND: Protein kinases are major components of signal transduction pathways in multiple cellular processes. Kinases directly interact with and phosphorylate downstream substrates, thus modulating their functions. Despite the importance of identifying substrates in order to more fully understand the signaling network of respective kinases, efficient methods to search for substrates remain poorly explored. METHODOLOGY/PRINCIPAL FINDINGS: We combined mass spectrometry and affinity column chromatography of the catalytic domain of protein kinases to screen potential substrates. Using the active catalytic fragment of Rho-kinase/ROCK/ROK as the model bait, we obtained about 300 interacting proteins from the rat brain cytosol fraction, which included the proteins previously reported as Rho-kinase substrates. Several novel interacting proteins, including doublecortin, were phosphorylated by Rho-kinase both in vitro and in vivo. CONCLUSIONS/SIGNIFICANCE: This method would enable identification of novel specific substrates for kinases such as Rho-kinase with high sensitivity.

  2. Chromosome landmarks and autosome-sex chromosome translocations in Rumex hastatulus, a plant with XX/XY1Y2 sex chromosome system.

    Science.gov (United States)

    Grabowska-Joachimiak, Aleksandra; Kula, Adam; Książczyk, Tomasz; Chojnicka, Joanna; Sliwinska, Elwira; Joachimiak, Andrzej J

    2015-06-01

    Rumex hastatulus is the North American endemic dioecious plant with heteromorphic sex chromosomes. It is differentiated into two chromosomal races: Texas (T) race characterised by a simple XX/XY sex chromosome system and North Carolina (NC) race with a polymorphic XX/XY1Y2 sex chromosome system. The gross karyotype morphology in NC race resembles the derived type, but chromosomal changes that occurred during its evolution are poorly understood. Our C-banding/DAPI and fluorescence in situ hybridization (FISH) experiments demonstrated that Y chromosomes of both races are enriched in DAPI-positive sequences and that the emergence of polymorphic sex chromosome system was accompanied by the break of ancestral Y chromosome and switch in the localization of 5S rDNA, from autosomes to sex chromosomes (X and Y2). Two contrasting domains were detected within North Carolina Y chromosomes: the older, highly heterochromatinised, inherited from the original Y chromosome and the younger, euchromatic, representing translocated autosomal material. The flow-cytometric DNA estimation showed ∼3.5 % genome downsizing in the North Carolina race. Our results are in contradiction to earlier reports on the lack of heterochromatin within Y chromosomes of this species and enable unambiguous identification of autosomes involved in the autosome-heterosome translocation, providing useful chromosome landmarks for further studies on the karyotype and sex chromosome differentiation in this species. PMID:25394583

  3. Visualization of yeast chromosomal DNA

    Science.gov (United States)

    Lubega, Seth

    1990-01-01

    The DNA molecule is the most significant life molecule since it codes the blue print for other structural and functional molecules of all living organisms. Agarose gel electrophoresis is now being widely used to separate DNA of virus, bacteria, and lower eukaryotes. The task was undertaken of reviewing the existing methods of DNA fractionation and microscopic visualization of individual chromosonal DNA molecules by gel electrophoresis as a basis for a proposed study to investigate the feasibility of separating DNA molecules in free fluids as an alternative to gel electrophoresis. Various techniques were studied. On the molecular level, agarose gel electrophoresis is being widely used to separate chromosomal DNA according to molecular weight. Carl and Olson separate and characterized the entire karyotype of a lab strain of Saccharomyces cerevisiae. Smith et al. and Schwartz and Koval independently reported the visualization of individual DNA molecules migrating through agarose gel matrix during electrophoresis. The techniques used by these researchers are being reviewed in the lab as a basis for the proposed studies.

  4. Dynamic changes in paternal X-chromosome activity during imprinted X-chromosome inactivation in mice

    OpenAIRE

    Patrat, Catherine; Okamoto, Ikuhiro; Diabangouaya, Patricia; Vialon, Vivian; Le Baccon, Patricia; Chow, Jennifer; Heard, Edith

    2009-01-01

    In mammals, X-chromosome dosage compensation is achieved by inactivating one of the two X chromosomes in females. In mice, X inactivation is initially imprinted, with inactivation of the paternal X (Xp) chromosome occurring during preimplantation development. One theory is that the Xp is preinactivated in female embryos, because of its previous silence during meiosis in the male germ line. The extent to which the Xp is active after fertilization and the exact time of onset of X-linked gene si...

  5. Tracking Chromosome Evolution in Southern African Gerbils Using Flow-Sorted Chromosome Paints

    OpenAIRE

    Knight, L.I.; Ng, B. L.; Cheng, W; Fu, B.; Yang, F.; Rambau, R V

    2013-01-01

    Desmodillus and Gerbilliscus (formerly Tatera) comprise a monophyletic group of gerbils (subfamily Gerbillinae) which last shared an ancestor approximately 8 million years ago; diploid chromosome number variation among the species ranges from 2n = 36 to 2n = 50. In an attempt to shed more light on chromosome evolution and speciation in these rodents, we compared the karyotypes of 7 species, representing 3 genera, based on homology data revealed by chromosome painting with probes derived from ...

  6. Sex Chromosome Evolution in Amniotes: Applications for Bacterial Artificial Chromosome Libraries

    OpenAIRE

    Janes, Daniel E.; Nicole Valenzuela; Tariq Ezaz; Chris Amemiya; Edwards, Scott V.

    2011-01-01

    Variability among sex chromosome pairs in amniotes denotes a dynamic history. Since amniotes diverged from a common ancestor, their sex chromosome pairs and, more broadly, sex-determining mechanisms have changed reversibly and frequently. These changes have been studied and characterized through the use of many tools and experimental approaches but perhaps most effectively through applications for bacterial artificial chromosome (BAC) libraries. Individual BAC clones carry 100–200 kb of seque...

  7. Haploidization via Chromosome Elimination: Means and Mechanisms.

    Science.gov (United States)

    Ishii, Takayoshi; Karimi-Ashtiyani, Raheleh; Houben, Andreas

    2016-04-29

    The ability to generate haploids and subsequently induce chromosome doubling significantly accelerates the crop breeding process. Haploids have been induced through the generation of plants from haploid tissues (in situ gynogenesis and androgenesis) and through the selective loss of a parental chromosome set via inter- or intraspecific hybridization. Here, we focus on the mechanisms responsible for this selective chromosome elimination. CENH3, a variant of the centromere-specific histone H3, has been exploited to create an efficient method of haploid induction, and we discuss this approach in some detail. Parallels have been drawn with chromosome-specific elimination, which occurs as a normal part of differentiation and sex determination in many plant and animal systems. PMID:26772657

  8. Cancer chromosomal instability: therapeutic and diagnostic challenges

    OpenAIRE

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

    2012-01-01

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

  9. Lattice animal model of chromosome organization

    Science.gov (United States)

    Iyer, Balaji V. S.; Arya, Gaurav

    2012-07-01

    Polymer models tied together by constraints of looping and confinement have been used to explain many of the observed organizational characteristics of interphase chromosomes. Here we introduce a simple lattice animal representation of interphase chromosomes that combines the features of looping and confinement constraints into a single framework. We show through Monte Carlo simulations that this model qualitatively captures both the leveling off in the spatial distance between genomic markers observed in fluorescent in situ hybridization experiments and the inverse decay in the looping probability as a function of genomic separation observed in chromosome conformation capture experiments. The model also suggests that the collapsed state of chromosomes and their segregation into territories with distinct looping activities might be a natural consequence of confinement.

  10. Chromosome studies in the genus Jatropha L.

    Directory of Open Access Journals (Sweden)

    R.Sasikala and M.Paramathma

    2010-07-01

    Full Text Available The inflorescences of ten species of the genus Jatropha were fixed in Cornoy’s fluid (6:3:1. Acetocarmine stain (2% wasused for staining the pollen mother cells. Seven species exhibited 11 bivalents and 2n =22 and x=11. But the two otherspecies, J.villosa var. villosa and J.villosa var. ramnadensis showed only 10 bivalents and 2n number of 20 chromosomesand x=10. The study concluded the occurrence of two kinds of haploid chromosome numbers of n =10 and n =11. ExceptJatropha tanjorensis, cytological investigation in all species exhibited normal and complete pairing and bivalent formationin metaphase I and equal separation of chromosome in anaphase and indicated that the course of meiosis was normal.Jatropha tanjorensis did not exhibit normal course of meiosis and no proper count of chromosomes could be made. Presentchromosomal studies in Jatropha revealed the existence of two basic chromosomes numbers x = 5 and x = 6.

  11. System for the analysis of plant chromosomes

    International Nuclear Information System (INIS)

    The paper describes a computer system for the automation workers of recognition analysis and interpretation of plant chromosomes. This system permit to carry out the analysis in a more comfortable and faster way, using the image processing techniques

  12. Immunochemical characterization of rat brain protein kinase

    International Nuclear Information System (INIS)

    Polyclonal antibodies against rat brain protein kinase C (the Ca2+/phospholipid-dependent enzyme) were raised in goat. These antibodies can neutralize completely the kinase activity in purified enzyme preparation as well as that in the crude homogenate. Immunoblot analysis of the purified and the crude protein kinase C preparations revealed a major immunoreactive band of 80 kDa. The antibodies also recognize the same enzyme from other rat tissues. Neuronal tissues (cerebral cortex, cerebellum, hypothalamus, and retina) and lymphoid organs (thymus and spleen) were found to be enriched in protein kinase C, whereas lung, kidney, liver, heart, and skeletal muscle contained relatively low amounts of this kinase. Limited proteolysis of the purified rat brain protein kinase C with trypsin results in an initial degradation of the kinase into two major fragments of 48 and 38 kDa. Both fragments are recognized by the antibodies. However, further digestion of the 48-kDa fragment to 45 kDa and the 38-kDa fragment to 33 kDa causes a loss of the immunoreactivity. Upon incubation of the cerebellar extract with Ca2+, the 48-kDa fragment was also identified as a major proteolytic product of protein kinase C. Proteolytic degradation of protein kinase C converts the Ca2+/phospholipid-dependent kinase to an independent form without causing a large impairment of the binding of [3H]phorbol 12,13-dibutyrate. The two major proteolytic fragments were separated by ion exchange chromatography and one of them (45-48 kDa) was identified as a protein kinase and the other (33-38 kDa) as a phorbol ester-binding protein. These results demonstrate that rat brain protein kinase C is composed of two functionally distinct units, namely, a protein kinase and a Ca2+-independent/phospholipid-dependent phorbol ester-binding protein

  13. Positive and negative regulation of radiation-induced apoptosis by protein kinase C

    International Nuclear Information System (INIS)

    Indicators such as clonogenic survival, transformation, and chromosomal aberrations are used to evaluate the effects of radiation on cells. Apoptosis, another such indicator, is a mode of cell death, and radiation-induced apoptosis contributes to eliminating damaged cells and preventing malformation and carcinogenesis. Understanding radiation-induced apoptosis will assist in radiotherapy for cancer and treatment of patients in accidental radiation exposure. Protein kinase C (PKC) is a serine/threonine kinase that is related to cell proliferation, differentiation, metabolism, and apoptosis, and has many roles in the radiation-induced cellular responses involving apoptosis. This review describes the functions of PKC, including its relationship with other signaling networks and oxidative stress in the regulation of radiation-induced apoptosis. Such information might provide clues for evaluating the effects of radiation and for identifying clinical applications. (author)

  14. Functional cooperation of Dam1, Ipl1, and the inner centromere protein (INCENP)–related protein Sli15 during chromosome segregation

    OpenAIRE

    Kang, Jung-seog; Cheeseman, Iain M.; Kallstrom, George; Velmurugan, Soundarapandian; Barnes, Georjana; Chan, Clarence S.M.

    2001-01-01

    We have shown previously that Ipl1 and Sli15 are required for chromosome segregation in Saccharomyces cerevisiae. Sli15 associates directly with the Ipl1 protein kinase and these two proteins colocalize to the mitotic spindle. We show here that Sli15 stimulates the in vitro, and likely in vivo, kinase activity of Ipl1, and Sli15 facilitates the association of Ipl1 with the mitotic spindle. The Ipl1-binding and -stimulating activities of Sli15 both reside within a region containing homology to...

  15. X rays induce interallelic homologous recombination at the human thymidine kinase gene.

    OpenAIRE

    Benjamin, M B; Little, J B

    1992-01-01

    We have developed a human lymphoblast cell line for the study of interchromosomal homologous recombination at the endogenous thymidine kinase (tk) gene on chromosome 17 (M. B. Benjamin, H. Potter, D. W. Yandell, and J. B. Little, Proc. Natl. Acad. Sci. USA 88:6652-6656, 1991). This cell line (designated 6:86) carries unique heterozygous frameshift mutations in exons 4 and 7 of its endogenous tk alleles and can revert to TK+ by frame-restoring mutations, gene conversion, or reciprocal recombin...

  16. Targetable kinase-activating lesions in Ph-like acute lymphoblastic leukemia | Office of Cancer Genomics

    Science.gov (United States)

    Publication Abstract:  Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is characterized by a gene-expression profile similar to that of BCR-ABL1-positive ALL, alterations of lymphoid transcription factor genes, and a poor outcome. The frequency and spectrum of genetic alterations in Ph-like ALL and its responsiveness to tyrosine kinase inhibition are undefined, especially in adolescents and adults. We performed genomic profiling of 1725 patients with precursor B-cell ALL and detailed genomic analysis of 154 patients with Ph-like ALL.

  17. Label Free Chromosome Translocation Detection with Silicon nanowires

    DEFF Research Database (Denmark)

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

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

  18. Methods and compositions for chromosome-specific staining

    Science.gov (United States)

    Gray, Joe W.; Pinkel, Daniel

    2003-07-22

    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.

  19. The hierarchically organized splitting of chromosomal bands for all human chromosomes

    Directory of Open Access Journals (Sweden)

    Liehr Thomas

    2009-01-01

    Full Text Available Abstract Background Chromosome banding is widely used in cytogenetics. However, the biological nature of hierarchically organized splitting of chromosomal bands of human chromosomes is an enigma and has not been, as yet, studied. Results Here we present for the first time the hierarchically organized splitting of chromosomal bands in their sub-bands for all human chromosomes. To do this, array-proved multicolor banding (aMCB probe-sets for all human chromosomes were applied to normal metaphase spreads of three different G-band levels. We confirmed for all chromosomes to be a general principle that only Giemsa-dark bands split into dark and light sub-bands, as we demonstrated previously by chromosome stretching. Thus, the biological band splitting is in > 50% of the sub-bands different than implemented by the ISCN nomenclature suggesting also a splitting of G-light bands. Locus-specific probes exemplary confirmed the results of MCB. Conclusion Overall, the present study enables a better understanding of chromosome architecture. The observed difference of biological and ISCN band-splitting may be an explanation why mapping data from human genome project do not always fit the cytogenetic mapping.

  20. Y chromosome evolution: emerging insights into processes of Y chromosome degeneration

    Science.gov (United States)

    Bachtrog, Doris

    2014-01-01

    The human Y chromosome is intriguing not only because it harbours the master-switch gene determining gender but also because of its unusual evolutionary trajectory. Previously an autosome, Y chromosome evolution has been characterized by massive gene decay. Recent whole-genome and transcriptome analyses of Y chromosomes in humans and other primates, in Drosophila species as well as in plants have shed light on the current gene content of the Y, its origins and its long-term fate. Comparative analysis of young and old Y chromosomes have given further insights into the evolutionary and molecular forces triggering Y degeneration and its evolutionary destiny. PMID:23329112

  1. Localization of topoisomerase II in mitotic chromosomes

    OpenAIRE

    1985-01-01

    In the preceding article we described a polyclonal antibody that recognizes cSc-1, a major polypeptide component of the chicken mitotic chromosome scaffold. This polypeptide was shown to be chicken topoisomerase II. In the experiments described in the present article we use indirect immunofluorescence and immunoelectron microscopy to examine the distribution of topoisomerase II within intact chromosomes. We also describe a simple experimental protocol that differentiates antigens that are int...

  2. Female meiotic sex chromosome inactivation in chicken.

    Directory of Open Access Journals (Sweden)

    Sam Schoenmakers

    2009-05-01

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

  3. Abnormal sex chromosome constitution and longitudinal growth

    DEFF Research Database (Denmark)

    Aksglaede, Lise; Skakkebaek, Niels E; Juul, Anders

    2008-01-01

    Growth is a highly complex process regulated by the interaction between sex steroids and the GH IGF-axis. However, other factors such as sex chromosome-related genes play independent roles.......Growth is a highly complex process regulated by the interaction between sex steroids and the GH IGF-axis. However, other factors such as sex chromosome-related genes play independent roles....

  4. 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...

  5. Demasculinization of the Anopheles gambiae X chromosome

    Directory of Open Access Journals (Sweden)

    Magnusson Kalle

    2012-05-01

    Full Text Available Abstract Background In a number of organisms sex-biased genes are non-randomly distributed between autosomes and the shared sex chromosome X (or Z. Studies on Anopheles gambiae have produced conflicting results regarding the underrepresentation of male-biased genes on the X chromosome and it is unclear to what extent sexual antagonism, dosage compensation or X-inactivation in the male germline, the evolutionary forces that have been suggested to affect the chromosomal distribution of sex-biased genes, are operational in Anopheles. Results We performed a meta-analysis of sex-biased gene expression in Anopheles gambiae which provides evidence for a general underrepresentation of male-biased genes on the X-chromosome that increased in significance with the observed degree of sex-bias. A phylogenomic comparison between Drosophila melanogaster, Aedes aegypti and Culex quinquefasciatus also indicates that the Anopheles X chromosome strongly disfavours the evolutionary conservation of male-biased expression and that novel male-biased genes are more likely to arise on autosomes. Finally, we demonstrate experimentally that transgenes situated on the Anopheles gambiae X chromosome are transcriptionally silenced in the male germline. Conclusion The data presented here support the hypothesis that the observed demasculinization of the Anopheles X chromosome is driven by X-chromosome inactivation in the male germline and by sexual antagonism. The demasculinization appears to be the consequence of a loss of male-biased expression, rather than a failure in the establishment or the extinction of male-biased genes.

  6. Delayed chromosomal instability induced by DNA damage.

    OpenAIRE

    Marder, B A; Morgan, W. F.

    1993-01-01

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

  7. Plasmid and chromosome segregation in prokaryotes

    DEFF Research Database (Denmark)

    Møller-Jensen, Jakob; Bugge Jensen, Rasmus; Gerdes, Kenn

    2000-01-01

    Recent major advances in the understanding of prokaryotic DNA segregation have been achieved by using fluorescence microscopy to visualize the localization of cellular components. Plasmids and bacterial chromosomes are partitioned in a highly dynamic fashion, suggesting the presence of a mitotic......-like apparatus in prokaryotes. The identification of chromosomal homologues of the well-characterized plasmid partitioning genes indicates that there could be a general mechanism of bacterial DNA partitioning. Udgivelsesdato: July 1...

  8. Principles of chromosomal organization: lessons from yeast

    OpenAIRE

    Zimmer, Christophe; Fabre, Emmanuelle

    2011-01-01

    The spatial organization of genes and chromosomes plays an important role in the regulation of several DNA processes. However, the principles and forces underlying this nonrandom organization are mostly unknown. Despite its small dimension, and thanks to new imaging and biochemical techniques, studies of the budding yeast nucleus have led to significant insights into chromosome arrangement and dynamics. The dynamic organization of the yeast genome during interphase argues for both the physica...

  9. Bacterial Artificial Chromosome Mutagenesis Using Recombineering

    OpenAIRE

    Kumaran Narayanan; Qingwen Chen

    2011-01-01

    Gene expression from bacterial artificial chromosome (BAC) clones has been demonstrated to facilitate physiologically relevant levels compared to viral and nonviral cDNA vectors. BACs are large enough to transfer intact genes in their native chromosomal setting together with flanking regulatory elements to provide all the signals for correct spatiotemporal gene expression. Until recently, the use of BACs for functional studies has been limited because their large size has inherently presented...

  10. Assembly of Lampbrush Chromosomes from Sperm Chromatin

    OpenAIRE

    Gall, Joseph G.; Murphy, Christine

    1998-01-01

    We have examined the behavior of demembranated sperm heads when injected into the germinal vesicle (GV) of amphibian oocytes. Xenopus sperm heads injected into Xenopus GVs swelled immediately and within hours began to stain with an antibody against RNA polymerase II (Pol II). Over time each sperm head became a loose mass of chromosome-like threads, which by 24–48 h resolved into individually recognizable lampbrush chromosomes (LBCs). Although LBCs derived from sperm are unreplicated single ch...

  11. Sequence conservation on the Y chromosome

    Energy Technology Data Exchange (ETDEWEB)

    Gibson, L.H.; Yang-Feng, L. [Yale Univ. School of Medicine, New Haven, CT (United States); Lau, C. [Univ. of California, San Francisco, CA (United States)

    1994-09-01

    The Y chromosome is present in all mammals and is considered to be essential to sex determination. Despite intense genomic research, only a few genes have been identified and mapped to this chromosome in humans. Several of them, such as SRY and ZFY, have been demonstrated to be conserved and Y-located in other mammals. In order to address the issue of sequence conservation on the Y chromosome, we performed fluorescence in situ hybridization (FISH) with DNA from a human Y cosmid library as a probe to study the Y chromosomes from other mammalian species. Total DNA from 3,000-4,500 cosmid pools were labeled with biotinylated-dUTP and hybridized to metaphase chromosomes. For human and primate preparations, human cot1 DNA was included in the hybridization mixture to suppress the hybridization from repeat sequences. FISH signals were detected on the Y chromosomes of human, gorilla, orangutan and baboon (Old World monkey) and were absent on those of squirrel monkey (New World monkey), Indian munjac, wood lemming, Chinese hamster, rat and mouse. Since sequence analysis suggested that specific genes, e.g. SRY and ZFY, are conserved between these two groups, the lack of detectable hybridization in the latter group implies either that conservation of the human Y sequences is limited to the Y chromosomes of the great apes and Old World monkeys, or that the size of the syntenic segment is too small to be detected under the resolution of FISH, or that homologeous sequences have undergone considerable divergence. Further studies with reduced hybridization stringency are currently being conducted. Our results provide some clues as to Y-sequence conservation across species and demonstrate the limitations of FISH across species with total DNA sequences from a particular chromosome.

  12. Chromosomal profile of indigenous pig (Sus scrofa

    Directory of Open Access Journals (Sweden)

    P. Guru Vishnu

    2015-02-01

    Full Text Available Aim: The objective of this study was to investigate the chromosomal profile of indigenous pigs by computing morphometric measurements. Materials and Methods: A cytogenetic study was carried out in 60 indigenous pigs to analyze the chromosomal profile by employing the short term peripheral blood lymphocyte culture technique. Results: The modal chromosome number (2n in indigenous pigs was found to be 38 and a fundamental number of 64 as in the exotic. First chromosome was the longest pair, and thirteenth pair was the second largest while Y-chromosome was the smallest in the karyotype of the pig. The mean relative length, arm ratio, centromeric indices and morphological indices of chromosomes varied from 1.99±0.01 to 11.23±0.09, 1.04±0.05 to 2.95±0.02, 0.51±0.14 to 0.75±0.09 and 2.08±0.07 to 8.08±0.15%, respectively in indigenous pigs. Sex had no significant effect (p>0.05 on all the morphometric measurements studied. Conclusion: The present study revealed that among autosomes first five pairs were sub metacentric, next two pairs were sub telocentric (6-7, subsequent five pairs were metacentric (8-12 and remaining six pairs were telocentric (13-18, while both allosomes were metacentric. The chromosomal number, morphology and various morphometric measurements of the chromosomes of the indigenous pigs were almost similar to those established breeds reported in the literature.

  13. Die Haplotypisierung des Y-Chromosoms

    OpenAIRE

    Roewer, Lutz

    2001-01-01

    Haploid vererbte Polymorphismen des Y-Chromosoms sind wichtige diagnostische Werkzeuge der forensischen Genetik und verwandter Disziplinen, insbesondere der Anthropologie. Geschlechtsspezifität und uniparentaler Erbgang der Merkmale ermöglichen eine Reihe von Untersuchungen, die mit autosomalen Markern erfolglos bleiben müssen. Kurze tandem-repetitive STR-Sequenzen, die polymorphen Marker der Wahl im forensischen Labor, sind auch auf dem Y-Chromosom nachzuweisen. Aufgrund der rekombinationsfr...

  14. Analysis of Chromosomal Aberrations after Low and High Dose Rate Gamma Irradiation in ATM or NBS Suppressed Human Fibroblast Cells

    Science.gov (United States)

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

    2009-01-01

    A detailed understanding of the biological effects of heavy nuclei is needed for space radiation protection and for cancer therapy. High-LET radiation produces more complex DNA lesions that may be non-repairable or that may require additional processing steps compared to endogenous DSBs, increasing the possibility of misrepair. Interplay between radiation sensitivity, dose, and radiation quality has not been studied extensively. Previously we studied chromosome aberrations induced by low- and high- LET radiation in several cell lines deficient in ATM (ataxia telangactasia mutated; product of the gene that is mutated in ataxia telangiectasia patients) or NBS (nibrin; product of the gene mutated in the Nijmegen breakage syndrome), and gliomablastoma cells that are proficient or lacking in DNA-dependent protein kinase (DNA-PK) activity. We found that the yields of both simple and complex chromosomal aberrations were significantly increased in the DSB repair defective cells compared to normal cells. The increased aberrations observed for the ATM and NBS defective lines was due to a significantly larger quadratic dose-response term compared to normal fibroblasts for both simple and complex aberrations, while the linear dose-response term was significantly higher in NBS cells only for simple exchanges. These results point to the importance of the functions of ATM and NBS in chromatin modifications that function to facilitate correct DSB repair and minimize aberration formation. To further understand the sensitivity differences that were observed in ATM and NBS deficient cells, in this study, chromosomal aberration analysis was performed in normal lung fibroblast cells treated with KU-55933, a specific ATM kinase inhibitor, or Mirin, an MRN complex inhibitor involved in activation of ATM. We are also testing siRNA knockdown of these proteins. Normal and ATM or NBS suppressed cells were irradiated with gamma-rays and chromosomes were collected with a premature chromosome

  15. Aurora kinase inhibitors: a new class of drugs targeting the regulatory mitotic system.

    Science.gov (United States)

    Pérez Fidalgo, José Alejandro; Roda, Desamparados; Roselló, Susana; Rodríguez-Braun, Edith; Cervantes, Andrés

    2009-12-01

    The present review gives a perspective on the Aurora kinase family members, their function in normal cells, their role in cancer progression as well as their potential as target for anticancer treatment. Mitosis has been an important target for anticancer therapy development, leading to some specific drugs mainly addressing Tubulines, as a key structure of the mitotic spindle. Vinca alkaloids, taxanes or epotilones are good examples of conventionally developed antimitotic agents. However, novel classes of antineoplastic drugs are being studied, targeting the regulatory system that controls functional aspects of mitosis, such as Aurora or Polo-like kinases or Kinespondin inhibitors. The specific role of the different Aurora kinase proteins as regulator enzymes of the mitotic process in normal cells is discussed. Some of the mechanisms that link Aurora overexpression with cancer are also considered. Thereafter, the clinical and preclinical development of the different Aurora kinase inhibitors is presented. This is nowadays a very active area of therapeutic research and at least, sixteen new compounds are being studied as potential antineoplastic drugs. Most of them are in a very early phase of clinical development. However, we summarized the most recently published findings related with these drugs: main characteristics, way of administration, dose limiting toxicities and recommended doses for further studies. Another important aspect in Aurora kinase inhibition is the study and validation of potential biomarkers to optimize the clinical development. Several studies included pharmacodynamic assessments in normal blood cells, skin or/and tumor biopsies. Several proposals included a higher mitotic index, a decreased number of mitosis with bipolar spindles or normal alignment of chromosomes and inhibition of histone H3 phosphorylation. Future strategies and challenges for trials with Aurora kinase inhibitors are also discussed. PMID:20045785

  16. The X chromosome of monotremes shares a highly conserved region with the eutherian and marsupial X chromosomes despite the absence of X chromosome inactivation.

    OpenAIRE

    Watson, J M; Spencer, J. A.; Riggs, A D; Graves, J.A.

    1990-01-01

    Eight genes, located on the long arm of the human X chromosome and present on the marsupial X chromosome, were mapped by in situ hybridization to the chromosomes of the platypus Ornithorhynchus anatinus, one of the three species of monotreme mammals. All were located on the X chromosome. We conclude that the long arm of the human X chromosome represents a highly conserved region that formed part of the X chromosome in a mammalian ancestor at least 150 million years ago. Since three of these g...

  17. Characterizing the chromosomes of the platypus (Ornithorhynchus anatinus).

    Science.gov (United States)

    McMillan, Daniel; Miethke, Pat; Alsop, Amber E; Rens, Willem; O'Brien, Patricia; Trifonov, Vladimir; Veyrunes, Frederic; Schatzkamer, Kyriena; Kremitzki, Colin L; Graves, Tina; Warren, Wesley; Grützner, Frank; Ferguson-Smith, Malcolm A; Graves, Jennifer A Marshall

    2007-01-01

    Like the unique platypus itself, the platypus genome is extraordinary because of its complex sex chromosome system, and is controversial because of difficulties in identification of small autosomes and sex chromosomes. A 6-fold shotgun sequence of the platypus genome is now available and is being assembled with the help of physical mapping. It is therefore essential to characterize the chromosomes and resolve the ambiguities and inconsistencies in identifying autosomes and sex chromosomes. We have used chromosome paints and DAPI banding to identify and classify pairs of autosomes and sex chromosomes. We have established an agreed nomenclature and identified anchor BAC clones for each chromosome that will ensure unambiguous gene localizations. PMID:18185982

  18. Chromosomal variations in the primate Alouatta seniculus seniculus.

    Science.gov (United States)

    Yunis, E J; Torres de Caballero, O M; Ramírez, C; Ramírez, Z E

    1976-01-01

    Chromosome analysis in 23 specimens of Alouatta s. seniculus trapped in different localities of Colombia were examined with the C- and Q-banding techniques. The chromosome numbers (2n=44) showed variations from 2n = 43 to 2n = 45 involving three and five microchromosomes, respectively. Two specimens also showed a structural chromosome variation involving a pericentric inversion of the chromosome No. 13. Chromosome measurements revealed an X chromosome with a value significantly smaller to that established for the standard mammalian X chromosome. PMID:817992

  19. Evolutionary stability of sex chromosomes in snakes.

    Science.gov (United States)

    Rovatsos, Michail; Vukić, Jasna; Lymberakis, Petros; Kratochvíl, Lukáš

    2015-12-22

    Amniote vertebrates possess various mechanisms of sex determination, but their variability is not equally distributed. The large evolutionary stability of sex chromosomes in viviparous mammals and birds was believed to be connected with their endothermy. However, some ectotherm lineages seem to be comparably conserved in sex determination, but previously there was a lack of molecular evidence to confirm this. Here, we document a stability of sex chromosomes in advanced snakes based on the testing of Z-specificity of genes using quantitative PCR (qPCR) across 37 snake species (our qPCR technique is suitable for molecular sexing in potentially all advanced snakes). We discovered that at least part of sex chromosomes is homologous across all families of caenophidian snakes (Acrochordidae, Xenodermatidae, Pareatidae, Viperidae, Homalopsidae, Colubridae, Elapidae and Lamprophiidae). The emergence of differentiated sex chromosomes can be dated back to about 60 Ma and preceded the extensive diversification of advanced snakes, the group with more than 3000 species. The Z-specific genes of caenophidian snakes are (pseudo)autosomal in the members of the snake families Pythonidae, Xenopeltidae, Boidae, Erycidae and Sanziniidae, as well as in outgroups with differentiated sex chromosomes such as monitor lizards, iguanas and chameleons. Along with iguanas, advanced snakes are therefore another example of ectothermic amniotes with a long-term stability of sex chromosomes comparable with endotherms. PMID:26702042

  20. Origin and evolution of X chromosome inactivation.

    Science.gov (United States)

    Gribnau, Joost; Grootegoed, J Anton

    2012-06-01

    Evolution of the mammalian sex chromosomes heavily impacts on the expression of X-encoded genes, both in marsupials and placental mammals. The loss of genes from the Y chromosome forced a two-fold upregulation of dose sensitive X-linked homologues. As a corollary, female cells would experience a lethal dose of X-linked genes, if this upregulation was not counteracted by evolution of X chromosome inactivation (XCI) that allows for only one active X chromosome per diploid genome. Marsupials rely on imprinted XCI, which inactivates always the paternally inherited X chromosome. In placental mammals, random XCI (rXCI) is the predominant form, inactivating either the maternal or paternal X. In this review, we discuss recent new insights in the regulation of XCI. Based on these findings, we propose an X inactivation center (Xic), composed of a cis-Xic and trans-Xic that encompass all elements and factors acting to control rXCI either in cis or in trans. We also highlight that XCI may have evolved from a very small nucleation site on the X chromosome in the vicinity of the Sox3 gene. Finally, we discuss the possible evolutionary road maps that resulted in imprinted XCI and rXCI as observed in present day mammals. PMID:22425180

  1. NPM-ALK: The Prototypic Member of a Family of Oncogenic Fusion Tyrosine Kinases

    Directory of Open Access Journals (Sweden)

    Joel D. Pearson

    2012-01-01

    Full Text Available Anaplastic lymphoma kinase (ALK was first identified in 1994 with the discovery that the gene encoding for this kinase was involved in the t(2;5(p23;q35 chromosomal translocation observed in a subset of anaplastic large cell lymphoma (ALCL. The NPM-ALK fusion protein generated by this translocation is a constitutively active tyrosine kinase, and much research has focused on characterizing the signalling pathways and cellular activities this oncoprotein regulates in ALCL. We now know about the existence of nearly 20 distinct ALK translocation partners, and the fusion proteins resulting from these translocations play a critical role in the pathogenesis of a variety of cancers including subsets of large B-cell lymphomas, nonsmall cell lung carcinomas, and inflammatory myofibroblastic tumours. Moreover, the inhibition of ALK has been shown to be an effective treatment strategy in some of these malignancies. In this paper we will highlight malignancies where ALK translocations have been identified and discuss why ALK fusion proteins are constitutively active tyrosine kinases. Finally, using ALCL as an example, we will examine three key signalling pathways activated by NPM-ALK that contribute to proliferation and survival in ALCL.

  2. Raf kinase inhibitory protein: a signal transduction modulator and metastasis suppressor

    Institute of Scientific and Technical Information of China (English)

    Alexey E Granovsky; Marsha Rich Rosner

    2008-01-01

    Cells have a multitude of controls to maintain their integrity and prevent random switching from one biological state to another. Raf Kinase Inhibitory Protein (RKIP), a member of the phosphatidylethanolamine binding protein (PEBP) family, is representative of a new class of modulators of signaling cascades that function to maintain the "yin yang" or balance of biological systems. RKIP inhibits MAP kinase (Raf-MEK-ERK), G protein-coupled receptor (GPCR) kinase and NFkB signaling cascades. Because RKIP targets different kinases dependent upon its state of phosphorylation, RKIP also acts to integrate crosstalk initiated by multiple environmental stimuli. Loss or depletion of RKIP results in disruption of the normal cellular stasis and can lead to chromosomal abnormalities and disease states such as cancer. Since RKIP and the PEBP family have been reviewed previously, the goal of this analysis is to provide an update and highlight some of the unique features of RKIP that make it a critical player in the regulation of cellular signaling processes.

  3. Regulation of the interaction between protein kinase C-related protein kinase 2 (PRK2) and its upstream kinase, 3-phosphoinositide-dependent protein kinase 1 (PDK1)

    DEFF Research Database (Denmark)

    Dettori, Rosalia; Sonzogni, Silvina; Meyer, Lucas;

    2009-01-01

    The members of the AGC kinase family frequently exhibit three conserved phosphorylation sites: the activation loop, the hydrophobic motif (HM), and the zipper (Z)/turn-motif (TM) phosphorylation site. 3-Phosphoinositide-dependent protein kinase 1 (PDK1) phosphorylates the activation loop of...... numerous AGC kinases, including the protein kinase C-related protein kinases (PRKs). Here we studied the docking interaction between PDK1 and PRK2 and analyzed the mechanisms that regulate this interaction. In vivo labeling of recombinant PRK2 by (32)P(i) revealed phosphorylation at two sites, the...... the mechanism that negatively regulates the docking interaction of PRK2 to the upstream kinase PDK1 is directly linked to the activation mechanism of PRK2 itself. Finally, our results indicate that the mechanisms underlying the regulation of the interaction between PRK2 and PDK1 are specific for PRK2...

  4. Localization of ecdysterone on polytene chromosomes of Drosophila melanogaster.

    OpenAIRE

    Gronemeyer, H; Pongs, O

    1980-01-01

    Ecdysterone has been crosslinked in situ to polytene chromosomes of salivary glands of Drosophila melanogaster by photoactivation. The crosslinked hormone has been localized on the chromosomes by indirect immunofluorescence microscopy. At different developmental stages the hormone was detected at different chromosomal loci. These chromosomal sites correspond to ecdysterone-inducible puff sites. Thus, the hormone binds directly to chromosomal loci, whose transcription depends on the presence o...

  5. Diacylglycerol Kinase Inhibition and Vascular Function

    OpenAIRE

    Choi, Hyehun; Allahdadi, Kyan J.; Tostes, Rita C A; Webb, R. Clinton

    2009-01-01

    Diacylglycerol kinases (DGKs), a family of lipid kinases, convert diacylglycerol (DG) to phosphatidic acid (PA). Acting as a second messenger, DG activates protein kinase C (PKC). PA, a signaling lipid, regulates diverse functions involved in physiological responses. Since DGK modulates two lipid second messengers, DG and PA, regulation of DGK could induce related cellular responses. Currently, there are 10 mammalian isoforms of DGK that are categorized into five groups based on their structu...

  6. Chromosomal Aberrations in DNA Repair Defective Cell Lines: Comparisons of Dose Rate and Radiation Quality

    Science.gov (United States)

    George, K. A.; Hada, M.; Patel, Z.; Huff, J.; Pluth, J. M.; Cucinotta, F. A.

    2009-01-01

    Chromosome aberration yields were assessed in DNA double-strand break repair (DSB) deficient cells after acute doses of gamma-rays or high-LET iron nuclei, or low dose-rate (0.018 Gy/hr) gamma-rays. We studied several cell lines including fibroblasts deficient in ATM (product of the gene that is mutated in ataxia telangiectasia patients) or NBS (product of the gene mutated in the Nijmegen breakage syndrome), and gliomablastoma cells that are proficient or lacking in DNA-dependent protein kinase, DNA-PK activity. Chromosomes were analyzed using the fluorescence in-situ hybridization (FISH) chromosome painting method in cells at the first division post-irradiation and chromosome aberrations were identified as either simple exchanges (translocations and dicentrics) or complex exchanges (involving >2 breaks in 2 or more chromosomes). Gamma radiation induced higher yields of both simple and complex exchanges in the DSB repair defective cells than in the normal cells. The quadratic dose-response terms for both chromosome exchange types were significantly higher for the ATM and NBS defective lines than for normal fibroblasts. However, the linear dose-response term was significantly higher only for simple exchanges in the NBS cells. Large increases in the quadratic dose response terms indicate the important roles of ATM and NBS in chromatin modifications that facilitate correct DSB repair and minimize aberration formation. Differences in the response of AT and NBS deficient cells at lower doses suggests important questions about the applicability of observations of radiation sensitivity at high dose to low dose exposures. For all iron nuclei irradiated cells, regression models preferred purely linear and quadratic dose responses for simple and complex exchanges, respectively. All the DNA repair defective cell lines had lower Relative biological effectiveness (RBE) values than normal cells, the lowest being for the DNA-PK-deficient cells, which was near unity. To further

  7. Allosteric small-molecule kinase inhibitors

    DEFF Research Database (Denmark)

    Wu, Peng; Clausen, Mads Hartvig; Nielsen, Thomas E.

    2015-01-01

    Small-molecule kinase inhibitors are invaluable targeted therapeutics for the treatment of various human diseases, especially cancers. While the majority of approved and developed preclinical small-molecule inhibitors are characterized as type I or type II inhibitors that target the ATP......-binding pocket of kinases, the remarkable sequential and structural similarity among ATP pockets renders the selective inhibition of kinases a daunting challenge. Therefore, targeting allosteric pockets of kinases outside the highly conversed ATP pocket has been proposed as a promising alternative to overcome...

  8. MST kinases in development and disease

    OpenAIRE

    Thompson, Barry J.; Sahai, Erik

    2015-01-01

    The mammalian MST kinase family, which is related to the Hippo kinase in Drosophila melanogaster, includes five related proteins: MST1 (also called STK4), MST2 (also called STK3), MST3 (also called STK24), MST4, and YSK1 (also called STK25 or SOK1). MST kinases are emerging as key signaling molecules that influence cell proliferation, organ size, cell migration, and cell polarity. Here we review the regulation and function of these kinases in normal physiology and pathologies, including cance...

  9. Identification and characterization of potential tumor suppressor genes for ovarian cancer on chromosome 8p22

    International Nuclear Information System (INIS)

    Frequent Loss of Heterozygosity (LOH) in specific chromosomal regions of tumors indicates the residence of at least one tumor suppressor gene (TSG) in the corresponding chromosomal region. Chromosome 8p22 is described as LOH hotspot in several epithelial tumors. However, the related genes of this chromosomal band are still very poorly described. The aim of this study was the identification and characterization of potential tumor suppressor genes on chromosome 8p22 in ovarian cancer. Two out of 22 genes of 8p22, hVps37A and TuSC3, turned out to be promising tumor suppressor candidates and were characterized in more detail. It could be shown that hVps37 expression is significantly reduced in primary ovarian tumors relative to normal ovarian epithelials. Furthermore, survival rates of the patients were directly correlated with the hVps37A expression of the corresponding tumors. In-vitro characterization of hVps37A in two ovarian cancer cell lines resulted in an explanatory model of the clinical observations. As part of the ESCRT-I complex hVps37A is involved in the degradation process of activated receptor tyrosine kinases (RTKs) including the well described oncogenes EGFR and HER2. Consequently, hVps37A knockdown led to a hyperactivation of the MAPK (Mitogen Activated Protein Kinase) pathway secondary to accumulating amounts of the activated EGFR (pEGFR) in the cytoplasm. Furthermore, the hVps37-silenced cell lines developed a resistance against the growth inhibitory effect of Cetuximab. In contrast to hVps37A, 29.7% of the tumors analyzed were methylated at the TuSC3 promoter, accompanied with reduced mRNA expression and unfavourable survival rate of the patients. Therefore, promoter methylation turned out to be an independent prognostic factor for ovarian cancer. In-vitro, it could be shown that TuSCS3 resides in the endoplasmatic reticulum and is involved in the N-glycosylation process of integrin-β1 and potentially further proteins. Moreover, reconstitution of

  10. Seeding Collaborations to Advance Kinase Science with the GSK Published Kinase Inhibitor Set (PKIS)

    OpenAIRE

    Drewry, David H.; Willson, Timothy M.; Zuercher, William J

    2014-01-01

    To catalyze research on historically untargeted protein kinases, we created the PKIS, an annotated set of 367 small molecule kinase inhibitors. The set has been widely distributed to academic collaborators as an open access tool. It has been used to identify chemical starting points for development of chemical probes for orphan kinases and to investigate kinase signaling in high content phenotypic assays. Access to the set comes with few restrictions other than the requirement that assay resu...

  11. Investigation of Partamona helleri (Apidae, Meliponini) B chromosome origin. An approach by microdissection and whole chromosome painting

    OpenAIRE

    Martins, Cinthia; Diniz, Debora; Sobrinho-Scudeler, Patricia; Foresti, Fausto; Campos, Lucio; Costa, Marco

    2012-01-01

    The stingless bee Partamona helleri in southeast Brazil shows the regular chromosome number 2n = 34 and a variable number of up to four minute B1 or B2 chromosomes. Previous cytogenetic analyses have indicated morphological similarities between the B1 chromosome and chromosome segments in the regular karyotype. In this study, microdissection and chromosome painting were employed along with C banding, NOR banding, and base-specific fluorochrome staining to investigate the origin of the B1 chro...

  12. The Program of Sex Chromosome Pairing in Meiosis Is Highly Conserved Across Marsupial Species: Implications for Sex Chromosome Evolution

    OpenAIRE

    Page, Jesús; Berríos, Soledad; Parra, María Teresa; Viera, Alberto; Suja, José Ángel; Prieto, Ignacio; Barbero, José Luis; Rufas, Julio S; Fernández-Donoso, Raúl

    2005-01-01

    Marsupials present a series of genetic and chromosomal features that are highly conserved in very distant species. One of these features is the absence of a homologous region between X and Y chromosomes. According to this genetic differentiation, sex chromosomes do not synapse during the first meiotic prophase in males, and a special structure, the dense plate, maintains sex chromosome association. In this report we present results on the process of meiotic sex chromosome pairing obtained fro...

  13. Klinefelter syndrome and other sex chromosomal aneuploidies

    Directory of Open Access Journals (Sweden)

    Graham John M

    2006-10-01

    Full Text Available Abstract The term Klinefelter syndrome (KS describes a group of chromosomal disorder in which there is at least one extra X chromosome to a normal male karyotype, 46,XY. XXY aneuploidy is the most common disorder of sex chromosomes in humans, with prevalence of one in 500 males. Other sex chromosomal aneuploidies have also been described, although they are much less frequent, with 48,XXYY and 48,XXXY being present in 1 per 17,000 to 1 per 50,000 male births. The incidence of 49,XXXXY is 1 per 85,000 to 100,000 male births. In addition, 46,XX males also exist and it is caused by translocation of Y material including sex determining region (SRY to the X chromosome during paternal meiosis. Formal cytogenetic analysis is necessary to make a definite diagnosis, and more obvious differences in physical features tend to be associated with increasing numbers of sex chromosomes. If the diagnosis is not made prenatally, 47,XXY males may present with a variety of subtle clinical signs that are age-related. In infancy, males with 47,XXY may have chromosomal evaluations done for hypospadias, small phallus or cryptorchidism, developmental delay. The school-aged child may present with language delay, learning disabilities, or behavioral problems. The older child or adolescent may be discovered during an endocrine evaluation for delayed or incomplete pubertal development with eunuchoid body habitus, gynecomastia, and small testes. Adults are often evaluated for infertility or breast malignancy. Androgen replacement therapy should begin at puberty, around age 12 years, in increasing dosage sufficient to maintain age appropriate serum concentrations of testosterone, estradiol, follicle stimulating hormone (FSH, and luteinizing hormone (LH. The effects on physical and cognitive development increase with the number of extra Xs, and each extra X is associated with an intelligence quotient (IQ decrease of approximately 15–16 points, with language most affected

  14. Chromosomal organization of adrenergic receptor genes

    International Nuclear Information System (INIS)

    The adrenergic receptors (ARs) (subtypes α1, α2, β1, and β2) are a prototypic family of guanine nucleotide binding regulatory protein-coupled receptors that mediate the physiological effects of the hormone epinephrine and the neurotransmitter norepinephrine. The authors have previously assigned the genes for β2-and α2-AR to human chromosomes 5 and 10, respectively. By Southern analysis of somatic cell hybrids and in situ chromosomal hybridization, they have now mapped the α1-AR gene to chromosome 5q32→q34, the same position as β2-AR, and the β1-AR gene to chromosome 10q24→q26, the region where α2-AR, is located. In mouse, both α2-and β1-AR genes were assigned to chromosome 19, and the α1-AR locus was localized to chromosome 11. Pulsed field gel electrophoresis has shown that the α1-and β2-AR genes in humans are within 300 kilobases (kb) and the distance between the α2- and β1-AR genes is <225 kb. The proximity of these two pairs of AR genes and the sequence similarity that exists among all the ARs strongly suggest that they are evolutionarily related. Moreover, they likely arose from a common ancestral receptor gene and subsequently diverged through gene duplication and chromosomal duplication to perform their distinctive roles in mediation the physiological effects of catecholamines. The AR genes thus provide a paradigm for understanding the evolution of such structurally conserved yet functionally divergent families off receptor molecules

  15. Molecular mapping of chromosomes 17 and X

    Energy Technology Data Exchange (ETDEWEB)

    Barker, D.F.

    1991-01-15

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

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

    International Nuclear Information System (INIS)

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

  17. Chromosome and genome size variation in Luzula (Juncaceae), a genus with holocentric chromosomes

    Czech Academy of Sciences Publication Activity Database

    Bozek, M.; Leitch, A. R.; Leitch, I. J.; Záveská Drábková, Lenka; Kuta, E.

    2012-01-01

    Roč. 170, č. 4 (2012), s. 529-541. ISSN 0024-4074 R&D Projects: GA ČR GP206/07/P147 Institutional support: RVO:67985939 Keywords : chromosomal evolution * endopolyploidy * holokinetic chromosome * karyotype evolution * tetraploides * centromeres * TRNF intergenic spacer Subject RIV: EF - Botanics Impact factor: 2.589, year: 2012

  18. Sequencing papaya X and Yh chromosomes reveals molecular basis of incipient sex chromosome evolution.

    Science.gov (United States)

    Wang, Jianping; Na, Jong-Kuk; Yu, Qingyi; Gschwend, Andrea R; Han, Jennifer; Zeng, Fanchang; Aryal, Rishi; VanBuren, Robert; Murray, Jan E; Zhang, Wenli; Navajas-Pérez, Rafael; Feltus, F Alex; Lemke, Cornelia; Tong, Eric J; Chen, Cuixia; Wai, Ching Man; Singh, Ratnesh; Wang, Ming-Li; Min, Xiang Jia; Alam, Maqsudul; Charlesworth, Deborah; Moore, Paul H; Jiang, Jiming; Paterson, Andrew H; Ming, Ray

    2012-08-21

    Sex determination in papaya is controlled by a recently evolved XY chromosome pair, with two slightly different Y chromosomes controlling the development of males (Y) and hermaphrodites (Y(h)). To study the events of early sex chromosome evolution, we sequenced the hermaphrodite-specific region of the Y(h) chromosome (HSY) and its X counterpart, yielding an 8.1-megabase (Mb) HSY pseudomolecule, and a 3.5-Mb sequence for the corresponding X region. The HSY is larger than the X region, mostly due to retrotransposon insertions. The papaya HSY differs from the X region by two large-scale inversions, the first of which likely caused the recombination suppression between the X and Y(h) chromosomes, followed by numerous additional chromosomal rearrangements. Altogether, including the X and/or HSY regions, 124 transcription units were annotated, including 50 functional pairs present in both the X and HSY. Ten HSY genes had functional homologs elsewhere in the papaya autosomal regions, suggesting movement of genes onto the HSY, whereas the X region had none. Sequence divergence between 70 transcripts shared by the X and HSY revealed two evolutionary strata in the X chromosome, corresponding to the two inversions on the HSY, the older of which evolved about 7.0 million years ago. Gene content differences between the HSY and X are greatest in the older stratum, whereas the gene content and order of the collinear regions are identical. Our findings support theoretical models of early sex chromosome evolution. PMID:22869747

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

    International Nuclear Information System (INIS)

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

  20. Sensitive kinase assay linked with phosphoproteomics for identifying direct kinase substrates.

    Science.gov (United States)

    Xue, Liang; Wang, Wen-Horng; Iliuk, Anton; Hu, Lianghai; Galan, Jacob A; Yu, Shuai; Hans, Michael; Geahlen, Robert L; Tao, W Andy

    2012-04-10

    Our understanding of the molecular control of many disease pathologies requires the identification of direct substrates targeted by specific protein kinases. Here we describe an integrated proteomic strategy, termed kinase assay linked with phosphoproteomics, which combines a sensitive kinase reaction with endogenous kinase-dependent phosphoproteomics to identify direct substrates of protein kinases. The unique in vitro kinase reaction is carried out in a highly efficient manner using a pool of peptides derived directly from cellular kinase substrates and then dephosphorylated as substrate candidates. The resulting newly phosphorylated peptides are then isolated and identified by mass spectrometry. A further comparison of these in vitro phosphorylated peptides with phosphopeptides derived from endogenous proteins isolated from cells in which the kinase is either active or inhibited reveals new candidate protein substrates. The kinase assay linked with phosphoproteomics strategy was applied to identify unique substrates of spleen tyrosine kinase (Syk), a protein-tyrosine kinase with duel properties of an oncogene and a tumor suppressor in distinctive cell types. We identified 64 and 23 direct substrates of Syk specific to B cells and breast cancer cells, respectively. Both known and unique substrates, including multiple centrosomal substrates for Syk, were identified, supporting a unique mechanism that Syk negatively affects cell division through its centrosomal kinase activity. PMID:22451900

  1. Comparison of Peptide Array Substrate Phosphorylation of c-Raf and Mitogen Activated Protein Kinase Kinase Kinase 8

    NARCIS (Netherlands)

    Parikh, Kaushal; Diks, Sander H.; Tuynman, Jurriaan H. B.; Verhaar, Auke; Lowenberg, Mark; Hommes, Daan W.; Joore, Jos; Pandey, Akhilesh; Peppelenbosch, Maikel P.

    2009-01-01

    Kinases are pivotal regulators of cellular physiology. The human genome contains more than 500 putative kinases, which exert their action via the phosphorylation of specific substrates. The determinants of this specificity are still only partly understood and as a consequence it is difficult to pred

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

    DEFF Research Database (Denmark)

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

    1992-01-01

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

  3. Dielectrophoretic manipulation of human chromosomes in microfluidic channels: extracting chromosome dielectric properties

    DEFF Research Database (Denmark)

    Clausen, Casper Hyttel; Dimaki, Maria; Buckley, Sonia; Svendsen, Winnie Edith

    2011-01-01

    An investigation of the dielectric properties of polyamine buffer prepared human chromosomes is presented in this paper. Chromosomes prepared in this buffer are only a few micrometers in size and shaped roughly like spherical discs. Dielectrophoresis was therefore chosen as the method of manipula......An investigation of the dielectric properties of polyamine buffer prepared human chromosomes is presented in this paper. Chromosomes prepared in this buffer are only a few micrometers in size and shaped roughly like spherical discs. Dielectrophoresis was therefore chosen as the method of...... manipulation combined with a custom designed microfluidic system containing the required electrodes for dielectrophoresis experiments. Our results show that although this system is presently not able to distinguish between the different chromosomes, it can provide average data for the dielectric properties of...

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

    DEFF Research Database (Denmark)

    Zhou, Qi; Wang, Jun; Huang, Ling; Nie, Wenhui; Wang, Jinhuan; Liu, Yan; Zhao, Xiangyi; Yang, Fengtang; Wang, Wen

    2008-01-01

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

  5. Sex Chromosome Evolution in Amniotes: Applications for Bacterial Artificial Chromosome Libraries

    Science.gov (United States)

    Janes, Daniel E.; Valenzuela, Nicole; Ezaz, Tariq; Amemiya, Chris; Edwards, Scott V.

    2011-01-01

    Variability among sex chromosome pairs in amniotes denotes a dynamic history. Since amniotes diverged from a common ancestor, their sex chromosome pairs and, more broadly, sex-determining mechanisms have changed reversibly and frequently. These changes have been studied and characterized through the use of many tools and experimental approaches but perhaps most effectively through applications for bacterial artificial chromosome (BAC) libraries. Individual BAC clones carry 100–200 kb of sequence from one individual of a target species that can be isolated by screening, mapped onto karyotypes, and sequenced. With these techniques, researchers have identified differences and similarities in sex chromosome content and organization across amniotes and have addressed hypotheses regarding the frequency and direction of past changes. Here, we review studies of sex chromosome evolution in amniotes and the ways in which the field of research has been affected by the advent of BAC libraries. PMID:20981143

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

    International Nuclear Information System (INIS)

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

  7. Plant sex chromosomes: molecular structure and function.

    Science.gov (United States)

    Jamilena, M; Mariotti, B; Manzano, S

    2008-01-01

    Recent molecular and genomic studies carried out in a number of model dioecious plant species, including Asparagus officinalis, Carica papaya, Silene latifolia, Rumex acetosa and Marchantia polymorpha, have shed light on the molecular structure of both homomorphic and heteromorphic sex chromosomes, and also on the gene functions they have maintained since their evolution from a pair of autosomes. The molecular structure of sex chromosomes in species from different plant families represents the evolutionary pathway followed by sex chromosomes during their evolution. The degree of Y chromosome degeneration that accompanies the suppression of recombination between the Xs and Ys differs among species. The primitive Ys of A. officinalis and C. papaya have only diverged from their homomorphic Xs in a short male-specific and non-recombining region (MSY), while the heteromorphic Ys of S. latifolia, R. acetosa and M. polymorpha have diverged from their respective Xs. As in the Y chromosomes of mammals and Drosophila, the accumulation of repetitive DNA, including both transposable elements and satellite DNA, has played an important role in the divergence and size enlargement of plant Ys, and consequently in reducing gene density. Nevertheless, the degeneration process in plants does not appear to have reached the Y-linked genes. Although a low gene density has been found in the sequenced Y chromosome of M. polymorpha, most of its genes are essential and are expressed in the vegetative and reproductive organs in both male and females. Similarly, most of the Y-linked genes that have been isolated and characterized up to now in S. latifolia are housekeeping genes that have X-linked homologues, and are therefore expressed in both males and females. Only one of them seems to be degenerate with respect to its homologous region in the X. Sequence analysis of larger regions in the homomorphic X and Y chromosomes of papaya and asparagus, and also in the heteromorphic sex chromosomes

  8. Differential genetic interactions between Sgs1, DNA-damage checkpoint components and DNA repair factors in the maintenance of chromosome stability

    Directory of Open Access Journals (Sweden)

    Doerfler Lillian

    2011-10-01

    Full Text Available Abstract Background Genome instability is associated with human cancers and chromosome breakage syndromes, including Bloom's syndrome, caused by inactivation of BLM helicase. Numerous mutations that lead to genome instability are known, yet how they interact genetically is poorly understood. Results We show that spontaneous translocations that arise by nonallelic homologous recombination in DNA-damage-checkpoint-defective yeast lacking the BLM-related Sgs1 helicase (sgs1Δ mec3Δ are inhibited if cells lack Mec1/ATR kinase. Tel1/ATM, in contrast, acts as a suppressor independently of Mec3 and Sgs1. Translocations are also inhibited in cells lacking Dun1 kinase, but not in cells defective in a parallel checkpoint branch defined by Chk1 kinase. While we had previously shown that RAD51 deletion did not inhibit translocation formation, RAD59 deletion led to inhibition comparable to the rad52Δ mutation. A candidate screen of other DNA metabolic factors identified Exo1 as a strong suppressor of chromosomal rearrangements in the sgs1Δ mutant, becoming even more important for chromosomal stability upon MEC3 deletion. We determined that the C-terminal third of Exo1, harboring mismatch repair protein binding sites and phosphorylation sites, is dispensable for Exo1's roles in chromosomal rearrangement suppression, mutation avoidance and resistance to DNA-damaging agents. Conclusions Our findings suggest that translocations between related genes can form by Rad59-dependent, Rad51-independent homologous recombination, which is independently suppressed by Sgs1, Tel1, Mec3 and Exo1 but promoted by Dun1 and the telomerase-inhibitor Mec1. We propose a model for the functional interaction between mitotic recombination and the DNA-damage checkpoint in the suppression of chromosomal rearrangements in sgs1Δ cells.

  9. Deficit of mitonuclear genes on the human X chromosome predates sex chromosome formation.

    Science.gov (United States)

    Dean, Rebecca; Zimmer, Fabian; Mank, Judith E

    2015-02-01

    Two taxa studied to date, the therian mammals and Caenorhabditis elegans, display underrepresentations of mitonuclear genes (mt-N genes, nuclear genes whose products are imported to and act within the mitochondria) on their X chromosomes. This pattern has been interpreted as the result of sexual conflict driving mt-N genes off of the X chromosome. However, studies in several other species have failed to detect a convergent biased distribution of sex-linked mt-N genes, leading to questions over the generality of the role of sexual conflict in shaping the distribution of mt-N genes. Here we tested whether mt-N genes moved off of the therian X chromosome following sex chromosome formation, consistent with the role of sexual conflict, or whether the paucity of mt-N genes on the therian X is a chance result of an underrepresentation on the ancestral regions that formed the X chromosome. We used a synteny-based approach to identify the ancestral regions in the platypus and chicken genomes that later formed the therian X chromosome. We then quantified the movement of mt-N genes on and off of the X chromosome and the distribution of mt-N genes on the human X and ancestral X regions. We failed to find an excess of mt-N gene movement off of the X. The bias of mt-N genes on ancestral therian X chromosomes was also not significantly different from the biases on the human X. Together our results suggest that, rather than conflict driving mt-N genes off of the mammalian X, random biases on chromosomes that formed the X chromosome could explain the paucity of mt-N genes in the therian lineage. PMID:25637223

  10. Confirmation of the synteny between human chromosome 22 and mouse chromosome 11

    Energy Technology Data Exchange (ETDEWEB)

    Claudio, J.O.; Rouleau, G.A.; Malo, D. [McGill Univ., Quebec (Canada)

    1994-09-01

    Comparative mapping based on the existence of conserved synteny between human and mouse chromosomes is a useful strategy in determining the chromosomal location of a gene. Using recombinant inbred (RI) strains of mice derived from AKR/J and DBA/2J cross (AKXD), we confirmed the existence of a small area of synteny between the chromosome 22 segment carrying the gene for neurofibromatosis type 2 (NF2) and the most proximal region of mouse chromosome 11 containing its homologue (Nf2). By analyzing the allele distribution pattern of 24 AKXD RI mice using a novel polymorphic dinucleotide (CT){sub n} repeat (D11Mcg1) in the 3{prime} untranslated region of the mouse Nf2 gene and PCR-based simple sequence repeat markers (Research Genetics), we established the chromosomal position of Nf23 on mouse chromosome 11. Minimizing the number of double recombinants in the RI strains analyzed suggests tight linkage of Nf2 to D11Mit1 and D11Mit72 which map to a region containing the genes for leukemia inhibitory factor (Lif) and neurofilament heavy chain polypeptide (Nfh). This region is syntenic to the segment carrying the genes LIF, NF2 and NEFH on human chromosome 22q. We show that D11Mcg1 will be useful for mapping of genes and closely linked loci on the proximal region of mouse chromosome 11. Our data demonstrate the predictive value of comparative mapping and confirm that human chromosome 22q12 is syntenic to the most proximal region of mouse chromosome 11.

  11. Activation of the nimA protein kinase plays a unique role during mitosis that cannot be bypassed by absence of the bimE checkpoint.

    OpenAIRE

    Osmani, A H; O'Donnell, K; Pu, R T; Osmani, S A

    1991-01-01

    Mutation of nimA reversibly arrests cells in late G2 and nimA overexpression promotes premature mitosis. Here we demonstrate that the product of nimA (designated NIMA) has protein kinase activity that can phosphorylate beta-casein but not histone proteins. NIMA kinase activity is cell cycle regulated being 20-fold higher at mitosis when compared to S-phase arrested cells. NIMA activation is normally required in G2 to initiate chromosome condensation, to nucleate spindle pole body microtubules...

  12. Effects of inhibitors of protein kinase C and NO-synthase on the radiation-induced cytogenetic adaptive response in Chinese hamster cells in culture

    International Nuclear Information System (INIS)

    The effect of the serine-threonin kinase inhibitor - staurosporine and inhibitor of NO-synthase - L-NAME on the radiation-induced adaptive response were studied in fibroblasts of Chinese hamster in culture. It is shown that staurosporine and L-NAME inhibit cytogenetic adaptive response induced by β-particles in low doses. Inhibition is not connected with radiosensitizing effect of these agents. L-NAME decreases significantly the γ-rays-induced chromosome aberration yield also. Study confirms the role of protein kinase C in induction of the adaptive response and participation of NO-synthase in this process is noticed for the first time

  13. Chromosome misalignments induce spindle-positioning defects.

    Science.gov (United States)

    Tame, Mihoko A; Raaijmakers, Jonne A; Afanasyev, Pavel; Medema, René H

    2016-03-01

    Cortical pulling forces on astral microtubules are essential to position the spindle. These forces are generated by cortical dynein, a minus-end directed motor. Previously, another dynein regulator termed Spindly was proposed to regulate dynein-dependent spindle positioning. However, the mechanism of how Spindly regulates spindle positioning has remained elusive. Here, we find that the misalignment of chromosomes caused by Spindly depletion is directly provoking spindle misorientation. Chromosome misalignments induced by CLIP-170 or CENP-E depletion or by noscapine treatment are similarly accompanied by severe spindle-positioning defects. We find that cortical LGN is actively displaced from the cortex when misaligned chromosomes are in close proximity. Preventing the KT recruitment of Plk1 by the depletion of PBIP1 rescues cortical LGN enrichment near misaligned chromosomes and re-establishes proper spindle orientation. Hence, KT-enriched Plk1 is responsible for the negative regulation of cortical LGN localization. In summary, we uncovered a compelling molecular link between chromosome alignment and spindle orientation defects, both of which are implicated in tumorigenesis. PMID:26882550

  14. Ambiguous genitalia: a clinical and chromosomal study

    Directory of Open Access Journals (Sweden)

    V. Anantha Kumari

    2015-12-01

    Methods: The study is undertaken with forty cases with ages ranging from new borne to 20 yrs. Out of these 40 cases eight cases are below one year. In these cases physical examination is correlated with ultrasonography and chromosomal analysis. Results: In chromosomal analysis three persons out of forty cases were mosaics with 45, XO/46, twenty one cases who showed the chromosomal pattern as 46, XY mostly showed with no mullarian reminents. On examination palpable gonads were found in labio-scrotal sacs in seventeen cases. One of these cases was reared as girl found cytogenetically as 46, XY with the ultrasonographic impression as small uterus with no ovaries. Nineteen cases who with ambiguous genitalia showed the chromosomal pattern as 46, XX one out of these cases showed enlargement of the breast, and on examination of external genitalia found enlarged clitoris with labiamajora and minora. The child was brought up as male. Genitogram showed the absence of uterus. Conclusions: Chromosomal studies with ultrasonography can help in rearing a child male or female in young generation by surgical and Hormonal therapy. This prevents many problems in later life. This fact should be advertised openly in the public so that illiterate people should be alert. [Int J Res Med Sci 2015; 3(12.000: 3743-3748

  15. Deep Roots for Aboriginal Australian Y Chromosomes.

    Science.gov (United States)

    Bergström, Anders; Nagle, Nano; Chen, Yuan; McCarthy, Shane; Pollard, Martin O; Ayub, Qasim; Wilcox, Stephen; Wilcox, Leah; van Oorschot, Roland A H; McAllister, Peter; Williams, Lesley; Xue, Yali; Mitchell, R John; Tyler-Smith, Chris

    2016-03-21

    Australia was one of the earliest regions outside Africa to be colonized by fully modern humans, with archaeological evidence for human presence by 47,000 years ago (47 kya) widely accepted [1, 2]. However, the extent of subsequent human entry before the European colonial age is less clear. The dingo reached Australia about 4 kya, indirectly implying human contact, which some have linked to changes in language and stone tool technology to suggest substantial cultural changes at the same time [3]. Genetic data of two kinds have been proposed to support gene flow from the Indian subcontinent to Australia at this time, as well: first, signs of South Asian admixture in Aboriginal Australian genomes have been reported on the basis of genome-wide SNP data [4]; and second, a Y chromosome lineage designated haplogroup C(∗), present in both India and Australia, was estimated to have a most recent common ancestor around 5 kya and to have entered Australia from India [5]. Here, we sequence 13 Aboriginal Australian Y chromosomes to re-investigate their divergence times from Y chromosomes in other continents, including a comparison of Aboriginal Australian and South Asian haplogroup C chromosomes. We find divergence times dating back to ∼50 kya, thus excluding the Y chromosome as providing evidence for recent gene flow from India into Australia. PMID:26923783

  16. Assembly and disassembly of mammalian chromosome pellicle

    Institute of Scientific and Technical Information of China (English)

    NIZUMEI; JELITTLE; 等

    1992-01-01

    By means of indirect double immunofluorescent staining,the coordination of PI antigen and perichromonucleolin(PCN),the constituent of nuclear periphery and nucleolus respectively,in the assembly and disassembly of chromosome pellicle during mitosis was studied.It was found that in 3T3 cells,during mitosis PI antigen began to coat the condensing chromosome surface earlier than PCN did.However,both of them completed their coating on chromosome at approximately the same stage of mitosis,prometaphase metaphase,The dissociation of mitosis,Prometaphase metaphase.The dissociation of PI antigen from chromosome pellicle to participate the formation of nuclear periphery took place also ahead of that of PCN,At early telophase PI antigen had been extensively involved in the formation of nuclear periphery,while PCN remained in association with the surface of decondensing chromosomes.At late telophase,when PI antigen was localized in an fairly well formed nuclear periphery,PCN was in a stage of forming prenucleolar bodies.

  17. Chromosome-specific DNA Repeat Probes

    Energy Technology Data Exchange (ETDEWEB)

    Baumgartner, Adolf; Weier, Jingly Fung; Weier, Heinz-Ulrich G.

    2006-03-16

    In research as well as in clinical applications, fluorescence in situ hybridization (FISH) has gained increasing popularity as a highly sensitive technique to study cytogenetic changes. Today, hundreds of commercially available DNA probes serve the basic needs of the biomedical research community. Widespread applications, however, are often limited by the lack of appropriately labeled, specific nucleic acid probes. We describe two approaches for an expeditious preparation of chromosome-specific DNAs and the subsequent probe labeling with reporter molecules of choice. The described techniques allow the preparation of highly specific DNA repeat probes suitable for enumeration of chromosomes in interphase cell nuclei or tissue sections. In addition, there is no need for chromosome enrichment by flow cytometry and sorting or molecular cloning. Our PCR-based method uses either bacterial artificial chromosomes or human genomic DNA as templates with {alpha}-satellite-specific primers. Here we demonstrate the production of fluorochrome-labeled DNA repeat probes specific for human chromosomes 17 and 18 in just a few days without the need for highly specialized equipment and without the limitation to only a few fluorochrome labels.

  18. Deep Roots for Aboriginal Australian Y Chromosomes

    Science.gov (United States)

    Bergström, Anders; Nagle, Nano; Chen, Yuan; McCarthy, Shane; Pollard, Martin O.; Ayub, Qasim; Wilcox, Stephen; Wilcox, Leah; van Oorschot, Roland A.H.; McAllister, Peter; Williams, Lesley; Xue, Yali; Mitchell, R. John; Tyler-Smith, Chris

    2016-01-01

    Summary Australia was one of the earliest regions outside Africa to be colonized by fully modern humans, with archaeological evidence for human presence by 47,000 years ago (47 kya) widely accepted [1, 2]. However, the extent of subsequent human entry before the European colonial age is less clear. The dingo reached Australia about 4 kya, indirectly implying human contact, which some have linked to changes in language and stone tool technology to suggest substantial cultural changes at the same time [3]. Genetic data of two kinds have been proposed to support gene flow from the Indian subcontinent to Australia at this time, as well: first, signs of South Asian admixture in Aboriginal Australian genomes have been reported on the basis of genome-wide SNP data [4]; and second, a Y chromosome lineage designated haplogroup C∗, present in both India and Australia, was estimated to have a most recent common ancestor around 5 kya and to have entered Australia from India [5]. Here, we sequence 13 Aboriginal Australian Y chromosomes to re-investigate their divergence times from Y chromosomes in other continents, including a comparison of Aboriginal Australian and South Asian haplogroup C chromosomes. We find divergence times dating back to ∼50 kya, thus excluding the Y chromosome as providing evidence for recent gene flow from India into Australia. PMID:26923783

  19. 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

  20. Degeneration of the Y chromosome in evolutionary aging models

    Science.gov (United States)

    Lobo, M. P.; Onody, R. N.

    2005-06-01

    The Y chromosomes are genetically degenerated and do not recombine with their matching partners X. Recombination of XX pairs is pointed out as the key factor for the Y chromosome degeneration. However, there is an additional evolutionary force driving sex-chromosomes evolution. Here we show this mechanism by means of two different evolutionary models, in which sex chromosomes with non-recombining XX and XY pairs of chromosomes is considered. Our results show three curious effects. First, we observed that even when both XX and XY pairs of chromosomes do not recombine, the Y chromosomes still degenerate. Second, the accumulation of mutations on Y chromosomes followed a completely different pattern then those accumulated on X chromosomes. And third, the models may differ with respect to sexual proportion. These findings suggest that a more primeval mechanism rules the evolution of Y chromosomes due exclusively to the sex-chromosomes asymmetry itself, i.e., the fact that Y chromosomes never experience female bodies. Over aeons, natural selection favored X chromosomes spontaneously, even if at the very beginning of evolution, both XX and XY pairs of chromosomes did not recombine.

  1. Genetics Home Reference: pyruvate kinase deficiency

    Science.gov (United States)

    ... National (UK) Information Centre for Metabolic Diseases National Organization for Rare Disorders (NORD): Pyruvate Kinase Deficiency Genetic Testing Registry (1 link) Pyruvate kinase deficiency of red cells Scientific articles on PubMed (1 link) PubMed OMIM (1 link) ...

  2. A multisubstrate deoxyribonucleoside kinase from plants

    DEFF Research Database (Denmark)

    Clausen, Anders R.; Girandon, Lenart; Knecht, Wolfgang;

    2008-01-01

    Deoxyribonucleoside kinases catalyze the rate limiting step during the salvage of deoxyribonucleosides and convert them into the corresponding monophosphate compounds. We have identified and characterized a unique multisubstrate deoxyribonucleoside kinase from plants. The phylogenetic relationship...... suicide gene in anti-cancer therapy....

  3. The complete sequence of human chromosome 5

    Energy Technology Data Exchange (ETDEWEB)

    Schmutz, Jeremy; Martin, Joel; Terry, Astrid; Couronne, Olivier; Grimwood, Jane; Lowry, State; Gordon, Laurie A.; Scott, Duncan; Xie, Gary; Huang, Wayne; Hellsten, Uffe; Tran-Gyamfi, Mary; She, Xinwei; Prabhakar, Shyam; Aerts, Andrea; Altherr, Michael; Bajorek, Eva; Black, Stacey; Branscomb, Elbert; Caoile, Chenier; Challacombe, Jean F.; Chan, Yee Man; Denys, Mirian; Detter, Chris; Escobar, Julio; Flowers, Dave; Fotopulos, Dea; Glavina, Tijana; Gomez, Maria; Gonzales, Eidelyn; Goodstenin, David; Grigoriev, Igor; Groza, Matthew; Hammon, Nancy; Hawkins, Trevor; Haydu, Lauren; Israni, Sanjay; Jett, Jamie; Kadner, Kristen; Kimbal, Heather; Kobayashi, Arthur; Lopez, Frederick; Lou, Yunian; Martinez, Diego; Medina, Catherine; Morgan, Jenna; Nandkeshwar, Richard; Noonan, James P.; Pitluck, Sam; Pollard, Martin; Predki, Paul; Priest, James; Ramirez, Lucia; Rash, Sam; Retterer, James; Rodriguez, Alex; Rogers, Stephanie; Salamov, Asaf; Salazar, Angelica; Thayer, Nina; Tice, Hope; Tsai, Ming; Ustaszewska, Anna; Vo, Nu; Wheeler, Jeremy; Wu, Kevin; Yang, Joan; Dickson, Mark; Cheng, Jan-Fang; Eichler, Evan E.; Olsen, Anne; Pennacchio, Len A.; Rokhsar, Daniel S.; Richardson, Paul; Lucas, Susan M.; Myers, Richard M.; Rubin, Edward M.

    2004-04-15

    Chromosome 5 is one of the largest human chromosomes yet has one of the lowest gene densities. This is partially explained by numerous gene-poor regions that display a remarkable degree of noncoding and syntenic conservation with non-mammalian vertebrates, suggesting they are functionally constrained. In total, we compiled 177.7 million base pairs of highly accurate finished sequence containing 923 manually curated protein-encoding genes including the protocadherin and interleukin gene families and the first complete versions of each of the large chromosome 5 specific internal duplications. These duplications are very recent evolutionary events and play a likely mechanistic role, since deletions of these regions are the cause of debilitating disorders including spinal muscular atrophy (SMA).

  4. Chromosomal abnormalities in a psychiatric population

    Energy Technology Data Exchange (ETDEWEB)

    Lewis, K.E.; Lubetsky, M.J.; Wenger, S.L.; Steele, M.W. [Univ. of Pittsburgh Medical Center, PA (United States)

    1995-02-27

    Over a 3.5 year period of time, 345 patients hospitalized for psychiatric problems were evaluated cytogenetically. The patient population included 76% males and 94% children with a mean age of 12 years. The criteria for testing was an undiagnosed etiology for mental retardation and/or autism. Cytogenetic studies identified 11, or 3%, with abnormal karyotypes, including 4 fragile X positive individuals (2 males, 2 females), and 8 with chromosomal aneuploidy, rearrangements, or deletions. While individuals with chromosomal abnormalities do not demonstrate specific behavioral, psychiatric, or developmental problems relative to other psychiatric patients, our results demonstrate the need for an increased awareness to order chromosomal analysis and fragile X testing in those individuals who have combinations of behavioral/psychiatric, learning, communication, or cognitive disturbance. 5 refs., 1 fig., 2 tabs.

  5. Plasmid and chromosome partitioning: surprises from phylogeny

    DEFF Research Database (Denmark)

    Gerdes, Kenn; Møller-Jensen, Jakob; Bugge Jensen, Rasmus

    2000-01-01

    Plasmids encode partitioning genes (par) that are required for faithful plasmid segregation at cell division. Initially, par loci were identified on plasmids, but more recently they were also found on bacterial chromosomes. We present here a phylogenetic analysis of par loci from plasmids...... and chromosomes from prokaryotic organisms. All known plasmid-encoded par loci specify three components: a cis-acting centromere-like site and two trans-acting proteins that form a nucleoprotein complex at the centromere (i.e. the partition complex). The proteins are encoded by two genes in an operon...... that is autoregulated by the par-encoded proteins. In all cases, the upstream gene encodes an ATPase that is essential for partitioning. Recent cytological analyses indicate that the ATPases function as adaptors between a host-encoded component and the partition complex and thereby tether plasmids and chromosomal...

  6. The DNA sequence of human chromosome 7.

    Science.gov (United States)

    Hillier, Ladeana W; Fulton, Robert S; Fulton, Lucinda A; Graves, Tina A; Pepin, Kymberlie H; Wagner-McPherson, Caryn; Layman, Dan; Maas, Jason; Jaeger, Sara; Walker, Rebecca; Wylie, Kristine; Sekhon, Mandeep; Becker, Michael C; O'Laughlin, Michelle D; Schaller, Mark E; Fewell, Ginger A; Delehaunty, Kimberly D; Miner, Tracie L; Nash, William E; Cordes, Matt; Du, Hui; Sun, Hui; Edwards, Jennifer; Bradshaw-Cordum, Holland; Ali, Johar; Andrews, Stephanie; Isak, Amber; Vanbrunt, Andrew; Nguyen, Christine; Du, Feiyu; Lamar, Betty; Courtney, Laura; Kalicki, Joelle; Ozersky, Philip; Bielicki, Lauren; Scott, Kelsi; Holmes, Andrea; Harkins, Richard; Harris, Anthony; Strong, Cynthia Madsen; Hou, Shunfang; Tomlinson, Chad; Dauphin-Kohlberg, Sara; Kozlowicz-Reilly, Amy; Leonard, Shawn; Rohlfing, Theresa; Rock, Susan M; Tin-Wollam, Aye-Mon; Abbott, Amanda; Minx, Patrick; Maupin, Rachel; Strowmatt, Catrina; Latreille, Phil; Miller, Nancy; Johnson, Doug; Murray, Jennifer; Woessner, Jeffrey P; Wendl, Michael C; Yang, Shiaw-Pyng; Schultz, Brian R; Wallis, John W; Spieth, John; Bieri, Tamberlyn A; Nelson, Joanne O; Berkowicz, Nicolas; Wohldmann, Patricia E; Cook, Lisa L; Hickenbotham, Matthew T; Eldred, James; Williams, Donald; Bedell, Joseph A; Mardis, Elaine R; Clifton, Sandra W; Chissoe, Stephanie L; Marra, Marco A; Raymond, Christopher; Haugen, Eric; Gillett, Will; Zhou, Yang; James, Rose; Phelps, Karen; Iadanoto, Shawn; Bubb, Kerry; Simms, Elizabeth; Levy, Ruth; Clendenning, James; Kaul, Rajinder; Kent, W James; Furey, Terrence S; Baertsch, Robert A; Brent, Michael R; Keibler, Evan; Flicek, Paul; Bork, Peer; Suyama, Mikita; Bailey, Jeffrey A; Portnoy, Matthew E; Torrents, David; Chinwalla, Asif T; Gish, Warren R; Eddy, Sean R; McPherson, John D; Olson, Maynard V; Eichler, Evan E; Green, Eric D; Waterston, Robert H; Wilson, Richard K

    2003-07-10

    Human chromosome 7 has historically received prominent attention in the human genetics community, primarily related to the search for the cystic fibrosis gene and the frequent cytogenetic changes associated with various forms of cancer. Here we present more than 153 million base pairs representing 99.4% of the euchromatic sequence of chromosome 7, the first metacentric chromosome completed so far. The sequence has excellent concordance with previously established physical and genetic maps, and it exhibits an unusual amount of segmentally duplicated sequence (8.2%), with marked differences between the two arms. Our initial analyses have identified 1,150 protein-coding genes, 605 of which have been confirmed by complementary DNA sequences, and an additional 941 pseudogenes. Of genes confirmed by transcript sequences, some are polymorphic for mutations that disrupt the reading frame. PMID:12853948

  7. Chromosomal aberrations induced by alpha particles

    International Nuclear Information System (INIS)

    The chromosomal aberrations produced by the ionizing radiation are commonly used when it is necessary to establish the exposure dose of an individual, it is a study that is used like complement of the traditional physical systems and its application is only in cases in that there is doubt about what indicates the conventional dosimetry. The biological dosimetry is based on the frequency of aberrations in the chromosomes of the lymphocytes of the individual in study and the dose is calculated taking like reference to the dose-response curves previously generated In vitro. A case of apparent over-exposure to alpha particles to which is practiced analysis of chromosomal aberrations to settle down if in fact there was exposure and as much as possible, to determine the presumed dose is presented. (Author)

  8. Can molecular cell biology explain chromosome motions?

    Directory of Open Access Journals (Sweden)

    Gagliardi L

    2011-05-01

    Full Text Available Abstract Background Mitotic chromosome motions have recently been correlated with electrostatic forces, but a lingering "molecular cell biology" paradigm persists, proposing binding and release proteins or molecular geometries for force generation. Results Pole-facing kinetochore plates manifest positive charges and interact with negatively charged microtubule ends providing the motive force for poleward chromosome motions by classical electrostatics. This conceptual scheme explains dynamic tracking/coupling of kinetochores to microtubules and the simultaneous depolymerization of kinetochore microtubules as poleward force is generated. Conclusion We question here why cells would prefer complex molecular mechanisms to move chromosomes when direct electrostatic interactions between known bound charge distributions can accomplish the same task much more simply.

  9. Chromosome aberration analysis for biological dosimetry: a review

    International Nuclear Information System (INIS)

    Among various biological dosimetry techniques, dicentric chromosome aberration method appears to be the method of choice in analysing accidental radiation exposure in most of the laboratories. The major advantage of this method is its sensitivity as the number of dicentric chromosomes present in control population is too small and more importantly radiation induces mainly dicentric chromosome aberration among unstable aberration. This report brings out the historical development of various cytogenetic methods, the basic structure of DNA, chromosomes and different forms of chromosome aberrations. It also highlights the construction of dose-response curve for dicentric chromosome and its use in the estimation of radiation dose. (author)

  10. An approach to automated chromosome analysis

    International Nuclear Information System (INIS)

    The methods of approach developed with a view to automatic processing of the different stages of chromosome analysis are described in this study divided into three parts. Part 1 relates the study of automated selection of metaphase spreads, which operates a decision process in order to reject ail the non-pertinent images and keep the good ones. This approach has been achieved by Computing a simulation program that has allowed to establish the proper selection algorithms in order to design a kit of electronic logical units. Part 2 deals with the automatic processing of the morphological study of the chromosome complements in a metaphase: the metaphase photographs are processed by an optical-to-digital converter which extracts the image information and writes it out as a digital data set on a magnetic tape. For one metaphase image this data set includes some 200 000 grey values, encoded according to a 16, 32 or 64 grey-level scale, and is processed by a pattern recognition program isolating the chromosomes and investigating their characteristic features (arm tips, centromere areas), in order to get measurements equivalent to the lengths of the four arms. Part 3 studies a program of automated karyotyping by optimized pairing of human chromosomes. The data are derived from direct digitizing of the arm lengths by means of a BENSON digital reader. The program supplies' 1/ a list of the pairs, 2/ a graphic representation of the pairs so constituted according to their respective lengths and centromeric indexes, and 3/ another BENSON graphic drawing according to the author's own representation of the chromosomes, i.e. crosses with orthogonal arms, each branch being the accurate measurement of the corresponding chromosome arm. This conventionalized karyotype indicates on the last line the really abnormal or non-standard images unpaired by the program, which are of special interest for the biologist. (author)

  11. Chromosome Evolution and Genome Miniaturization in Minifish

    Science.gov (United States)

    Liu, Shaojun; Hui, Tan Heok; Tan, Sze Ley; Hong, Yunhan

    2012-01-01

    Background Paedocypris is a newly established genus of fish in Southeast Asia. Paedocypris is characterized by several unique features, including a tiny adult size (thus named miniature fish or minifish), fragmentary habitats of acidic peat blackwater swamps, an unusual reproduction mode and truncated development. These peculiarities lend themselves excellent for studying chromosome evolution and rapid speciation in vertebrates but also make them highly controversial for the phylogenetic position. Methodology and Principal Findings We have established an organ procedure to prepare chromosome spreads from tiny organs of minifish and performed a cytogenetic study on two species of the genus Paedocypris, namely P. carbunculus (Pc) and P. sp. “Singkep” (Ps). We found 30 and 34 chromosomes in diploid cells of Pc and Ps, respectively, which are unusual in teleost fishes. The diploid metaphase has 5 pairs of metacentrics and 7 pairs of subtelocentrics in Pc compared to 3 pairs of metacentrics and 11 pairs of subtelocentrics in Ps, whereas the haploid metaphase contains 5 metacentrics and 7 subtelocentrics in Pc compared to 3 metacentrics and 11 subtelocentrics Ps. Chromosome behavior in first meiosis revealed the presence of a chromosomal ring consisting of 2 metacentrics in Pc, suggesting that centric fusion rather than fission was responsible for the karyotypic evolution from Ps to Pc. Flow cytometry revealed that Pc had a 45% nuclear staining intensity relative to medaka whose genome is 700 Mb in size and contains 0.81 pg DNA. The Pc genome should have 315 Mb in length and 0.36 pg of DNA, which represent one of the smallest values in vertebrates, suggesting genome miniaturization in this organism. Conclusions Our data demonstrate that gross chromosome rearrangements and genome miniaturization have accompanied the evolution of Paedocypris fishes. Our data also place Paedocypris outside currently described taxa of the Cypriniformes. PMID:22615970

  12. Horizontal transfer of supernumerary chromosomes in fungi.

    Science.gov (United States)

    van der Does, H Charlotte; Rep, Martijn

    2012-01-01

    Several species of filamentous fungi contain so-called dispensable or supernumerary chromosomes. These chromosomes are dispensable for the fungus to survive, but may carry genes required for specialized functions, such as infection of a host plant. It has been shown that at least some dispensable chromosomes are able to transfer horizontally (i.e., in the absence of a sexual cycle) from one fungal strain to another. In this paper, we describe a method by which this can be shown. Horizontal chromosome transfer (HCT) occurs during co-incubation of two strains. To document the actual occurrence of HCT, it is necessary to select for HCT progeny. This is accomplished by transforming two different drug-resistance genes into the two parent strains before their co-incubation. In one of the strains (the "donor"), a drug-resistance gene should be integrated in a chromosome of which the propensity for HCT is under investigation. In the "tester" or "recipient" strain, another drug-resistance gene should be integrated somewhere in the core genome. In this way, after co-incubation, HCT progeny can be selected on plates containing both drugs. HCT can be initiated with equal amounts of asexual spores of both strains, plated on regular growth medium for the particular fungus, followed by incubation until new asexual spores are formed. The new asexual spores are then harvested and plated on plates containing both drugs. Double drug-resistant colonies that appear should carry at least one chromosome from each parental strain. Finally, double drug-resistant strains need to be analysed to assess whether HCT has actually occurred. This can be done by various genome mapping methods, like CHEF-gels, AFLP, RFLP, PCR markers, optical maps, or even complete genome sequencing. PMID:22183669

  13. Chromosome anomalies in mouse oocytes after irradiation

    International Nuclear Information System (INIS)

    We investigated the cytogenetic effects of X-rays on unfertilized mouse oocytes. NMRI females received an irradiation with 0, 22.2, 66.6, 200, and 600 R during the preovulatory phase 3 hrs after HCG (human chorionic gonadotrophin). This is a stage during oogenesis in which the oocytes pass from late dictyotene to diakinesis. Chromosome anlysis was per formed after ovulation at metaphase II. From these experiments we can draw the following conclusions: X-rays induced during the preovulatory phase a high number of chromosome anomalies. Among these, structural anomalies prevail. 7 out of 144 ovulated oocytes in matched controls carried such an abnormality, whereas after irradiation we observed with 22.2, 66.6, 200, and 600 R, 11 out of 72, 34 out of 108, 89 out of 102, and 122 out of 124, respectively. Irradiation seems also to affect the chromosome segregation during the 1. meiotic division, as we observed after 22.2, 66.6 and 200 R a total of 6 oocytes out of 204 with a supernummary chromosome. In controls, however, no hyperploidy was found in 143 ova. This increase, however, was not significant. Chromosome anomalies, e.g. breaks and deletions that go back to a one-break event increased linearly with increasing dose. Exchanges, however, going back to two-break events fittet best to the linear-quadratic dose-response model. The dose of 600 R seems to represent a kind of borderline in this experiment, because nearly all (122 out 124) carried at least one structural chromosome anomaly. It is also this dose after which the highest frequency of reciprocal translocations was observed in a humpshaped slope in spermatocytes after irradiation of spermatogonia (Preston and Brewen, 1973). With an increasing dosage up to 1,200 R the frequency of translocations decrease again. The elimination of cells, crossing this borderline, might be due to genetic or non-genetic effects. (orig./GSE)

  14. Chromosomal phylogeny and evolution of gibbons (Hylobatidae).

    Science.gov (United States)

    Müller, Stefan; Hollatz, Melanie; Wienberg, Johannes

    2003-11-01

    Although human and gibbons are classified in the same primate superfamily (Hominoidae), their karyotypes differ by extensive chromosome reshuffling. To date, there is still limited understanding of the events that shaped extant gibbon karyotypes. Further, the phylogeny and evolution of the twelve or more extant gibbon species (lesser apes, Hylobatidae) is poorly understood, and conflicting phylogenies have been published. We present a comprehensive analysis of gibbon chromosome rearrangements and a phylogenetic reconstruction of the four recognized subgenera based on molecular cytogenetics data. We have used two different approaches to interpret our data: (1) a cladistic reconstruction based on the identification of ancestral versus derived chromosome forms observed in extant gibbon species; (2) an approach in which adjacent homologous segments that have been changed by translocations and intra-chromosomal rearrangements are treated as discrete characters in a parsimony analysis (PAUP). The orangutan serves as an "outgroup", since it has a karyotype that is supposed to be most similar to the ancestral form of all humans and apes. Both approaches place the subgenus Bunopithecus as the most basal group of the Hylobatidae, followed by Hylobates, with Symphalangus and Nomascus as the last to diverge. Since most chromosome rearrangements observed in gibbons are either ancestral to all four subgenera or specific for individual species and only a few common derived rearrangements at subsequent branching points have been recorded, all extant gibbons may have diverged within relatively short evolutionary time. In general, chromosomal rearrangements produce changes that should be considered as unique landmarks at the divergence nodes. Thus, molecular cytogenetics could be an important tool to elucidate phylogenies in other species in which speciation may have occurred over very short evolutionary time with not enough genetic (DNA sequence) and other biological divergence to

  15. Molecular mapping of chromosomes 17 and X

    Energy Technology Data Exchange (ETDEWEB)

    Barker, D.F.

    1989-01-01

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

  16. AT cells are not radiosensitive for simple chromosomal exchanges at low dose

    Energy Technology Data Exchange (ETDEWEB)

    Hada, Megumi; Huff, Janice L.; Patel, Zarana S. [USRA Division of Life Sciences, Houston, TX 77058 (United States); Kawata, Tetsuya [Department of Radiology, School of Medicine, Keio University, Tokyo (Japan); Pluth, Janice M. [Lawrence Berkeley National Laboratory, Life Sciences Division, One Cyclotron Road, Building 74, Berkeley, CA 94720 (United States); George, Kerry A. [Wyle, 1290 Hercules Drive, Houston, TX 77058 (United States); Cucinotta, Francis A., E-mail: Francis.A.Cucinotta@nasa.gov [NASA, Lyndon B. Johnson Space Center, 2101 NASA Parkway, Houston, TX 77058 (United States)

    2011-11-01

    Cells deficient in ATM (product of the gene that is mutated in ataxia telangiectasia patients) or NBS (product of the gene mutated in the Nijmegen breakage syndrome) show increased yields of both simple and complex chromosomal aberrations after high doses (>0.5 Gy) of ionizing radiation (X-rays or {gamma}-rays), however less is known on how these cells respond at low dose. Previously we had shown that the increased chromosome aberrations in ATM and NBS defective lines was due to a significantly larger quadratic dose-response term compared to normal fibroblasts for both simple and complex exchanges. The linear dose-response term for simple exchanges was significantly higher in NBS cells compared to wild type cells, but not for AT cells. However, AT cells have a high background level of exchanges compared to wild type or NBS cells that confounds the understanding of low dose responses. To understand the sensitivity differences for high to low doses, chromosomal aberration analysis was first performed at low dose-rates (0.5 Gy/d), and results provided further evidence for the lack of sensitivity for exchanges in AT cells below doses of 1 Gy. Normal lung fibroblast cells treated with KU-55933, a specific ATM kinase inhibitor, showed increased numbers of exchanges at a dose of 1 Gy and higher, but were similar to wild type cells at 0.5 Gy or below. These results were confirmed using siRNA knockdown of ATM. The present study provides evidence that the increased radiation sensitivity of AT cells for chromosomal exchanges found at high dose does not occur at low dose.

  17. Protein kinases associated with the yeast phosphoproteome

    Directory of Open Access Journals (Sweden)

    Munn Alan L

    2006-01-01

    Full Text Available Abstract Background Protein phosphorylation is an extremely important mechanism of cellular regulation. A large-scale study of phosphoproteins in a whole-cell lysate of Saccharomyces cerevisiae has previously identified 383 phosphorylation sites in 216 peptide sequences. However, the protein kinases responsible for the phosphorylation of the identified proteins have not previously been assigned. Results We used Predikin in combination with other bioinformatic tools, to predict which of 116 unique protein kinases in yeast phosphorylates each experimentally determined site in the phosphoproteome. The prediction was based on the match between the phosphorylated 7-residue sequence and the predicted substrate specificity of each kinase, with the highest weight applied to the residues or positions that contribute most to the substrate specificity. We estimated the reliability of the predictions by performing a parallel prediction on phosphopeptides for which the kinase has been experimentally determined. Conclusion The results reveal that the functions of the protein kinases and their predicted phosphoprotein substrates are often correlated, for example in endocytosis, cytokinesis, transcription, replication, carbohydrate metabolism and stress response. The predictions link phosphoproteins of unknown function with protein kinases with known functions and vice versa, suggesting functions for the uncharacterized proteins. The study indicates that the phosphoproteins and the associated protein kinases represented in our dataset have housekeeping cellular roles; certain kinases are not represented because they may only be activated during specific cellular responses. Our results demonstrate the utility of our previously reported protein kinase substrate prediction approach (Predikin as a tool for establishing links between kinases and phosphoproteins that can subsequently be tested experimentally.

  18. Tracking chromosome evolution in southern African gerbils using flow-sorted chromosome paints.

    Science.gov (United States)

    Knight, L I; Ng, B L; Cheng, W; Fu, B; Yang, F; Rambau, R V

    2013-01-01

    Desmodillus and Gerbilliscus (formerly Tatera) comprise a monophyletic group of gerbils (subfamily Gerbillinae) which last shared an ancestor approximately 8 million years ago; diploid chromosome number variation among the species ranges from 2n = 36 to 2n = 50. In an attempt to shed more light on chromosome evolution and speciation in these rodents, we compared the karyotypes of 7 species, representing 3 genera, based on homology data revealed by chromosome painting with probes derived from flow-sorted chromosomes of the hairy footed gerbil, Gerbillurus paeba (2n = 36). The fluorescent in situ hybridization data revealed remarkable genome conservation: these species share a high proportion of conserved chromosomes, and differences are due to 10 Robertsonian (Rb) rearrangements (3 autapomorphies, 3 synapomorphies and 4 hemiplasies/homoplasies). Our data suggest that chromosome evolution in Desmodillus occurred at a rate of ~1.25 rearrangements per million years (Myr), and that the rate among Gerbilliscus over a time period spanning 8 Myr is also ~1.25 rearrangements/Myr. The recently diverged Gerbillurus (G. tytonis and G. paeba) share an identical karyotype, while Gerbilliscus kempi, G. afra and G. leucogaster differ by 6 Rb rearrangements (a rate of ~1 rearrangement/Myr). Thus, our data suggests a very slow rate of chromosomal evolution in Southern African gerbils. PMID:23652816

  19. 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...

  20. Cancer chromosomal instability: therapeutic and diagnostic challenges.

    Science.gov (United States)

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

    2012-06-01

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

  1. Differential phosphorylation of ribosomal acidic proteins from yeast cell by two endogenous protein kinases: casein kinase-2 and 60S kinase

    International Nuclear Information System (INIS)

    The native 80S ribosomes isolated from ''Saccharomyces cerevisiae'' (strain W303) cells was phosphorylated by two endogenous protein kinases: multifunctional casein kinase-2 (CK-2) and specific 60S kinase. Three acidic proteins within the 60S ribosomal subunit: YP1β, YP1β' and YP2α are phosphorylated by both kinases. The other two proteins: YP1α and YP2β are predominantly phosphorylated by CK-2 but not by 60S kinase. This was confirmed in the experiment with the recombinant protein, YP2β, as a substrate, which is practically not phosphorylated by specific 60S kinase. These results together with the previous data based on the target amino-acid sequences suggest that, in addition to the multifunctional casein kinase-2 and specific 60S kinase, there exist probably other protein kinase(s) which phosphorylate the ribosomal acidic proteins in the cell. (author). 23 refs, 3 figs, 1 tab

  2. Aging-associated dysfunction of Akt/protein kinase B: S-nitrosylation and acetaminophen intervention.

    Directory of Open Access Journals (Sweden)

    Miaozong Wu

    Full Text Available BACKGROUND: Aged skeletal muscle is characterized by an increased incidence of metabolic and functional disorders, which if allowed to proceed unchecked can lead to increased morbidity and mortality. The mechanism(s underlying the development of these disorders in aging skeletal muscle are not well understood. Protein kinase B (Akt/PKB is an important regulator of cellular metabolism and survival, but it is unclear if aged muscle exhibits alterations in Akt function. Here we report a novel dysfunction of Akt in aging muscle, which may relate to S-nitrosylation and can be prevented by acetaminophen intervention. PRINCIPAL FINDINGS: Compared to 6- and 27-month rats, the phosphorylation of Akt (Ser473 and Thr308 was higher in soleus muscles of very aged rats (33-months. Paradoxically, these increases in Akt phosphorylation were associated with diminished mammalian target of rapamycin (mTOR phosphorylation, along with decreased levels of insulin receptor beta (IR-beta, phosphoinositide 3-kinase (PI3K, phosphatase and tensin homolog deleted on chromosome 10 (PTEN and phosphorylation of phosphoinositide-dependent kinase-1 (PDK1 (Ser241. In vitro Akt kinase measurements and ex vivo muscle incubation experiments demonstrated age-related impairments of Akt kinase activity, which were associated with increases in Akt S-nitrosylation and inducible nitric oxide synthase (iNOS. Impairments in Akt function occurred parallel to increases in myocyte apoptosis and decreases in myocyte size and the expression of myosin and actin. These age-related disorders were attenuated by treating aged (27-month animals with acetaminophen (30 mg/kg body weight/day for 6-months. CONCLUSIONS: These data demonstrate that Akt dysfunction and increased S-nitrosylation of Akt may contribute to age-associated disorders in skeletal muscle and that acetaminophen may be efficacious for the treatment of age-related muscle dysfunction.

  3. Human chromosome 'painting' probes used to measure chromosome translocations in non-human primates: extrapolations from monkey to man

    International Nuclear Information System (INIS)

    Chromosome painting with a probe specific for human chromosome 4 was used to 'paint' monkey chromosomes to measure the persistence of translocations in peripheral blood lymphocytes of a rhesus monkey exposed to ionising radiation more than 25 years ago. The human probe painted the entire length of two large rhesus and cynomolgus monkey chromosomes with no cross hybridisation to other chromosomes, facilitating rapid detection of chromosome translocations. Translocation frequency measured in one monkey was significantly higher than that for unirradiated animals. The use of human probes to obtain cytogenetic data from Macaca species irradiated years previously or exposed to chemical clastogens makes this genus an excellent model for studying genetic damage. (author)

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

    OpenAIRE

    Machiela, Mitchell J.; Zhou, Weiyin; Karlins, Eric; Sampson, Joshua N.; Neal D Freedman; 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.

    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 ...

  5. Assignment of the human cytidine deaminase (CDA) gene to chromosome 1 band p35-p36.2

    Energy Technology Data Exchange (ETDEWEB)

    Saccone, S.; Andreozzi, L.; Della Valle, G. [Universita di Pavia (Italy)] [and others

    1994-08-01

    The enzyme cytidine deaminase (EC 3.5.4.12; CDA) catalyzes the hydrolytic deamination of cytidine or deoxycytidine to uridine or deoxyuridine, respectively. It can also catalyze the deamination of cytosine nucleoside analogues such as cytosine arabinoside and 5-azacytidine, which results in a loss of their cytotoxic and antitumor activity. Cytosine arabinoside is used in the treatment of acute myeloid leukemia, and the antileukemic activity of the drug is dependent on phosphorylation by deoxycytidine kinase. The occurrence of clinical cytosine arabinoside resistance is one of the main problems in the successful treatment of acute myeloid leukemia. Resistance to the drug has been ascribed to functional deoxycytidine kinase deficiency and to increased expression of the CDA gene. In this study, we report on the isolation of a CDA genomic fragment and its use as a probe for the chromosomal localization of the human CDA gene by in situ hybridization. 9 refs., 1 fig.

  6. Human protein kinase C lota gene (PRKC1) is closely linked to the BTK gene in Xq21.3

    Energy Technology Data Exchange (ETDEWEB)

    Mazzarella, R.; Jones, C.; Schlessinger, D. [Washington Univ. School of Medicine, St. Louis, MO (United States)] [and others

    1995-04-10

    The human X chromosome contains many disease loci, but only a small number of X-linked genes have been cloned and characterized. One approach to finding genes in genomic DNA uses partial sequencing of random cDNAs to develop {open_quotes}expressed sequence tags{close_quotes} (ESTs). Many authors have recently reported chromosomal localization of such ESTs using hybrid panels. Twenty ESTs specific for the X chromosome have been localized to defined regions with somatic cell hybrids, and 12 of them have been physically linked to markers that detect polymorphisms. One of these ESTs, EST02087, was physically linked in a 650-kb contig to the GLA ({alpha}-galactosidase) gene involved in Fabry disease. A comparison of this contig with a 7.5-Mb YAC contig indicated that this gene is also within 250 kb of the src-like protein-tyrosine kinase BTK (X-linked agammaglobulinemia protein-tyrosine kinase) gene in Xq21.3. 14 refs., 1 fig.

  7. Phosphorylation of Sli15 by Ipl1 Is Important for Proper CPC Localization and Chromosome Stability in Saccharomyces cerevisiae

    OpenAIRE

    Makrantoni, Vasso; Corbishley, Stephen J.; Rachidi, Najma; Morrice, Nicholas A; Robinson, David A.; Stark, Michael J. R.

    2014-01-01

    The chromosomal passenger complex (CPC) is a key regulator of eukaryotic cell division, consisting of the protein kinase Aurora B/Ipl1 in association with its activator (INCENP/Sli15) and two additional proteins (Survivin/Bir1 and Borealin/Nbl1). Here we have identified multiple sites of CPC autophosphorylation on yeast Sli15 that are located within its central microtubule-binding domain and examined the functional significance of their phosphorylation by Ipl1 through mutation of these sites,...

  8. Crystal Structure of Pyridoxal Kinase from the Escherichia coli pdxK Gene: Implications for the Classification of Pyridoxal Kinases

    OpenAIRE

    Safo, Martin K.; Musayev, Faik N.; di Salvo, Martino L.; Hunt, Sharyn; Claude, Jean-Baptiste; Schirch, Verne

    2006-01-01

    The pdxK and pdxY genes have been found to code for pyridoxal kinases, enzymes involved in the pyridoxal phosphate salvage pathway. Two pyridoxal kinase structures have recently been published, including Escherichia coli pyridoxal kinase 2 (ePL kinase 2) and sheep pyridoxal kinase, products of the pdxY and pdxK genes, respectively. We now report the crystal structure of E. coli pyridoxal kinase 1 (ePL kinase 1), encoded by a pdxK gene, and an isoform of ePL kinase 2. The structures were deter...

  9. ATP and AMP Mutually Influence Their Interaction with the ATP-binding Cassette (ABC) Adenylate Kinase Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) at Separate Binding Sites*

    OpenAIRE

    Randak, Christoph O.; Dong, Qian; Ver Heul, Amanda R.; Elcock, Adrian H.; Welsh, Michael J.

    2013-01-01

    Cystic fibrosis transmembrane conductance regulator (CFTR) is an anion channel in the ATP-binding cassette (ABC) transporter protein family. In the presence of ATP and physiologically relevant concentrations of AMP, CFTR exhibits adenylate kinase activity (ATP + AMP ⇆ 2 ADP). Previous studies suggested that the interaction of nucleotide triphosphate with CFTR at ATP-binding site 2 is required for this activity. Two other ABC proteins, Rad50 and a structural maintenance of chromosome protein, ...

  10. Activation of RAF1 (c-RAF by the Marine Alkaloid Lasonolide A Induces Rapid Premature Chromosome Condensation

    Directory of Open Access Journals (Sweden)

    Rozenn Jossé

    2015-06-01

    Full Text Available Lasonolide A (LSA, a potent antitumor polyketide from the marine sponge, Forcepia sp., induces rapid and reversible protein hyperphosphorylation and premature chromosome condensation (PCC at nanomolar concentrations independent of cyclin-dependent kinases. To identify cellular targets of LSA, we screened 2951 shRNAs targeting a pool of human kinases and phosphatases (1140 RefSeqs to identify genes that modulate PCC in response to LSA. This led to the identification of RAF1 (C-RAF as a mediator of LSA-induced PCC, as shRNAs against RAF1 conferred resistance to LSA. We found that LSA induced RAF1 phosphorylation on Serine 338 within minutes in human colorectal carcinoma HCT-116, ovarian carcinoma OVCAR-8, and Burkitt’s lymphoma CA46 cell lines. RAF1 depletion by siRNAs attenuated LSA-induced PCC in HCT-116 and OVCAR-8 cells. Furthermore, mouse embryonic fibroblasts (MEF with homozygous deletion in Raf1, but not deletion in the related kinase Braf, were resistant to LSA-induced PCC. Complementation of Raf1−/− MEFs with wild-type human RAF1, but not with kinase-dead RAF1 mutant, restored LSA-induced PCC. Finally, the Raf inhibitor sorafenib, but not the MEK inhibitor AZD6244, effectively suppressed LSA-induced PCC. Our findings implicate a previously unknown, MAPK-independent role of RAF1 in chromatin condensation and potent activation of this pathway by LSA.

  11. Understanding Chromosome Disorders and their Implications for Special Educators

    Directory of Open Access Journals (Sweden)

    Linda Gilmore

    2014-03-01

    Full Text Available More children are now being diagnosed with chromosome abnormalities. Some chromosome disorder syndromes are relatively well known; while others are so rare that there is only limited evidence about their likely impact on learning and development. For educators, a basic level of knowledge about chromosome abnormalities is important for understanding the literature and communicating with families and professionals. This paper describes chromosomes, and the numerical and structural anomalies that can occur, usually spontaneously during early cell division. Distinctive features of various chromosome syndromes are summarised before a discussion of the rare chromosome disorders that are labelled, not with a syndrome name, but simply by a description of the chromosome number, size and shape. Because of the potential within-group variability that characterises syndromes, and the scarcity of literature about the rare chromosome disorders, expectations for learning and development of individual students need to be based on the range of possible outcomes that may be achievable.

  12. Function of the Sex Chromosomes in Mammalian Fertility

    OpenAIRE

    Heard, Edith; Turner, James

    2011-01-01

    In female germ cells, the inactive X chromosome is reactivated before meiosis and thereafter remains active. In contrast, the X chromosome in males is inactivated during meiosis, and silencing is largely maintained during spermiogenesis.

  13. Mapping and ordered cloning of the human X chromosome

    Energy Technology Data Exchange (ETDEWEB)

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

    1992-12-01

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

  14. Physiological roles of mitogen-activated-protein-kinase-activated p38-regulated/activated protein kinase

    Institute of Scientific and Technical Information of China (English)

    Sergiy; Kostenko; Gianina; Dumitriu; Kari; Jenssen; Lgreid; Ugo; Moens

    2011-01-01

    Mitogen-activated protein kinases(MAPKs)are a family of proteins that constitute signaling pathways involved in processes that control gene expression,cell division, cell survival,apoptosis,metabolism,differentiation and motility.The MAPK pathways can be divided into conventional and atypical MAPK pathways.The first group converts a signal into a cellular response through a relay of three consecutive phosphorylation events exerted by MAPK kinase kinases,MAPK kinase,and MAPK.Atypical MAPK pathways are not organized into this three-tiered cascade.MAPK that belongs to both conventional and atypical MAPK pathways can phosphorylate both non-protein kinase substrates and other protein kinases.The latter are referred to as MAPK-activated protein kinases.This review focuses on one such MAPK-activated protein kinase,MAPK-activated protein kinase 5(MK5)or p38-regulated/activated protein kinase(PRAK).This protein is highly conserved throughout the animal kingdom and seems to be the target of both conventional and atypical MAPK pathways.Recent findings on the regulation of the activity and subcellular localization,bona fide interaction partners and physiological roles of MK5/PRAK are discussed.

  15. Mitogen-activated protein kinases in atherosclerosis

    Directory of Open Access Journals (Sweden)

    Dorota Bryk

    2014-01-01

    Full Text Available Intracellular signalling cascades, in which MAPK (mitogen-activated protein kinases intermediate, are responsible for a biological response of a cell to an external stimulus. MAP kinases, which include ERK1/2 (extracellular signalling-regulated kinase, JNK (c-Jun N-terminal kinase and p 38 MAPK, regulate the activity of many proteins, enzymes and transcription factors and thus have a wide spectrum of biological effects. Many basic scientific studies have defined numerous details of their pathway organization and activation. There are also more and more studies suggesting that individual MAP kinases probably play an important role in the pathogenesis of atherosclerosis. They may mediate inflammatory processes, endothelial cell activation, monocyte/macrophage recruitment and activation, smooth muscle cell proliferation and T-lymphocyte differentiation, all of which represent crucial mechanisms involved in pathogenesis of atherosclerosis. The specific inhibition of an activity of the respective MAP kinases may prove a new therapeutic approach to attenuate atherosclerotic plaque formation in the future. In this paper, we review the current state of knowledge concerning MAP kinase-dependent cellular and molecular mechanisms underlying atherosclerosis.

  16. [Mitogen-activated protein kinases in atherosclerosis].

    Science.gov (United States)

    Bryk, Dorota; Olejarz, Wioletta; Zapolska-Downar, Danuta

    2014-01-01

    Intracellular signalling cascades, in which MAPK (mitogen-activated protein kinases) intermediate, are responsible for a biological response of a cell to an external stimulus. MAP kinases, which include ERK1/2 (extracellular signalling-regulated kinase), JNK (c-Jun N-terminal kinase) and p 38 MAPK, regulate the activity of many proteins, enzymes and transcription factors and thus have a wide spectrum of biological effects. Many basic scientific studies have defined numerous details of their pathway organization and activation. There are also more and more studies suggesting that individual MAP kinases probably play an important role in the pathogenesis of atherosclerosis. They may mediate inflammatory processes, endothelial cell activation, monocyte/macrophage recruitment and activation, smooth muscle cell proliferation and T-lymphocyte differentiation, all of which represent crucial mechanisms involved in pathogenesis of atherosclerosis. The specific inhibition of an activity of the respective MAP kinases may prove a new therapeutic approach to attenuate atherosclerotic plaque formation in the future. In this paper, we review the current state of knowledge concerning MAP kinase-dependent cellular and molecular mechanisms underlying atherosclerosis. PMID:24491891

  17. Improved prenatal detection of chromosomal anomalies

    DEFF Research Database (Denmark)

    Frøslev-Friis, Christina; Hjort-Pedersen, Karina; Henriques, Carsten U;

    2011-01-01

    Prenatal screening for karyotype anomalies takes place in most European countries. In Denmark, the screening method was changed in 2005. The aim of this study was to study the trends in prevalence and prenatal detection rates of chromosome anomalies and Down syndrome (DS) over a 22-year period....

  18. Precise Centromere Positioning on Chicken Chromosome 3

    NARCIS (Netherlands)

    Zlotina, A.; Galkina, S.A.; Krasikova, A.; Crooijmans, R.P.M.A.; Groenen, M.A.M.; Gaginskaya, E.; Deryusheva, S.

    2010-01-01

    Despite the progress of the chicken (Gallus gallus) genome sequencing project, the centromeric sequences of most macrochromosomes remain unknown. This makes it difficult to determine centromere positions in the genome sequence assembly. Using giant lampbrush chromosomes from growing oocytes, we anal

  19. 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.

  20. Johannsen's criticism of the chromosome theory.

    Science.gov (United States)

    Roll-Hansen, Nils

    2014-01-01

    The genotype theory of Wilhelm Johannsen (1857-1927) was an important contribution to the founding of classical genetics. This theory built on Johannsen's experimental demonstration that hereditary change is discontinuous, not continuous as had been widely assumed. Johannsen is also known for his criticism of traditional Darwinian evolution by natural selection, as well as his criticism of the classical Mendelian chromosome theory of heredity. He has often been seen as one of the anti-Darwinians that caused the "eclipse of Darwinism" in the early 20th century, before it was saved by the Modern Synthesis. This article focuses on Johannsen's criticism of the chromosome theory. He was indeed skeptical of the notion of the chromosomes as the sole carriers of heredity, but he praised the mapping of Mendelian genes on the chromosomes as a major step forward. Johannsen objected that these genes could not account for the whole of heredity, and that the stability of the genotype depended on much more than the stability of Mendelian genes. For Johannsen, the genotype, as a property of the whole organism, was the fundamental and empirically well-established entity. PMID:25345701

  1. Chameleons out of disguise: sex chromosomes revealed

    Czech Academy of Sciences Publication Activity Database

    Rovatsos, M.; Johnson Pokorná, Martina; Altmanová, M.; Kratochvíl, L.

    Brno: Ústav biologie obratlovců AV ČR, 2015 - (Bryja, J.; Řehák, Z.; Zukal, J.). s. 212-212 ISBN 978-80-87189-18-4. [Zoologické dny. 12.02.2015-13.02.2015, Brno] Institutional support: RVO:67985904 Keywords : sex chromosomes Subject RIV: EG - Zoology

  2. The evolution of sex chromosomes in papaya

    Czech Academy of Sciences Publication Activity Database

    Yu, Qingyi; Moore, Paul H.; Alam, Maqsudul; Jiang, Jiming; Paterson, Andrew H.; Vyskot, Boris; Ming, Ray

    San Diego, 2006. W340-W340. [Plant & Animal Genomes XIV Conference. 14.01.2006-18.01.2006, San Diego] R&D Projects: GA ČR(CZ) GA521/06/0056; GA MŠk(CZ) LC06004 Institutional research plan: CEZ:AV0Z50040507 Keywords : evolution * sex chromosomes * papaya Subject RIV: BO - Biophysics

  3. First trimester ultrasound screening of chromosomal abnormalities

    Directory of Open Access Journals (Sweden)

    Trninić-Pjević Aleksandra

    2007-01-01

    Full Text Available Introduction: A retrocervical subcutaneous collection of fluid at 11-14 weeks of gestation, can be visualized by ultrasound as nuchal translucency (NT. Objective. To examine the distribution of fetal nuchal translucency in low risk population, to determine the detection rate of chromosomal abnormalities in the population of interest based on maternal age and NT measurement. Method. Screening for chromosomal defects, advocated by The Fetal Medicine Foundation (FMF, was performed in 1,341 pregnancies in the period January 2000 - April 2004. Initial risk for chromosomal defects (based on maternal and gestational age and corrected risk, after the NT measurement, were calculated. Complete data were collected from 1,048 patients. Results. Out of 1,048 pregnancies followed, 8 cases of Down’s syndrome were observed, 7 were detected antenatally and 6 out of 7 were detected due to screening that combines maternal age and NT measurement. According to our results, sensitivity of the screening for aneuploidies based on maternal age alone was 12.5% and false positive rate 13.1%, showing that screening based on NT measurement is of great importance. Screening by a combination of maternal age and NT, and selecting a screening-positive group for invasive testing enabled detection of 75% of fetuses with trisomy 21. Conclusion. In screening for chromosomal abnormalities, an approach which combines maternal age and NT is effective and increases the detection rate compared to the use of any single test. .

  4. Ring Chromosome 7 in an Indian Woman

    Science.gov (United States)

    Kaur, Anupam; Dhillon, Sumit; Garg, P. D.; Singh, Jai Rup

    2008-01-01

    Background: Ring chromosome 7 [r(7)] is a rare cytogenetic aberration, with only 16 cases (including 3 females) reported in the literature to date. This is the first reported case of r(7) from India. Method: Clinical and cytogenetic investigations were carried out in an adult female with microcephaly and intellectual disability. Results: Ring…

  5. IAPT/IOPB chromosome data 20

    Czech Academy of Sciences Publication Activity Database

    Altinordu, F.; Šumberová, Kateřina; Ankova, T.; Erst, A. S.; Kuzmin, I. V.; Shaulo, D. N.; Plugatar, Y. V.; Baltisberger, M.; Deldago, L.; Gallego Martín, F.; Rico, E.; Lavia, G. I.; Krapovickas, A.; de los Angeles Martines, M.; Lazaroff, Y.; Solis Neffa, V. G.; Ortiz, A. M.; Sivestri, M. C.; Pavlova, D.; Bani, A.; Polido, C. A.; Moraes, A. P.; Forni-Martins, E. R.; Probatova, N. S.; Kazanovsky, S. G.; Barkalov, V. Y.; Rudyka, E. G.; Shatokhina, A. V.; Krivenko, D. A.; Verkhozina, A. V.; Nechaev, V. A.; Romero-da Cruz, M. V.; Wefferling, K. M.; Owen, H. A.; Hoot, S. B.

    2015-01-01

    Roč. 64, č. 6 (2015), s. 1344-1350. ISSN 0040-0262 R&D Projects: GA ČR GB14-36079G Institutional support: RVO:67985939 Keywords : chromosome count * plant s Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.299, year: 2014

  6. Making the Chromosome-Gene-Protein Connection.

    Science.gov (United States)

    Mulvihill, Charlotte

    1996-01-01

    Presents an exercise that demonstrates the chromosome-gene-protein connection using sickle-cell anemia, a genetic disease with a well-characterized molecular basis. Involves connecting changes in DNA to protein outcomes and tying them into the next generation by meiosis and gamete formation with genetic crosses. Motivates students to integrate…

  7. Chromosome Analysis and Sorting Using Flow Cytometry

    Czech Academy of Sciences Publication Activity Database

    Doležel, Jaroslav; Kubaláková, Marie; Čihalíková, Jarmila; Suchánková, Pavla; Šimková, Hana

    New Jersey : Humana Press, 2011 - (Birchler, J.), s. 221-237 ISBN 978-1-61737-956-7 R&D Projects: GA ČR GA521/07/1573; GA MŠk(CZ) LC06004 Institutional research plan: CEZ:AV0Z50380511 Keywords : Chromosome analysis * flow cytometry * root meristems Subject RIV: EB - Genetics ; Molecular Biology

  8. The chromosome 9q subtelomere deletion syndrome

    NARCIS (Netherlands)

    Stewart, D.R.; Kleefstra, T.

    2007-01-01

    The chromosome 9q subtelomere deletion syndrome (9qSTDS) is among the first and most common clinically recognizable syndromes to arise from widespread testing by fluorescent in situ hybridization (FISH) of subtelomere deletions. There are about 50 reported cases worldwide. Affected individuals invar

  9. Progressive segregation of the Escherichia coli chromosome

    DEFF Research Database (Denmark)

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

    2006-01-01

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

  10. The genomics of plant sex chromosomes

    Czech Academy of Sciences Publication Activity Database

    Vyskot, Boris; Hobza, Roman

    2015-01-01

    Roč. 236, JUL 2015 (2015), s. 126-135. ISSN 0168-9452 R&D Projects: GA ČR(CZ) GBP501/12/G090; GA ČR(CZ) GAP501/12/2220 Institutional support: RVO:68081707 Keywords : Y-CHROMOSOME * SILENE-LATIFOLIA * DIOECIOUS PLANT Subject RIV: BO - Biophysics Impact factor: 3.607, year: 2014

  11. Psychoeducational Implications of Sex Chromosome Anomalies

    Science.gov (United States)

    Wodrich, David L.; Tarbox, Jennifer

    2008-01-01

    Numerous anomalies involving the sex chromosomes (X or Y) have been documented and their impact on development, learning, and behavior studied. This article reviews three of these disorders, Turner syndrome, Klinefelter syndrome, and Lesch-Nyhan disease. Each of these three is associated with one or more selective impairments or behavioral…

  12. Mutations in the BCR-ABL1 Kinase Domain and Elsewhere in Chronic Myeloid Leukemia.

    Science.gov (United States)

    Soverini, Simona; de Benedittis, Caterina; Mancini, Manuela; Martinelli, Giovanni

    2015-06-01

    Chronic myeloid leukemia (CML) has been the first human malignancy to be associated, more than 50 years ago, with a consistent chromosomal abnormality--the t(9;22)(q34;q11) chromosomal translocation. The resulting BCR-ABL1 fusion gene, encoding a tyrosine kinase with deregulated activity, has a central role in the pathogenesis of CML. Ancestral or additional genetic events necessary for CML to develop have long been hypothesized but never really demonstrated. CML can successfully be treated with tyrosine kinase inhibitors (TKIs). Mutations in the BCR-ABL1 kinase domain might arise, however, that confer resistance to 1 or more of the currently available TKIs. Hence, the critical role of BCR-ABL1 mutation screening for optimal therapeutic management, with the current gold standard technique, conventional sequencing, likely to be replaced soon by ultra-deep sequencing. Mutations in genes other than BCR-ABL1 include ASXL1, TET2, RUNX1, DNMT3A, EZH2, and TP53 in chronic phase patients and RUNX1, ASXL1, IKZF1, WT1, TET2, NPM1, IDH1, IDH2, NRAS, KRAS, CBL, TP53, CDKN2A, RB1, and GATA-2 mutations in advanced phase patients. The latter also display additional cytogenetic abnormalities, including submicroscopic regions of gain or loss that only single nucleotide polymorphism arrays or array comparative genomic hybridization can detect. Whether whole genome/exome sequencing studies will uncover novel mutations relevant for pathogenesis, progression, and risk-adapted therapy is still unclear. PMID:26297264

  13. A computer simulation of chromosomal instability

    Science.gov (United States)

    Goodwin, E.; Cornforth, M.

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

  14. 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...

  15. The Evolutionary Pathway of X Chromosome Inactivation in Mammals

    OpenAIRE

    Shevchenko, A.; Zakharova, I.; Zakian, S.

    2013-01-01

    X chromosome inactivation is a complex process that occurs in marsupial and eutherian mammals. The process is thought to have arisen during the differentiation of mammalian sex chromosomes to achieve an equal dosage of X chromosome genes in males and females. The differences in the X chromosome inactivation processes in marsupial and eutherian mammals are considered, and the hypotheses on its origin and evolution are discussed in this review.

  16. Characterization of Chenopodium quinoa chromosomes using fish and repetitive sequences

    International Nuclear Information System (INIS)

    Quinoa is one of the underestimated crops, which recently attracted attention. During last few years many efforts were done to save the natural genetic diversity of quinoa cultivars and landraces as well as to obtained new variability by mutagenesis. Plant characteristics based mainly on morphological and molecular markers. Cytogenetic analysis was not used for these studies. Quinoa is an allotetraploid species with 36 small chromosomes. To follow the chromosomal rearrangement cause by spontaneous or induced mutations it is necessary to find cytogenetics markers for chromosomes and chromosome arms. The physical mapping of repetitive DNAs by fluorescent in situ hybridization (FISH) can provide a valuable tool in studies of genome organization and chromosome rearrangements. To characterized quinoa genome several repetitive sequences were used as DNA probes for FISH. Double FISH with rRNA genes as probes allowed to distinguished three pairs of homologue chromosomes. Telomeric repeats hybridisation signals were present only in terminal part of all chromosome arms and no intercalar position was observed. Other tandem repetitive sequence - minisatellite was characteristic for centromeric and pericentromeric region of all quinoa chromosomes although number of repeats differ between loci. It allowed to divided quinoa chromosomes into few groups. Disperse repetitive sequences such as mobile element-like sequences used in this study were detected in all eighteen chromosome pairs. Hybridization signals were characteristics for pericentromeric region of one or both chromosome arms as relatively weak but discrete signals although few chromosomes exhibited signals in intercalary position. Two others repetitive sequences also exhibited disperse organization; however they are not mobile elements. Their FISH signals were spread throughout whole chromosome arms but only one was present on all quinoa chromosomes. The other revealed hybridization signals only on the half of the

  17. On the origin of sex chromosomes from meiotic drive

    OpenAIRE

    Úbeda, Francisco; Patten, Manus M.; Wild, Geoff

    2015-01-01

    Most animals and many plants make use of specialized chromosomes (sex chromosomes) to determine an individual's sex. Best known are the XY and ZW sex-determination systems. Despite having evolved numerous times, sex chromosomes present something of an evolutionary puzzle. At their origin, alleles that dictate development as one sex or the other (primitive sex chromosomes) face a selective penalty, as they will be found more often in the more abundant sex. How is it possible that primitive sex...

  18. Sonographically determined anomalies and outcome in 170 chromosomally abnormal fetuses

    OpenAIRE

    Wladimiroff, Juriy; Bhaggoe, W.; Kristelijn, M. J E; Cohen-Overbeek, Titia; Hollander, Nicolette; Brandenburg, Helen; Los, F.J.

    1995-01-01

    textabstractStructural pathology and outcome were studied in 170 chromosomally abnormal fetuses. Numerical chromosomal abnormalities were established in 158 (93 per cent) cases, of which 110 (71 per cent) represented trisomies, 30 (18 per cent) Turner syndrome, and 18 (11 per cent) triploidy. Structural chromosomal abnormalities were diagnosed in 12 (7 per cent) cases. Gestational age at referral was significantly shorter for pregnancies with Turner syndrome than for the other chromosomal abn...

  19. Balanced Chromosomal Rearrangement in Recurrent Spontaneous Abortions: A Case Report

    OpenAIRE

    Zarifian, Ahmadreza; Farhoodi, Zeinab; Amel, Roya; Mirzaee, Salmeh; Hassanzadeh-Nazarabadi, Mohammad

    2012-01-01

    One of the major causes of spontaneous abortion before the fourth month of pregnancy is chromosomal abnormalities. We report an unusual case of a familial balanced chromosomal translocation in a consanguineous couple who experienced 4 spontaneous abortions. Chromosomal studies were performed on the basis of G-banding technique at high resolution and revealed 46, XX, t (16; 6) (p12; q26) and 46, XY, t (16; 6) (p12; q26) in both partners, which induced such pregnancy complications. Chromosomal ...

  20. 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.

  1. Chromosomes. A comprehensive Xist interactome reveals cohesin repulsion and an RNA-directed chromosome conformation.

    Science.gov (United States)

    Minajigi, Anand; Froberg, John E; Wei, Chunyao; Sunwoo, Hongjae; Kesner, Barry; Colognori, David; Lessing, Derek; Payer, Bernhard; Boukhali, Myriam; Haas, Wilhelm; Lee, Jeannie T

    2015-07-17

    The inactive X chromosome (Xi) serves as a model to understand gene silencing on a global scale. Here, we perform "identification of direct RNA interacting proteins" (iDRiP) to isolate a comprehensive protein interactome for Xist, an RNA required for Xi silencing. We discover multiple classes of interactors-including cohesins, condensins, topoisomerases, RNA helicases, chromatin remodelers, and modifiers-that synergistically repress Xi transcription. Inhibiting two or three interactors destabilizes silencing. Although Xist attracts some interactors, it repels architectural factors. Xist evicts cohesins from the Xi and directs an Xi-specific chromosome conformation. Upon deleting Xist, the Xi acquires the cohesin-binding and chromosomal architecture of the active X. Our study unveils many layers of Xi repression and demonstrates a central role for RNA in the topological organization of mammalian chromosomes. PMID:26089354

  2. The mechanism of protein kinase C regulation

    Institute of Scientific and Technical Information of China (English)

    Julhash U. KAZI

    2011-01-01

    Protein kinase C (PKC) is a family ofserine/threonine protein kinases that plays a central role in transducing extracellular signals into a variety of intracellular responses ranging from cell proliferation to apoptosis.Nine PKC genes have been identified in the human genome,which encode 10 proteins.Each member of this protein kinase family displays distinct biochemical characteristics and is enriched in different cellular and subcellular locations.Activation of PKC has been implicated in the regulation of cell growth and differentiation.This review summarizes works of the past years in the field of PKC biochemistry that covers regulation and activation mechanism of different PKC isoforms.

  3. Differential AMP-activated Protein Kinase (AMPK) Recognition Mechanism of Ca2+/Calmodulin-dependent Protein Kinase Kinase Isoforms.

    Science.gov (United States)

    Fujiwara, Yuya; Kawaguchi, Yoshinori; Fujimoto, Tomohito; Kanayama, Naoki; Magari, Masaki; Tokumitsu, Hiroshi

    2016-06-24

    Ca(2+)/calmodulin-dependent protein kinase kinase β (CaMKKβ) is a known activating kinase for AMP-activated protein kinase (AMPK). In vitro, CaMKKβ phosphorylates Thr(172) in the AMPKα subunit more efficiently than CaMKKα, with a lower Km (∼2 μm) for AMPK, whereas the CaMKIα phosphorylation efficiencies by both CaMKKs are indistinguishable. Here we found that subdomain VIII of CaMKK is involved in the discrimination of AMPK as a native substrate by measuring the activities of various CaMKKα/CaMKKβ chimera mutants. Site-directed mutagenesis analysis revealed that Leu(358) in CaMKKβ/Ile(322) in CaMKKα confer, at least in part, a distinct recognition of AMPK but not of CaMKIα. PMID:27151216

  4. Chromosomal aberrations in ISS crew members

    Science.gov (United States)

    Johannes, Christian; Goedecke, Wolfgang; Antonopoulos, Alexandra

    2012-07-01

    High energy radiation is a major risk factor in manned space missions. Astronauts and cosmonauts are exposed to ionising radiations of cosmic and solar origin, while on the Earth's surface people are well protected by the atmosphere and a deflecting magnetic field. There are now data available describing the dose and the quality of ionising radiation on-board of the International Space Station (ISS). Nonetheless, the effect of increased radiation dose on mutation rates of ISS crew members are hard to predict. Therefore, direct measurements of mutation rates are required in order to better estimate the radiation risk for longer duration missions. The analysis of chromosomal aberrations in peripheral blood lymphocytes is a well established method to measure radiation-induced mutations. We present data of chromosome aberration analyses from lymphocyte metaphase spreads of ISS crew members participating in short term (10-14 days) or long term (around 6 months) missions. From each subject we received two blood samples. The first sample was drawn about 10 days before launch and a second one within 3 days after return from flight. From lymphocyte cultures metaphase plates were prepared on glass slides. Giemsa stained and in situ hybridised metaphases were scored for chromosome changes in pre-flight and post-flight blood samples and the mutation rates were compared. Results obtained in chromosomal studies on long-term flight crew members showed pronounced inter-individual differences in the response to elevated radiation levels. Overall slight but significant elevations of typical radiation induced aberrations, i.e., dicentric chromosomes and reciprocal translocations have been observed. Our data indicate no elevation of mutation rates due to short term stays on-board the ISS.

  5. Meiotic double-strand breaks at the interface of chromosome movement, chromosome remodeling, and reductional division

    OpenAIRE

    Storlazzi, Aurora; Tessé, Sophie; Gargano, Silvana; James, Françoise; Kleckner, Nancy; Zickler, Denise

    2003-01-01

    Chromosomal processes related to formation and function of meiotic chiasmata have been analyzed in Sordaria macrospora. Double-strand breaks (DSBs), programmed or γ-rays-induced, are found to promote four major events beyond recombination and accompanying synaptonemal complex formation: (1) juxtaposition of homologs from long-distance interactions to close presynaptic coalignment at midleptotene; (2) structural destabilization of chromosomes at leptotene/zygotene, including sister axis separa...

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

    OpenAIRE

    Resim, Sefa; Kadıoğlu, Ateş; Akman, Tolga; Bayrak, Ayşe Gül; Efe, Erkan

    2013-01-01

    Background: Carriers of structural chromosomal rearrangements such as Robertsonian or reciprocal translocations have an increased risk of spontaneous abortion and producing offspring with genetic abnormalities. Case Report: We report a man with balanced chromosomal translocations located at 6p22, and 7q22. His wife has a history of four spontaneous abortions. Conclusion: Couples with a history of abortions should be investigated cytogenetically, after other causes of mis...

  7. Phosphorylation-Independent Regulation of Atf1-Promoted Meiotic Recombination by Stress-Activated, p38 Kinase Spc1 of Fission Yeast

    Science.gov (United States)

    Gao, Jun; Davidson, Mari K.; Wahls, Wayne P.

    2009-01-01

    Background Stress-activated protein kinases regulate multiple cellular responses to a wide variety of intracellular and extracellular conditions. The conserved, multifunctional, ATF/CREB protein Atf1 (Mts1, Gad7) of fission yeast binds to CRE-like (M26) DNA sites. Atf1 is phosphorylated by the conserved, p38-family kinase Spc1 (Sty1, Phh1) and is required for many Spc1-dependent stress responses, efficient sexual differentiation, and activation of Rec12 (Spo11)-dependent meiotic recombination hotspots like ade6-M26. Methodology/Principal Findings We sought to define mechanisms by which Spc1 regulates Atf1 function at the ade6-M26 hotspot. The Spc1 kinase was essential for hotspot activity, but dispensable for basal recombination. Unexpectedly, a protein lacking all eleven MAPK phospho-acceptor sites and detectable phosphorylation (Atf1-11M) was fully proficient for hotspot recombination. Furthermore, tethering of Atf1 to ade6 in the chromosome by a heterologous DNA binding domain bypassed the requirement for Spc1 in promoting recombination. Conclusions/Significance The Spc1 protein kinase regulates the pathway of Atf1-promoted recombination at or before the point where Atf1 binds to chromosomes, and this pathway regulation is independent of the phosphorylation status of Atf1. Since basal recombination is Spc1-independent, the principal function of the Spc1 kinase in meiotic recombination is to correctly position Atf1-promoted recombination at hotspots along chromosomes. We also propose new hypotheses on regulatory mechanisms for shared (e.g., DNA binding) and distinct (e.g., osmoregulatory vs. recombinogenic) activities of multifunctional, stress-activated protein Atf1. PMID:19436749

  8. X-Chromosome Inactivation Counting and Choice: Change or Design

    NARCIS (Netherlands)

    K. Monkhorst (Kim)

    2008-01-01

    textabstractPlacental mammalian female cells have two X chromosomes. One of these chromosomes is randomly inactivated in each nucleus so that females are functionally mosaic for genes expressed from their X chromosomes. The evolutionary basis for this phenomenon is based on the fact that females wou

  9. Autosomal Chromosome Abnormality: A Cause of Birth Defects.

    Science.gov (United States)

    Plumridge, Diane

    Intended for parents and professionals, the book explains chromosome abnormalities in lay terms and discusses the relationship of specific conditions to birth defects. Chromosomal abnormalities are defined and factors in diagnosis and recurrence are discussed. Normal chromosome reproduction processes are covered while such numerical abnormalities…

  10. Chromosome phylogeny of the subfamily Pitheciinae (Platyrrhini, Primates) by classic cytogenetics and chromosome painting

    Science.gov (United States)

    2010-01-01

    Background The New World monkey (Platyrrhini) subfamily Pitheciinae is represented by the genera Pithecia, Chiropotes and Cacajao. In this work we studied the karyotypes of Pithecia irrorata (2n = 48) and Cacajao calvus rubicundus (2n = 45 in males and 2n = 46 in females) by G- and C-banding, NOR staining and chromosome painting using human and Saguinus oedipus whole chromosome probes. The karyotypes of both species were compared with each other and with Chiropotes utahicki (2n = 54) from the literature. Results Our results show that members of the Pitheciinae have conserved several chromosome forms found in the inferred ancestral Platyrrhini karyotype (associations of human homologous segments 3a/21, 5/7a, 2b/16b, 8a/18, 14/15a and 10a/16a). Further, the monophyly of this subfamily is supported by three chromosomal synapomorphies (2a/10b, an acrocentric 15/14 and an acrocentric human 19 homolog). In addition, each species presents several autapomorphies. From this data set we established a chromosomal phylogeny of Pitheciinae, resulting in a single most parsimonious tree. Conclusions In our chromosomal phylogeny, the genus Pithecia occurred in a more basal position close to the inferred ancestor of Platyrrhini, while C. c. rubicundus and C. utahicki are closely related and are linked by exclusive synapomorphies. PMID:20565908

  11. Integrative bacterial artificial chromosomes for DNA integration into the Bacillus subtilis chromosome.

    Science.gov (United States)

    Juhas, Mario; Ajioka, James W

    2016-06-01

    Bacillus subtilis is a well-characterized model bacterium frequently used for a number of biotechnology and synthetic biology applications. Novel strategies combining the advantages of B. subtilis with the DNA assembly and editing tools of Escherichia coli are crucial for B. subtilis engineering efforts. We combined Gibson Assembly and λ red recombineering in E. coli with RecA-mediated homologous recombination in B. subtilis for bacterial artificial chromosome-mediated DNA integration into the well-characterized amyE target locus of the B. subtilis chromosome. The engineered integrative bacterial artificial chromosome iBAC(cav) can accept any DNA fragment for integration into B. subtilis chromosome and allows rapid selection of transformants by B. subtilis-specific antibiotic resistance and the yellow fluorescent protein (mVenus) expression. We used the developed iBAC(cav)-mediated system to integrate 10kb DNA fragment from E. coli K12 MG1655 into B. subtilis chromosome. iBAC(cav)-mediated chromosomal integration approach will facilitate rational design of synthetic biology applications in B. subtilis. PMID:27033694

  12. Independent intrachromosomal recombination events underlie the pericentric inversions of chimpanzee and gorilla chromosomes homologous to human chromosome 16

    OpenAIRE

    Goidts, Violaine; Szamalek, Justyna M.; de Jong, Pieter J; Cooper, David N.; Chuzhanova, Nadia; Hameister, Horst; Kehrer-Sawatzki, Hildegard

    2005-01-01

    Analyses of chromosomal rearrangements that have occurred during the evolution of the hominoids can reveal much about the mutational mechanisms underlying primate chromosome evolution. We characterized the breakpoints of the pericentric inversion of chimpanzee chromosome 18 (PTR XVI), which is homologous to human chromosome 16 (HSA 16). A conserved 23-kb inverted repeat composed of satellites, LINE and Alu elements was identified near the breakpoints and could have mediated the inversion by b...

  13. Estimating Tempo and Mode of Y Chromosome Turnover: Explaining Y Chromosome Loss With the Fragile Y Hypothesis

    OpenAIRE

    Blackmon, Heath; Demuth, Jeffery P.

    2014-01-01

    Chromosomal sex determination is phylogenetically widespread, having arisen independently in many lineages. Decades of theoretical work provide predictions about sex chromosome differentiation that are well supported by observations in both XY and ZW systems. However, the phylogenetic scope of previous work gives us a limited understanding of the pace of sex chromosome gain and loss and why Y or W chromosomes are more often lost in some lineages than others, creating XO or ZO systems. To gain...

  14. Number and size of human X chromosome fragments transferred to mouse cells by chromosome-mediated gene transfer.

    OpenAIRE

    Olsen, A S; McBride, O W; Moore, D. E.

    1981-01-01

    Labeled probes of unique-sequence human X chromosomal deoxyribonucleic acid, prepared by two different procedures, were used to measure the amount of human X chromosomal deoxyribonucleic acid in 12 mouse cell lines expressing human hypoxanthine phosphoribosyltransferase after chromosome-mediated gene transfer. The amount of X chromosomal deoxyribonucleic acid detected by this procedure ranged from undetectable levels in the three stable transformants and some unstable transformants examined t...

  15. Pantothenate kinase-associated neurodegeneration.

    Science.gov (United States)

    Hartig, Monika B; Prokisch, Holger; Meitinger, Thomas; Klopstock, Thomas

    2012-08-01

    Pantothenate kinase-associated neurodegeneration (PKAN) is a hereditary progressive disorder and the most frequent form of neurodegeneration with brain iron accumulation (NBIA). PKAN patients present with a progressive movement disorder, dysarthria, cognitive impairment and retinitis pigmentosa. In magnetic resonance imaging, PKAN patients exhibit the pathognonomic "eye of the tiger" sign in the globus pallidus which corresponds to iron accumulation and gliosis as shown in neuropathological examinations. The discovery of the disease causing mutations in PANK2 has linked the disorder to coenzyme A (CoA) metabolism. PANK2 is the only one out of four PANK genes encoding an isoform which localizes to mitochondria. At least two other NBIA genes (PLA2G6, C19orf12) encode proteins that share with PANK2 a mitochondrial localization and all are suggested to play a role in lipid homeostasis. With no causal therapy available for PKAN until now, only symptomatic treatment is possible. A multi-centre retrospective study with bilateral pallidal deep brain stimulation in patients with NBIA revealed a significant improvement of dystonia. Recently, studies in the PANK Drosophila model "fumble" revealed improvement by the compound pantethine which is hypothesized to feed an alternate CoA biosynthesis pathway. In addition, pilot studies with the iron chelator deferiprone that crosses the blood brain barrier showed a good safety profile and some indication of efficacy. An adequately powered randomized clinical trial will start in 2012. This review summarizes clinical presentation, neuropathology and pathogenesis of PKAN. PMID:22515741

  16. Genetics Home Reference: phosphoglycerate kinase deficiency

    Science.gov (United States)

    ... Children Living with Inherited Metabolic Diseases (CLIMB) (UK) Muscular Dystrophy Association National Organization for Rare Disorders (NORD) Resource list from the University of Kansas Medical Center: Metabolic Conditions Genetic Testing Registry (2 links) Deficiency of phosphoglycerate kinase ...

  17. Genetics Home Reference: mevalonate kinase deficiency

    Science.gov (United States)

    ... net Patient Support and Advocacy Resources (2 links) Autoinflammatory Alliance National Organization for Rare Disorders (NORD): Hyper ... Haas D, Hoffmann GF. Mevalonate kinase deficiency and autoinflammatory disorders. N Engl J Med. 2007 Jun 28; ...

  18. Genetics Home Reference: deoxyguanosine kinase deficiency

    Science.gov (United States)

    ... or mtDNA, which is essential for the normal function of these structures. Deoxyguanosine kinase is involved in producing and maintaining the ... DNA (known as mitochondrial DNA depletion) impairs mitochondrial function ... deficiency . Learn more about the gene associated ...

  19. Kinase inhibitors for advanced medullary thyroid carcinoma

    Directory of Open Access Journals (Sweden)

    Martin Schlumberger

    2012-01-01

    Full Text Available The recent availability of molecular targeted therapies leads to a reconsideration of the treatment strategy for patients with distant metastases from medullary thyroid carcinoma. In patients with progressive disease, treatment with kinase inhibitors should be offered.

  20. Kinome profiling of Arabidopsis using arrays of kinase consensus substrates

    NARCIS (Netherlands)

    Ritsema, T.; Joore, J.; Workum, W. van; Pieterse, C.M.J.

    2007-01-01

    Background: Kinome profiling aims at the parallel analysis of kinase activities in a cell. Novel developed arrays containing consensus substrates for kinases are used to assess those kinase activities. The arrays described in this paper were already used to determine kinase activities in mammalian s

  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. Cross-species chromosome painting tracks the independent origin of multiple sex chromosomes in two cofamiliar Erythrinidae fishes

    Science.gov (United States)

    2011-01-01

    Background The Erythrinidae fish family is characterized by a large variation with respect to diploid chromosome numbers and sex-determining systems among its species, including two multiple X1X2Y sex systems in Hoplias malabaricus and Erythrinus erythrinus. At first, the occurrence of a same sex chromosome system within a family suggests that the sex chromosomes are correlated and originated from ancestral XY chromosomes that were either homomorphic or at an early stage of differentiation. To identify the origin and evolution of these X1X2Y sex chromosomes, we performed reciprocal cross-species FISH experiments with two sex-chromosome-specific probes designed from microdissected X1 and Y chromosomes of H. malabaricus and E. erythrinus, respectively. Results Our results yield valuable information regarding the origin and evolution of these sex chromosome systems. Our data indicate that these sex chromosomes evolved independently in these two closed related Erythrinidae species. Different autosomes were first converted into a poorly differentiated XY sex pair in each species, and additional chromosomal rearrangements produced both X1X2Y sex systems that are currently present. Conclusions Our data provide new insights into the origin and evolution of sex chromosomes, which increases our knowledge about fish sex chromosome evolution. PMID:21718509

  3. The key role of repeated DNAs in sex chromosome evolution in two fish species with ZW sex chromosome system.

    Science.gov (United States)

    de Bello Cioffi, Marcelo; Kejnovský, Eduard; Marquioni, Vinicius; Poltronieri, Juliana; Molina, Wagner Franco; Diniz, Débora; Bertollo, Luiz Antonio Carlos

    2012-01-01

    Despite substantial progress, there are still several gaps in our knowledge about the process of sex chromosome differentiation. The degeneration of sex-specific chromosome in some species is well documented, but it is not clear if all species follow the same evolutionary pathway. The accumulation of repetitive DNA sequences, however, is a common feature. To better understand this involvement, fish species emerge as excellent models because they exhibit a wide variety of sex chromosome and sex determining systems. Besides, they have much younger sex chromosomes compared to higher vertebrates, making it possible to follow early steps of differentiation. Here, we analyzed the arrangement of 9 repetitive DNA sequences in the W chromosomes of 2 fish species, namely Leporinus reinhardti and Triportheus auritus, which present well-differentiated ZZ/ZW sex system, but differ in respect to the size of the sex-specific chromosome. Both W chromosomes are almost fully heterochromatic, with accumulation of repeated DNAs in their heterochromatic regions. We found that microsatellites have strongly accumulated on the large W chromosome of L. reinhardti but not on the reduced-size W chromosome of T. auritus and are therefore important players of the W chromosome expansion. The present data highlight that the evolution of the sex chromosomes can diverge even in the same type of sex system, with and without the degeneration of the specific-sex chromosome, being more dynamic than traditionally appreciated. PMID:22658074

  4. The key role of repeated DNAs in sex chromosome evolution in two fish species with ZW sex chromosome system

    Directory of Open Access Journals (Sweden)

    de Bello Cioffi Marcelo

    2012-06-01

    Full Text Available Abstract Despite substantial progress, there are still several gaps in our knowledge about the process of sex chromosome differentiation. The degeneration of sex-specific chromosome in some species is well documented, but it is not clear if all species follow the same evolutionary pathway. The accumulation of repetitive DNA sequences, however, is a common feature. To better understand this involvement, fish species emerge as excellent models because they exhibit a wide variety of sex chromosome and sex determining systems. Besides, they have much younger sex chromosomes compared to higher vertebrates, making it possible to follow early steps of differentiation. Here, we analyzed the arrangement of 9 repetitive DNA sequences in the W chromosomes of 2 fish species, namely Leporinus reinhardti and Triportheus auritus, which present well-differentiated ZZ/ZW sex system, but differ in respect to the size of the sex-specific chromosome. Both W chromosomes are almost fully heterochromatic, with accumulation of repeated DNAs in their heterochromatic regions. We found that microsatellites have strongly accumulated on the large W chromosome of L. reinhardti but not on the reduced-size W chromosome of T. auritus and are therefore important players of the W chromosome expansion. The present data highlight that the evolution of the sex chromosomes can diverge even in the same type of sex system, with and without the degeneration of the specific-sex chromosome, being more dynamic than traditionally appreciated.

  5. A Study on the Chromosomes of Konya Wild Sheep (Ovis orientalis spp.): Case Report

    OpenAIRE

    KIRIKÇI, Kemal

    2003-01-01

    We investigated the shape and number of chromosomes of Konya wild sheep. A karyotype was prepared from G-band painted chromosomes. Konya wild sheep have 54 diploid chromosomes. The first three autosomal chromosomes were metacentric, and the other autosomal chromosomes and X chromosomes were acrocentric.

  6. The Ca2+/Calmodulin-Dependent Protein Kinase Kinase, CaMKK2, Inhibits Preadipocyte Differentiation

    OpenAIRE

    Lin, Fumin; Ribar, Thomas J.; Means, Anthony R.

    2011-01-01

    When fed a standard chow diet, CaMKK2 null mice have increased adiposity and larger adipocytes than do wild-type mice, whereas energy balance is unchanged. Here, we show that Ca2+/calmodulin-dependent protein kinase kinase 2 (CaMKK2) is expressed in preadipocytes, where it functions as an AMP-activated protein kinase (AMPK)α kinase. Acute inhibition or deletion of CaMKK2 in preadipocytes enhances their differentiation into mature adipocytes, which can be reversed by 5-aminoimidazole-4-carboxa...

  7. Protein kinase domain of twitchin has protein kinase activity and an autoinhibitory region.

    Science.gov (United States)

    Lei, J; Tang, X; Chambers, T C; Pohl, J; Benian, G M

    1994-08-19

    Twitchin is a 753-kDa polypeptide located in the muscle A-bands of the nematode, Caenorhabditis elegans. It consists of multiple copies of both fibronectin III and immunoglobulin C2 domains and, near the C terminus, a protein kinase domain with greatest homology to the catalytic domains of myosin light chain kinases. We have expressed and purified from Escherichia coli twitchin's protein kinase catalytic core and flanking sequences that do not include fibronectin III and immunoglobulin C2 domains. The protein was shown to phosphorylate a model substrate and to undergo autophosphorylation. The autophosphorylation occurs at a slow rate, attaining a maximum at 3 h with a stoichiometry of about 1.0 mol of phosphate/mol of protein, probably through an intramolecular mechanism. Sequence analysis of proteolytically derived phosphopeptides revealed that autophosphorylation occurred N-terminal to the catalytic core, predominantly at Thr-5910, with possible minor sites at Ser5912 and/or Ser-5913. This portion of twitchin (residues 5890-6268) was also phosphorylated in vitro by protein kinase C in the absence of calcium and phosphotidylserine, but not by cAMP-dependent protein kinase. By comparing the activities of three twitchin segments, the enzyme appears to be inhibited by the 60-amino acid residues lying just C-terminal to the kinase catalytic core. Thus, like a number of other protein kinases including myosin light chain kinases, the twitchin kinase appears to be autoregulated. PMID:8063727

  8. Seeding collaborations to advance kinase science with the GSK Published Kinase Inhibitor Set (PKIS).

    Science.gov (United States)

    Drewry, David H; Willson, Timothy M; Zuercher, William J

    2014-01-01

    To catalyze research on historically untargeted protein kinases, we created the PKIS, an annotated set of 367 small molecule kinase inhibitors. The set has been widely distributed to academic collaborators as an open access tool. It has been used to identify chemical starting points for development of chemical probes for orphan kinases and to investigate kinase signaling in high content phenotypic assays. Access to the set comes with few restrictions other than the requirement that assay results be released into the public domain for the benefit of the entire research community. Examples from the efforts of several collaborators are summarized. PMID:24283969

  9. Janus kinases in immune cell signaling

    OpenAIRE

    Ghoreschi, Kamran; Laurence, Arian; O’Shea, John J.

    2009-01-01

    The Janus family kinases (Jaks), Jak1, Jak2, Jak3, and Tyk2, form one subgroup of the non-receptor protein tyrosine kinases. They are involved in cell growth, survival, development, and differentiation of a variety of cells but are critically important for immune cells and hematopoietic cells. Data from experimental mice and clinical observations have unraveled multiple signaling events mediated by Jak in innate and adaptive immunity. Deficiency of Jak3 or Tyk2 results in defined clinical dis...

  10. Non-degradative Ubiquitination of Protein Kinases.

    OpenAIRE

    K Aurelia Ball; Johnson, Jeffrey R.; Lewinski, Mary K; John Guatelli; Erik Verschueren; Krogan, Nevan J.; Matthew P Jacobson

    2016-01-01

    Growing evidence supports other regulatory roles for protein ubiquitination in addition to serving as a tag for proteasomal degradation. In contrast to other common post-translational modifications, such as phosphorylation, little is known about how non-degradative ubiquitination modulates protein structure, dynamics, and function. Due to the wealth of knowledge concerning protein kinase structure and regulation, we examined kinase ubiquitination using ubiquitin remnant immunoaffinity enrichm...

  11. Chromosome mapping of repetitive sequences in Anostomidae species: implications for genomic and sex chromosome evolution

    Directory of Open Access Journals (Sweden)

    da Silva Edson Lourenço

    2012-12-01

    Full Text Available Abstract Background Members of the Anostomidae family provide an interesting model system for the study of the influence of repetitive elements on genome composition, mainly because they possess numerous heterochromatic segments and a peculiar system of female heterogamety that is restricted to a few species of the Leporinus genus. The aim of this study was to isolate and identify important new repetitive DNA elements in Anostomidae through restriction enzyme digestion, followed by cloning, characterisation and chromosome mapping of this fragment. To identify repetitive elements in other Leporinus species and expand on studies of repetitive elements in Anostomidae, hybridisation experiments were also performed using previously described probes of LeSpeI repetitive elements. Results The 628-base pair (bp LeSpeII fragment was hybridised to metaphase cells of L. elongatus individuals as well as those of L. macrocephalus, L. obtusidens, L. striatus, L. lacustris, L. friderici, Schizodon borellii and S. isognathus. In L. elongatus, both male and female cells contained small clusters of LeSpeII repetitive elements dispersed on all of the chromosomes, with enrichment near most of the terminal portions of the chromosomes. In the female sex chromosomes of L. elongatus (Z2,Z2/W1W2, however, this repeated element was absent. In the remaining species, a dispersed pattern of hybridisation was observed on all chromosomes irrespective of whether or not they were sex chromosomes. The repetitive element LeSpeI produced positive hybridisations signals only in L. elongatus, L. macrocephalus and L. obtusidens, i.e., species with differentiated sex chromosomes. In the remaining species, the LeSpeI element did not produce hybridisation signals. Conclusions Results are discussed in terms of the effects of repetitive sequences on the differentiation of the Anostomidae genome, especially with respect to sex chromosome evolution. LeSpeII showed hybridisation patterns

  12. Chromosome localization analysis of genes strongly expressed in human visceral adipose tissue.

    Science.gov (United States)

    Yang, Yi-Sheng; Song, Huai-Dong; Shi, Wen-Jing; Hu, Ren-Ming; Han, Ze-Guang; Chen, Jia-Lun

    2002-06-01

    To understand fully the physiologic functions of visceral adipose tissue and to provide a basis for the identification of novel genes related to obesity and insulin resistance, the gene expression profiling of human visceral adipose tissue was established by using cDNA array. The characterization and chromosome localization of 400 expressed sequence tags (ESTs) strongly expressed in visceral adipose tissue were analyzed by searching PubMed, UniGene, the Human Genome Draft Database, and Location Data Base. Two hundred eighty-nine clones were classified into known genes among the 400 ESTs strongly expressed in the tissue. Among them, proteina; and phosphoinositide-3-kinase, regulatory subunit, polypeptide 2 (p85beta), were also localized in the concentrated regions, which may provide clues to identifying novel genes closely related to adipocyte function with potential pathophysiologic implications. PMID:12166625

  13. Chromosome-Specific Painting in Cucumis Species Using Bulked Oligonucleotides.

    Science.gov (United States)

    Han, Yonghua; Zhang, Tao; Thammapichai, Paradee; Weng, Yiqun; Jiang, Jiming

    2015-07-01

    Chromosome-specific painting is a powerful technique in molecular cytogenetic and genome research. We developed an oligonucleotide (oligo)-based chromosome painting technique in cucumber (Cucumis sativus) that will be applicable in any plant species with a sequenced genome. Oligos specific to a single chromosome of cucumber were identified using a newly developed bioinformatic pipeline and then massively synthesized de novo in parallel. The synthesized oligos were amplified and labeled with biotin or digoxigenin for use in fluorescence in situ hybridization (FISH). We developed three different probes with each containing 23,000-27,000 oligos. These probes spanned 8.3-17 Mb of DNA on targeted cucumber chromosomes and had the densities of 1.5-3.2 oligos per kilobases. These probes produced FISH signals on a single cucumber chromosome and were used to paint homeologous chromosomes in other Cucumis species diverged from cucumber for up to 12 million years. The bulked oligo probes allowed us to track a single chromosome in early stages during meiosis. We were able to precisely map the pairing between cucumber chromosome 7 and chromosome 1 of Cucumis hystrix in a F1 hybrid. These two homeologous chromosomes paired in 71% of prophase I cells but only 25% of metaphase I cells, which may provide an explanation of the higher recombination rates compared to the chiasma frequencies between homeologous chromosomes reported in plant hybrids. PMID:25971668

  14. DNA immunization with a herpes simplex virus 2 bacterial artificial chromosome

    International Nuclear Information System (INIS)

    Construction of a herpes simplex virus 2 (HSV-2) bacterial artificial chromosome (BAC) is described. BAC vector sequences were inserted into the thymidine kinase gene of HSV-2 by homologous recombination. DNA from cells infected with the resulting recombinant virus was transformed into E. coli, and colonies containing the HSV-2 BAC (HSV2-BAC) were isolated and analyzed for the expected genotype. HSV2-BAC DNA was infectious when transfected back into mammalian cells and the resulting virus was thymidine kinase negative. When used to immunize mice, the HSV2-BAC DNA elicited a strong HSV-2 specific antibody response that was equal to or greater than live virus immunization. Further, HSV2-BAC immunization was protective when animals were challenged with a lethal dose of virus. The utility of the HSV2-BAC for construction of recombinant virus genomes was demonstrated by elimination of the HSV-2 glycoprotein D (gD) gene. A recombinant HSV-2 BAC with the gD gene deleted was isolated and shown to be incapable of producing infectious virus following transfection unless an HSV gD gene was expressed in a complementing cell line. Immunization of mice with the HSV2 gD-BAC also elicited an HSV-2 specific antibody response and was protective. The results demonstrate the feasibility of DNA immunization with HSV-2 bacterial artificial chromosomes for replicating and nonreplicating candidate HSV-2 vaccines, as well as the utility of BAC technology for construction and maintenance of novel HSV-2 vaccines. The results further suggest that such technology will be a powerful tool for dissecting the immune response to HSV-2

  15. Evolutionary Reconstruction and Population Genetics Analysis of Aurora Kinases

    OpenAIRE

    Balu Kamaraj; Ambuj Kumar; Rituraj Purohit

    2013-01-01

    BACKGROUND: Aurora kinases belong to the highly conserved kinase family and play a vital role in cell cycle regulation. The structure and function of these kinases are inter-related and sometimes they also act as substitutes in case of knockdown of other aurora kinases. METHOD: In this work we carried out the evolutionary reconstruction and population genetic studies of aurora kinase proteins. Substitution saturation test, CAI (Codon adaptation index), gene expression and RSCU (Relative synon...

  16. DNA sequence and analysis of human chromosome 18.

    Science.gov (United States)

    Nusbaum, Chad; Zody, Michael C; Borowsky, Mark L; Kamal, Michael; Kodira, Chinnappa D; Taylor, Todd D; Whittaker, Charles A; Chang, Jean L; Cuomo, Christina A; Dewar, Ken; FitzGerald, Michael G; Yang, Xiaoping; Abouelleil, Amr; Allen, Nicole R; Anderson, Scott; Bloom, Toby; Bugalter, Boris; Butler, Jonathan; Cook, April; DeCaprio, David; Engels, Reinhard; Garber, Manuel; Gnirke, Andreas; Hafez, Nabil; Hall, Jennifer L; Norman, Catherine Hosage; Itoh, Takehiko; Jaffe, David B; Kuroki, Yoko; Lehoczky, Jessica; Lui, Annie; Macdonald, Pendexter; Mauceli, Evan; Mikkelsen, Tarjei S; Naylor, Jerome W; Nicol, Robert; Nguyen, Cindy; Noguchi, Hideki; O'Leary, Sinéad B; O'Neill, Keith; Piqani, Bruno; Smith, Cherylyn L; Talamas, Jessica A; Topham, Kerri; Totoki, Yasushi; Toyoda, Atsushi; Wain, Hester M; Young, Sarah K; Zeng, Qiandong; Zimmer, Andrew R; Fujiyama, Asao; Hattori, Masahira; Birren, Bruce W; Sakaki, Yoshiyuki; Lander, Eric S

    2005-09-22

    Chromosome 18 appears to have the lowest gene density of any human chromosome and is one of only three chromosomes for which trisomic individuals survive to term. There are also a number of genetic disorders stemming from chromosome 18 trisomy and aneuploidy. Here we report the finished sequence and gene annotation of human chromosome 18, which will allow a better understanding of the normal and disease biology of this chromosome. Despite the low density of protein-coding genes on chromosome 18, we find that the proportion of non-protein-coding sequences evolutionarily conserved among mammals is close to the genome-wide average. Extending this analysis to the entire human genome, we find that the density of conserved non-protein-coding sequences is largely uncorrelated with gene density. This has important implications for the nature and roles of non-protein-coding sequence elements. PMID:16177791

  17. X Chromosome and Autosome Dosage Responses in Drosophila melanogaster Heads.

    Science.gov (United States)

    Chen, Zhen-Xia; Oliver, Brian

    2015-06-01

    X chromosome dosage compensation is required for male viability in Drosophila. Dosage compensation relative to autosomes is two-fold, but this is likely to be due to a combination of homeostatic gene-by-gene regulation and chromosome-wide regulation. We have baseline values for gene-by-gene dosage compensation on autosomes, but not for the X chromosome. Given the evolutionary history of sex chromosomes, these baseline values could differ. We used a series of deficiencies on the X and autosomes, along with mutations in the sex-determination gene transformer-2, to carefully measure the sex-independent X-chromosome response to gene dosage in adult heads by RNA sequencing. We observed modest and indistinguishable dosage compensation for both X chromosome and autosome genes, suggesting that the X chromosome is neither inherently more robust nor sensitive to dosage change. PMID:25850426

  18. Transmission Behavior of B Chromosomes in Prochilodus lineatus (Characiformes, Prochilodontidae).

    Science.gov (United States)

    Penitente, Manolo; Daniel, Sandro N; Senhorini, José A; Foresti, Fausto; Porto-Foresti, Fábio

    2015-01-01

    The population of Prochilodus lineatus found in the Mogi-Guaçu River is karyotypically polymorphic, carrying acrocentric, metacentric, and submetacentric B chromosomes. The analysis of each B chromosome frequency in this species revealed a variation in the distribution pattern, with the metacentric type having the highest frequency (73.30%), followed by submetacentric (25.22%) and acrocentric B chromosomes (1.48%). The transmission pattern of the supernumerary chromosomes was identified by controlled crosses, and it was shown that the acro- and submetacentric B chromosomes have a transmission pattern below the Mendelian rate (kB = 0.333 and kB = 0.385, respectively), but the metacentric variant has a cumulative transmission pattern (kB = 0.587). These results indicate that the acro- and submetacentric B chromosomes are undergoing an extinction process, while the metacentric B chromosomes appear to be accumulating in frequency with each generation. PMID:26795613

  19. Bacillus subtilis strain deficient for the protein-tyrosine kinase PtkA exhibits impaired DNA replication

    DEFF Research Database (Denmark)

    Petranovic, Dina; Michelsen, Ole; Zahradka, K;

    2007-01-01

    study. We were unable to identify any striking phenotypes related to control of UDP-glucose dehydrogenases, natural competence and DNA lesion repair; however, a very strong phenotype of ΔptkA emerged with respect to DNA replication and cell cycle control, as revealed by flow cytometry and fluorescent...... microscopy. B. subtilis cells lacking the kinase PtkA accumulated extra chromosome equivalents, exhibited aberrant initiation mass for DNA replication and an unusually long D period....... previously shown to regulate the phosphorylation state of UDP-glucose dehydrogenases and single-stranded DNA-binding proteins. This promiscuity towards substrates is reminiscent of eukaryal kinases and has prompted us to investigate possible physiological effects of ptkA and ptpZ gene inactivations in this...

  20. A pathway containing the Ipl1/Aurora protein kinase and the spindle midzone protein Ase1 regulates yeast spindle assembly

    OpenAIRE

    Kotwaliwale, Chitra V.; Frei, Stéphanie Buvelot; Stern, Bodo M.; Biggins, Sue

    2007-01-01

    It is critical to elucidate the pathways that mediate spindle assembly and therefore ensure accurate chromosome segregation during cell division. Our studies of a unique allele of the budding yeast Ipl1/Aurora protein kinase revealed that it is required for centrosome-mediated spindle assembly in the absence of the BimC motor protein Cin8. In addition, we found that the Ase1 spindle midzone-associated protein is required for bipolar spindle assembly. The cin8 ipl1 and cin8 ase1 double mutant ...

  1. Chronic Myeloid Leukemia in the Era of Tyrosine Kinase Inhibitors: An Evolving Paradigm of Molecularly Targeted Therapy.

    Science.gov (United States)

    Ali, Mohamed A M

    2016-08-01

    Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm, characterized by the unrestrained expansion of pluripotent hematopoietic stem cells. CML was the first malignancy in which a unique chromosomal abnormality was identified and a pathophysiologic association was suggested. The hallmark of CML is a reciprocal chromosomal translocation between the long arms of chromosomes 9 and 22, t(9; 22)(q34; q11), creating a derivative 9q+ and a shortened 22q-. The latter, known as the Philadelphia (Ph) chromosome, harbors the breakpoint cluster region-abelson (BCR-ABL) fusion gene, encoding the constitutively active BCR-ABL tyrosine kinase that is necessary and sufficient for initiating CML. The successful implementation of tyrosine kinase inhibitors (TKIs) for the treatment of CML remains a flagship for molecularly targeted therapy in cancer. TKIs have changed the clinical course of CML; however, some patients nonetheless demonstrate primary or secondary resistance to such therapy and require an alternative therapeutic strategy. Therefore, the assessment of early response to treatment with TKIs has become an important tool in the clinical monitoring of CML patients. Although mutations in the BCR-ABL have proven to be the most prominent mechanism of resistance to TKIs, other mechanisms-either rendering the leukemic cells still dependent on BCR-ABL activity or supporting oncogenic properties of the leukemic cells independent of BCR-ABL signaling-have been identified. This article provides an overview of the current understanding of CML pathogenesis; recommendations for diagnostic tools, treatment strategies, and management guidelines; and highlights the BCR-ABL-dependent and -independent mechanisms that contribute to the development of resistance to TKIs. PMID:27220498

  2. Antibodies against chromosomal beta-lactamase

    DEFF Research Database (Denmark)

    Giwercman, B; Rasmussen, J W; Ciofu, Oana; Clemmentsen, I; Schumacher, H; Høiby, N

    1994-01-01

    A murine monoclonal anti-chromosomal beta-lactamase antibody was developed and an immunoblotting technique was used to study the presence of serum and sputum antibodies against Pseudomonas aeruginosa chromosomal group 1 beta-lactamase in patients with cystic fibrosis (CF). The serum antibody...... response was studied with serum samples collected in 1992 from 56 CF patients in a cross-sectional study and with serum samples from 18 CF patients in a longitudinal study. Anti-beta-lactamase immunoglobulin G antibodies were present in all of the serum samples from the patients with chronic...... bronchopulmonary P. aeruginosa infection (CF + P) but in none of the CF patients with no or intermittent P. aeruginosa infection. Anti-beta-lactamase antibodies were present in serum from CF + P patients after six antipseudomonal courses (median) and correlated with infection with a beta-lactam-resistant strain of...

  3. Chromosome-based genomics in cereals

    Czech Academy of Sciences Publication Activity Database

    Doležel, Jaroslav; Kubaláková, Marie; Paux, E.; Bartoš, Jan; Feuillet, C.

    2007-01-01

    Roč. 15, č. 1 (2007), s. 51-66. ISSN 0967-3849 R&D Projects: GA ČR GP521/06/P412; GA ČR(CZ) GA521/05/0257; GA ČR GA521/06/1723; GA MŠk ME 884; GA MŠk(CZ) LC06004 Institutional research plan: CEZ:AV0Z50380511 Source of funding: V - iné verejné zdroje ; V - iné verejné zdroje ; V - iné verejné zdroje ; V - iné verejné zdroje ; V - iné verejné zdroje Keywords : Chromosome sorting * chromosome-specific BAC libraries * flow cytometry Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.469, year: 2007

  4. Bacterial Artificial Chromosome Mutagenesis Using Recombineering

    Directory of Open Access Journals (Sweden)

    Kumaran Narayanan

    2011-01-01

    Full Text Available Gene expression from bacterial artificial chromosome (BAC clones has been demonstrated to facilitate physiologically relevant levels compared to viral and nonviral cDNA vectors. BACs are large enough to transfer intact genes in their native chromosomal setting together with flanking regulatory elements to provide all the signals for correct spatiotemporal gene expression. Until recently, the use of BACs for functional studies has been limited because their large size has inherently presented a major obstacle for introducing modifications using conventional genetic engineering strategies. The development of in vivo homologous recombination strategies based on recombineering in E. coli has helped resolve this problem by enabling facile engineering of high molecular weight BAC DNA without dependence on suitably placed restriction enzymes or cloning steps. These techniques have considerably expanded the possibilities for studying functional genetics using BACs in vitro and in vivo.

  5. Evolutionarily conserved sequences on human chromosome 21

    Energy Technology Data Exchange (ETDEWEB)

    Frazer, Kelly A.; Sheehan, John B.; Stokowski, Renee P.; Chen, Xiyin; Hosseini, Roya; Cheng, Jan-Fang; Fodor, Stephen P.A.; Cox, David R.; Patil, Nila

    2001-09-01

    Comparison of human sequences with the DNA of other mammals is an excellent means of identifying functional elements in the human genome. Here we describe the utility of high-density oligonucleotide arrays as a rapid approach for comparing human sequences with the DNA of multiple species whose sequences are not presently available. High-density arrays representing approximately 22.5 Mb of nonrepetitive human chromosome 21 sequence were synthesized and then hybridized with mouse and dog DNA to identify sequences conserved between humans and mice (human-mouse elements) and between humans and dogs (human-dog elements). Our data show that sequence comparison of multiple species provides a powerful empiric method for identifying actively conserved elements in the human genome. A large fraction of these evolutionarily conserved elements are present in regions on chromosome 21 that do not encode known genes.

  6. Survey of human chromosomal abnormalities in Iceland

    Energy Technology Data Exchange (ETDEWEB)

    Jensson, O.; Hauksdottir, H.; Bjarnason, O.; Tulinius, H.

    1976-06-01

    The work of the Chromosome Laboratory of the Genetical Committee of the University of Iceland is reviewed. Initially, the main aim was to carry out cytogenetic typing of all individuals in Iceland with Down's syndrome available for study in institutions and homes, including individuals born in maternity clinics and homes during the eight years of investigation. The results of the chromosome investigation are summarized in Table 1. Lymphocyte cultures were made from a total of 932 individuals from September 1967 to 1975 and 152 individuals with Down's syndrome were cytogenetically typed. Unusual karyotype leading to Down's syndrome was found in 10 cases. Of these six were found to be mosaic, two had D/G and two G/G translocation. By cytogenetic family survey 13 D/G translocation carriers were detected in the family. A separate paper on the cytogenetic survey of Down's syndrome in Iceland is under way.

  7. Chromosome heteromorphisms in the Japanese, 1

    International Nuclear Information System (INIS)

    Thirty-four cases with Dp+ and Gp+, known to be chromosome heteromorphisms in man, were examined using Q- and C-staining methods. Of 18 cases with Dp+, 14 involved No. 15 chromosome and 2 each were No. 13 and No. 14 respectively. Of 16 cases with Gp+, 13 were concerned with No. 22 and the remaining 3 were No. 21. Short arm regions of eight cases with 15p+ and one with 14p+ were stained very darkly by the C-method, but did not fluoresce brilliantly by the Q-method. On the other hand, brightly fluorescing short arm regions observed in three cases with 15p+ and two with 22p+, were not very darkly stained by the C-method. In the remaining 20 cases, short arm regions were not stained positively by either method, but showed negatively or intermediately variable staining intensities. (author)

  8. American marsupials chromosomes: why study them?

    Directory of Open Access Journals (Sweden)

    Marta Svartman

    2009-01-01

    Full Text Available Marsupials, one of the three main groups of mammals, are only found in Australia and in the American continent. Studies performed in Australian marsupials have demonstrated the great potential provided by the group for the understanding of basic genetic mechanisms and chromosome evolution in mammals. Genetic studies in American marsupials are relatively scarce and cytogenetic data of most species are restricted to karyotype descriptions, usually without banding patterns. Nevertheless, the first marsupial genome sequenced was that of Monodelphis domestica, a South American species. The knowledge about mammalian genome evolution and function that resulted from studies on M. domestica is in sharp contrast with the lack of genetic data on most American marsupial species. Here, we present an overview of the chromosome studies performed in marsupials with emphasis on the South American species.

  9. Genome size, karyotype polymorphism and chromosomal evolution in Trypanosoma cruzi.

    Directory of Open Access Journals (Sweden)

    Renata T Souza

    Full Text Available BACKGROUND: The Trypanosoma cruzi genome was sequenced from a hybrid strain (CL Brener. However, high allelic variation and the repetitive nature of the genome have prevented the complete linear sequence of chromosomes being determined. Determining the full complement of chromosomes and establishing syntenic groups will be important in defining the structure of T. cruzi chromosomes. A large amount of information is now available for T. cruzi and Trypanosoma brucei, providing the opportunity to compare and describe the overall patterns of chromosomal evolution in these parasites. METHODOLOGY/PRINCIPAL FINDINGS: The genome sizes, repetitive DNA contents, and the numbers and sizes of chromosomes of nine strains of T. cruzi from four lineages (TcI, TcII, TcV and TcVI were determined. The genome of the TcI group was statistically smaller than other lineages, with the exception of the TcI isolate Tc1161 (José-IMT. Satellite DNA content was correlated with genome size for all isolates, but this was not accompanied by simultaneous amplification of retrotransposons. Regardless of chromosomal polymorphism, large syntenic groups are conserved among T. cruzi lineages. Duplicated chromosome-sized regions were identified and could be retained as paralogous loci, increasing the dosage of several genes. By comparing T. cruzi and T. brucei chromosomes, homologous chromosomal regions in T. brucei were identified. Chromosomes Tb9 and Tb11 of T. brucei share regions of syntenic homology with three and six T. cruzi chromosomal bands, respectively. CONCLUSIONS: Despite genome size variation and karyotype polymorphism, T. cruzi lineages exhibit conservation of chromosome structure. Several syntenic groups are conserved among all isolates analyzed in this study. The syntenic regions are larger than expected if rearrangements occur randomly, suggesting that they are conserved owing to positive selection. Mapping of the syntenic regions on T. cruzi chromosomal bands

  10. Genomic regulatory landscapes and chromosomal rearrangements

    DEFF Research Database (Denmark)

    Ladegaard, Elisabete L Engenheiro

    2008-01-01

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

  11. Chromosomal aberrations and bone marrow toxicity.

    OpenAIRE

    Heddle, J A; Salamone, M F

    1981-01-01

    The importance of chromosomal aberrations as a proximate cause of bone marrow toxicity is discussed. Since chemicals that can cause nondisjunction are rare, numerical aberrations (aneuploidy, polyploidy) are not ordinarily important. Many structural aberrations, however, can lead directly to cell death and so are proximate causes of toxicity when they occur. The micronucleus test which utilizes the polychromatic erythrocyte is capable of detecting agents (clastogens) that can cause such struc...

  12. American marsupials chromosomes: Why study them?

    OpenAIRE

    Marta Svartman

    2009-01-01

    Marsupials, one of the three main groups of mammals, are only found in Australia and in the American continent. Studies performed in Australian marsupials have demonstrated the great potential provided by the group for the understanding of basic genetic mechanisms and chromosome evolution in mammals. Genetic studies in American marsupials are relatively scarce and cytogenetic data of most species are restricted to karyotype descriptions, usually without banding patterns. Nevertheless, the fir...

  13. Chromosomal evolution in Rattini (Muridae, Rodentia)

    OpenAIRE

    Badenhorst, Daleen; Dobigny, Gauthier; Adega, Filomena; Chaves, Raquel; O’Brien, Patricia C. M.; Ferguson-Smith, Malcolm A; Waters, Paul D.; Robinson, Terence J

    2011-01-01

    The Rattini (Muridae, Murinae) includes the biologically important model species Rattus norvegicus (RNO) and represents a group of rodents that are of clinical, agricultural and epidemiological importance. We present a comparative molecular cytogenetic investigation of ten Rattini species representative of the genera Maxomys, Leopoldamys, Niviventer, Berylmys, Bandicota and Rattus using chromosome banding, cross-species painting (Zoo-fluorescent in situ hybridization or FISH) and BAC-FISH map...

  14. Chromosomal instability determines taxane sensitivity - supplementary materials

    OpenAIRE

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

    2009-01-01

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

  15. Y-chromosome STR haplotypes in Somalis

    DEFF Research Database (Denmark)

    Hallenberg, Charlotte; Simonsen, Bo; Sanchez Sanchez, Juan Jose;

    2005-01-01

    A total of 201 males from Somalia were typed for the Y-chromosome STRs DYS19, DYS385a/b, DYS389-I, DYS389-II, DYS390, DYS391, DYS392, DYS393, DYS437, DYS438 and DYS439 with the PowerPlex Y kit (Promega). A total of 96 different haplotypes were observed and the haplotype diversity was 0.9715. The...

  16. Evolution of Y chromosome gene functions

    Czech Academy of Sciences Publication Activity Database

    Žlůvová, Jitka; Marková, Michaela; Janoušek, Bohuslav; Vyskot, Boris

    Marseilles, 2006. s. 19-19. [10th Evolution ary Biology Meeting at Marseilles. 20.09.2006-22.09.2006, Marseilles] R&D Projects: GA ČR(CZ) GP204/05/P505; GA ČR(CZ) GD205/05/H505 Institutional research plan: CEZ:AV0Z50040507 Keywords : Silene latifolia * Y chromosome Subject RIV: BO - Biophysics

  17. Chromosomal radiosensitivity in common variable immune deficiency

    Energy Technology Data Exchange (ETDEWEB)

    Vorechovsky, Igor (Karolinska Institute, Center for BioTechnology, Huddinge (Sweden)); Scott, David (Cancer Research Campaign Department of Cancer Genetics, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester (United Kingdom)); Haeney, Mansel R. (Department of Immunology, Hope Hospital, Salford (United Kingdom)); Webster, David A.B. (Clinical Research Centre, Northwick Park Hospital, Harrow, Middlesex (United Kingdom))

    1993-12-01

    From more than 500 tumours reported in human primary immune deficiencies a majority has been observed in two disorders: ataxia telangiectasia (A-T) and common variable immune deficiency (CVID). Since both diseases have an increased risk of lymphomas/leukaemias and gastrointestinal tumours, suggesting a common risk factor, and the cells derived from A-T patients exhibit an increased chromosomal radiosensitivity we analysed chromosome damage in the G[sub 2] lymphocytes of 24 CVID patients and 21 controls after X-irradiation in vitro. There was a significant difference in mean aberration yields between patients and controls. Three CVID patients had yields higher than the mean+3SD of the controls. Six patients but only one control had yields higher than the mean+2SD of controls. The patient with the highest chromosomal radiosensitivity subsequently developed a lymphoma. Repeat assays on the same blood sample, with a 24-h delay in setting up the second culture, showed as much variability for control donors as the variation between control donors although for CVID patients inter-individual variation was greater than the difference between results of repeat samples. There was a weak positive correlation between radiosensitivity and age of donor. Chromosomal radiosensitivity of five patients with X-linked hypogammaglobulinaemia was not different from healthy donors. The mean mitotic index (MI) for unirradiated samples from CVID patients was significantly lower than for controls and there was an inverse relationship between MI and aberration yields in the patients, but not in controls. We suggest that the defect in CVID patients that reduces response to mitogenic stimuli may have mechanism(s) in common with those involved in cellular repair processes.

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

    Science.gov (United States)

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

    2013-11-01

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

  19. Autism and chromosome abnormalities-A review.

    Science.gov (United States)

    Bergbaum, Anne; Ogilvie, Caroline Mackie

    2016-07-01

    The neuro-behavioral disorder of autism was first described in the 1940s and was predicted to have a biological basis. Since that time, with the growth of genetic investigations particularly in the area of pediatric development, an increasing number of children with autism and related disorders (autistic spectrum disorders, ASD) have been the subject of genetic studies both in the clinical setting and in the wider research environment. However, a full understanding of the biological basis of ASDs has yet to be achieved. Early observations of children with chromosomal abnormalities detected by G-banded chromosome analysis (karyotyping) and in situ hybridization revealed, in some cases, ASD associated with other features arising from such an abnormality. The introduction of higher resolution techniques for whole genome screening, such as array comparative genome hybridization (aCGH), allowed smaller imbalances to be detected, some of which are now considered to represent autism susceptibility loci. In this review, we describe some of the work underpinning the conclusion that ASDs have a genetic basis; a brief history of the developments in genetic analysis tools over the last 50 years; and the most common chromosome abnormalities found in association with ASDs. Introduction of next generation sequencing (NGS) into the clinical diagnostic setting is likely to provide further insights into this complex field but will not be covered in this review. Clin. Anat. 29:620-627, 2016. © 2016 Wiley Periodicals, Inc. PMID:27012322

  20. 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

  1. Chromosome evolution in dendropsophini (Amphibia, Anura, Hylinae).

    Science.gov (United States)

    Suárez, P; Cardozo, D; Baldo, D; Pereyra, M O; Faivovich, J; Orrico, V G D; Catroli, G F; Grabiele, M; Bernarde, P S; Nagamachi, C Y; Haddad, C F B; Pieczarka, J C

    2013-01-01

    Dendropsophini is the most species-rich tribe within Hylidae with 234 described species. Although cytogenetic information is sparse, chromosome numbers and morphology have been considered as an important character system for systematic inferences in this group. Using a diversity of standard and molecular techniques, we describe the previously unknown karyotypes of the genera Xenohyla, Scarthyla and Sphaenorhynchus and provide new information on Dendropsophus and Lysapsus. Our results reveal significant karyotype diversity among Dendropsophini, with diploid chromosome numbers ranging from 2n = 22 in S. goinorum, 2n = 24 in Lysapsus, Scinax, Xenohyla, and almost all species of Sphaenorhynchus and Pseudis, 2n = 26 in S. carneus, 2n = 28 in P. cardosoi, to 2n = 30 in all known Dendropsophus species. Although nucleolar organizer regions (NORs) and C-banding patterns show a high degree of variability, NOR positions in 2n = 22, 24 and 28 karyotypes and C-banding patterns in Lysapsus and Pseudis are informative cytological markers. Interstitial telomeric sequences reveal a diploid number reduction from 24 to 22 in Scarthyla by a chromosome fusion event. The diploid number of X. truncata corroborates the character state of 2n = 30 as a synapomorphy of Dendropsophus. PMID:24107475

  2. Chromosome duplication in Lolium multiflorum Lam.

    Directory of Open Access Journals (Sweden)

    Roselaine Cristina Pereira

    2014-11-01

    Full Text Available Artificial chromosome duplication of diploid genotypes of Lolium multiflorum (2n=2x=14 is worthy to breeding, and aims to increase the expression of traits with agronomic interest. The purpose of this study was to obtain polyploid plants of L. multiflorum from local diploid populations in order to exploit adaptation and future verification of the effects of polyploidy in agronomic traits. Seedlings were immersed in different colchicine solutions for an exposure time of 3h and 24h. Ploidy determination was made by the DNA content and certified by chromosomes counts. The plants confirmed as tetraploids were placed in a greenhouse, and, at flowering, pollen viability was evaluated, and seeds were harvested to assess the stability of the progenies. The percentage of polyploids obtained was 20%. Pollen viability of the tetraploids generated ranged from 58% to 69%. The tetraploid plants obtained in the experiment generated 164 progenies, of which 109 presented DNA content compatible with the tetraploid level, showing stability of chromosome duplication in the filial generation.

  3. Sex determination by chromosome manipulation in fish

    International Nuclear Information System (INIS)

    Since it is impossible to artificially remove only sex chromosomes in sperm, gamma- or UV-irradiation has been used in destroying all chromosomes without loss of abilities of sperm movement and egg activation. It has been shown that a dose of gamma rays required for this purpose is 105 rad in any species of fish. For UV-irradiation, a 15 W lamp is used and irradiation for 60 to 120 seconds is required. With such an irradiation technique, gynogenetic haploid embryogenesis is induced. In developing normal diploid embryos of eggs inseminated with irradiated sperm (gynogenetic diploid embryogenesis with XX type), it is furthermore necessary to use physical procedures, such as low or high temperature and hydrostatic pressure. Irradiated sperm of different species of fish has also been used in inducing gynogenesis. As the most desirable technique, it is proposed to physiologically convert the sex of gynogenetic diploid embryos into males and to use sperm from those physiological males with XX chromosomes. Theoretical possibility of developing androgenetic haploid embryogenesis has been suggested. (Namekawa, K.)

  4. Evaluating the Relationship between Spermatogenic Silencing of the X Chromosome and Evolution of the Y Chromosome in Chimpanzee and Human

    Science.gov (United States)

    Mulugeta Achame, Eskeatnaf; Baarends, Willy M.; Gribnau, Joost; Grootegoed, J. Anton

    2010-01-01

    Chimpanzees and humans are genetically very similar, with the striking exception of their Y chromosomes, which have diverged tremendously. The male-specific region (MSY), representing the greater part of the Y chromosome, is inherited from father to son in a clonal fashion, with natural selection acting on the MSY as a unit. Positive selection might involve the performance of the MSY in spermatogenesis. Chimpanzees have a highly polygamous mating behavior, so that sperm competition is thought to provide a strong selective force acting on the Y chromosome in the chimpanzee lineage. In consequence of evolution of the heterologous sex chromosomes in mammals, meiotic sex chromosome inactivation (MSCI) results in a transcriptionally silenced XY body in male meiotic prophase, and subsequently also in postmeiotic repression of the sex chromosomes in haploid spermatids. This has evolved to a situation where MSCI has become a prerequisite for spermatogenesis. Here, by analysis of microarray testicular expression data representing a small number of male chimpanzees and men, we obtained information indicating that meiotic and postmeiotic X chromosome silencing might be more effective in chimpanzee than in human spermatogenesis. From this, we suggest that the remarkable reorganization of the chimpanzee Y chromosome, compared to the human Y chromosome, might have an impact on its meiotic interactions with the X chromosome and thereby on X chromosome silencing in spermatogenesis. Further studies will be required to address comparative functional aspects of MSCI in chimpanzee, human, and other placental mammals. PMID:21179482

  5. Estimating tempo and mode of Y chromosome turnover: explaining Y chromosome loss with the fragile Y hypothesis.

    Science.gov (United States)

    Blackmon, Heath; Demuth, Jeffery P

    2014-06-01

    Chromosomal sex determination is phylogenetically widespread, having arisen independently in many lineages. Decades of theoretical work provide predictions about sex chromosome differentiation that are well supported by observations in both XY and ZW systems. However, the phylogenetic scope of previous work gives us a limited understanding of the pace of sex chromosome gain and loss and why Y or W chromosomes are more often lost in some lineages than others, creating XO or ZO systems. To gain phylogenetic breadth we therefore assembled a database of 4724 beetle species' karyotypes and found substantial variation in sex chromosome systems. We used the data to estimate rates of Y chromosome gain and loss across a phylogeny of 1126 taxa estimated from seven genes. Contrary to our initial expectations, we find that highly degenerated Y chromosomes of many members of the suborder Polyphaga are rarely lost, and that cases of Y chromosome loss are strongly associated with chiasmatic segregation during male meiosis. We propose the "fragile Y" hypothesis, that recurrent selection to reduce recombination between the X and Y chromosome leads to the evolution of a small pseudoautosomal region (PAR), which, in taxa that require XY chiasmata for proper segregation during meiosis, increases the probability of aneuploid gamete production, with Y chromosome loss. This hypothesis predicts that taxa that evolve achiasmatic segregation during male meiosis will rarely lose the Y chromosome. We discuss data from mammals, which are consistent with our prediction. PMID:24939995

  6. Phosphatidylinositol-3-kinase-dependent phosphorylation of SLP-76 by the lymphoma-associated ITK-SYK fusion-protein

    International Nuclear Information System (INIS)

    Recurrent chromosomal translocations have long been implicated in various types of lymphomas and other malignancies. Novel recurrent t(5;9)(q33;q22) has been recently discovered in un-specified peripheral T-cell lymphoma. To elucidate the role of this translocation, the corresponding fusion construct encoding the N-terminal portion of the ITK kinase and the C-terminal catalytic region of the SYK kinase was generated. We herein show that the ITK-SYK fusion-protein is constitutively active. Moreover, we demonstrate that ITK-SYK is phosphorylated on key tyrosine residues and is capable of potently phosphorylating the related adapter proteins BLNK and SLP-76. In transiently transfected cells, SYK was phosphorylated at Y352 but not detectably at the activation-loop tyrosines Y525/Y526. In contrast, ITK-SYK was phosphorylated both at Y212 and the activation-loop tyrosines Y385/Y386, corresponding to Y352 and Y525/Y526 in SYK, respectively. In resting primary lymphocytes, ITK-SYK predominantly localizes to the cell surface. In addition, we demonstrate that following stimulation, the ITK-SYK fusion-protein in cell lines translocates to the cell membrane and, moreover, that this phenomenon as well as SLP-76 phosphorylation are blocked upon phosphatidylinositol-3-kinase (PI3-kinase) inhibition.

  7. Aurora kinases as druggable targets in pediatric leukemia: heterogeneity in target modulation activities and cytotoxicity by diverse novel therapeutic agents.

    Directory of Open Access Journals (Sweden)

    Aarthi Jayanthan

    Full Text Available Leukemia is the most common pediatric malignancy, constituting more than 30% of all childhood cancers. Although cure rates have improved greatly, approximately one in five children relapse and poor survival rates post relapse remain a challenge. Given this, more effective and innovative therapeutic strategies are needed in order to improve prognosis. Aurora kinases, a family of serine/threonine kinases essential for the regulation of several mitotic processes, have been identified as potential targets for cancer therapeutics. Elevated expression of Aurora kinases has been demonstrated in several malignancies and is associated with aberrant mitotic activity, aneuploidy and alterations in chromosomal structure and genome instability. Based on this rationale, a number of small molecule inhibitors have been formulated and advanced to human studies in the recent past. A comparative analysis of these agents in cytotoxicity and target modulation analyses against a panel of leukemia cells provides novel insights into the unique mechanisms and codependent activity pathways involved in targeting Aurora kinases, constituting a distinctive preclinical experimental framework to identify appropriate agents and combinations in future clinical studies.

  8. High Chromosome Number in hematological cancer cell lines is a Negative Predictor of Response to the inhibition of Aurora B and C by GSK1070916

    Directory of Open Access Journals (Sweden)

    Hardwicke Mary

    2011-07-01

    Full Text Available Abstract Background Aurora kinases play critical roles in mitosis and are being evaluated as therapeutic targets in cancer. GSK1070916 is a potent, selective, ATP competitive inhibitor of Aurora kinase B and C. Translation of predictive biomarkers to the clinic can benefit patients by identifying the tumors that are more likely to respond to therapies, especially novel inhibitors such as GSK1070916. Methods 59 Hematological cancer-derived cell lines were used as models for response where in vitro sensitivity to GSK1070916 was based on both time and degree of cell death. The response data was analyzed along with karyotype, transcriptomics and somatic mutation profiles to determine predictors of response. Results 20 cell lines were sensitive and 39 were resistant to treatment with GSK1070916. High chromosome number was more prevalent in resistant cell lines (p-value = 0.0098, Fisher Exact Test. Greater resistance was also found in cell lines harboring polyploid subpopulations (p-value = 0.00014, Unpaired t-test. A review of NOTCH1 mutations in T-ALL cell lines showed an association between NOTCH1 mutation status and chromosome number (p-value = 0.0066, Fisher Exact Test. Conclusions High chromosome number associated with resistance to the inhibition of Aurora B and C suggests cells with a mechanism to bypass the high ploidy checkpoint are resistant to GSK1070916. High chromosome number, a hallmark trait of many late stage hematological malignancies, varies in prevalence among hematological malignancy subtypes. The high frequency and relative ease of measurement make high chromosome number a viable negative predictive marker for GSK1070916.

  9. Using 3-color chromosome painting to decide between chromosome aberration models

    International Nuclear Information System (INIS)

    Ionizing radiation produces chromosome aberrations when DNA double strand breaks (DSB) interact pairwise. For more than 30 years there have been two main, competing theories of such binary DSB interactions. The classical theory asserts that an unrepaired DSB makes two ends which separate, with each end subsequently able to join any similar (non-telomeric) end. The exchange theory asserts that the two DSB ends remain associated until repair or a reciprocal chromosome exchange involving a second DSB occurs. The authors conducted an experiment to test these models, using 3-color chromosome painting. After in vitro irradiation of resting human lymphocytes, they observed cells with three-color triplets at first metaphase: three derivative chromosomes having permuted colors, as if three broken chromosomes had played musical chairs. On the exchange model in its standard form such 3-color triplets cannot occur. On the classical model the expected frequency can be calculated. They report data and computer calculations which exclude the exchange model and favor the classical model

  10. Dynamic changes in paternal X-chromosome activity during imprinted X-chromosome inactivation in mice.

    Science.gov (United States)

    Patrat, Catherine; Okamoto, Ikuhiro; Diabangouaya, Patricia; Vialon, Vivian; Le Baccon, Patricia; Chow, Jennifer; Heard, Edith

    2009-03-31

    In mammals, X-chromosome dosage compensation is achieved by inactivating one of the two X chromosomes in females. In mice, X inactivation is initially imprinted, with inactivation of the paternal X (Xp) chromosome occurring during preimplantation development. One theory is that the Xp is preinactivated in female embryos, because of its previous silence during meiosis in the male germ line. The extent to which the Xp is active after fertilization and the exact time of onset of X-linked gene silencing have been the subject of debate. We performed a systematic, single-cell transcriptional analysis to examine the activity of the Xp chromosome for a panel of X-linked genes throughout early preimplantation development in the mouse. Rather than being preinactivated, we found the Xp to be fully active at the time of zygotic gene activation, with silencing beginning from the 4-cell stage onward. X-inactivation patterns were, however, surprisingly diverse between genes. Some loci showed early onset (4-8-cell stage) of X inactivation, and some showed extremely late onset (postblastocyst stage), whereas others were never fully inactivated. Thus, we show that silencing of some X-chromosomal regions occurs outside of the usual time window and that escape from X inactivation can be highly lineage specific. These results reveal that imprinted X inactivation in mice is far less concerted than previously thought and highlight the epigenetic diversity underlying the dosage compensation process during early mammalian development. PMID:19273861

  11. Chromosomal rearrangements and karyotype evolution in carnivores revealed by chromosome painting.

    Science.gov (United States)

    Nie, W; Wang, J; Su, W; Wang, D; Tanomtong, A; Perelman, P L; Graphodatsky, A S; Yang, F

    2012-01-01

    Chromosomal evolution in carnivores has been revisited extensively using cross-species chromosome painting. Painting probes derived from flow-sorted chromosomes of the domestic dog, which has one of the most rearranged karyotypes in mammals and the highest dipoid number (2n=78) in carnivores, are a powerful tool in detecting both evolutionary intra- and inter-chromosomal rearrangements. However, only a few comparative maps have been established between dog and other non-Canidae species. Here, we extended cross-species painting with dog probes to seven more species representing six carnivore families: Eurasian lynx (Lynx lynx), the stone marten (Martes foina), the small Indian civet (Viverricula indica), the Asian palm civet (Paradoxurus hermaphrodites), Javan mongoose (Hepestes javanicas), the raccoon (Procyon lotor) and the giant panda (Ailuropoda melanoleuca). The numbers and positions of intra-chromosomal rearrangements were found to differ among these carnivore species. A comparative map between human and stone marten, and a map among the Yangtze finless porpoise (Neophocaena phocaenoides asiaeorientalis), stone marten and human were also established to facilitate outgroup comparison and to integrate comparative maps between stone marten and other carnivores with such maps between human and other species. These comparative maps give further insight into genome evolution and karyotype phylogenetic relationships among carnivores, and will facilitate the transfer of gene mapping data from human, domestic dog and cat to other species. PMID:22086079

  12. The relationship between induced chromosome aberrations and chromosome abnormality in tumour cells

    International Nuclear Information System (INIS)

    The occurrence of chromosome abnormalities in cancer cells and the induction of chromosome aberrations by many different carcinogenic agents are now well established facts and there are many detailed studies in both areas. It is known, however, whether or not there is any relationship between the induced aberrations and those seen in tumours. The purpose of this paper is to consider any evidence which might suggest that such a relationship does exist and the significance that this would have in the genesis of neoplasia. There are at least four chromosomal situations in human tumours: (a) cytogenetically normal, (b) clonal but unique, (c) clonal and specific for a particular neoplasm, (d) clonal and common to some tumours of different types. Any theory that we develop must take account of all four situations. A number of different suggestions have been made to try to explain the observation of chromosome abnormalities in human tumours. The one feature that does seem common to all situations is clonal evolution. A modified somatic mutation hypothesis to account for the chromosome changes occurring before and after malignant transformation is suggested

  13. Chromosomal rearrangements and karyotype evolution in carnivores revealed by chromosome painting

    Science.gov (United States)

    Nie, W; Wang, J; Su, W; Wang, D; Tanomtong, A; Perelman, P L; Graphodatsky, A S; Yang, F

    2012-01-01

    Chromosomal evolution in carnivores has been revisited extensively using cross-species chromosome painting. Painting probes derived from flow-sorted chromosomes of the domestic dog, which has one of the most rearranged karyotypes in mammals and the highest dipoid number (2n=78) in carnivores, are a powerful tool in detecting both evolutionary intra- and inter-chromosomal rearrangements. However, only a few comparative maps have been established between dog and other non-Canidae species. Here, we extended cross-species painting with dog probes to seven more species representing six carnivore families: Eurasian lynx (Lynx lynx), the stone marten (Martes foina), the small Indian civet (Viverricula indica), the Asian palm civet (Paradoxurus hermaphrodites), Javan mongoose (Hepestes javanicas), the raccoon (Procyon lotor) and the giant panda (Ailuropoda melanoleuca). The numbers and positions of intra-chromosomal rearrangements were found to differ among these carnivore species. A comparative map between human and stone marten, and a map among the Yangtze finless porpoise (Neophocaena phocaenoides asiaeorientalis), stone marten and human were also established to facilitate outgroup comparison and to integrate comparative maps between stone marten and other carnivores with such maps between human and other species. These comparative maps give further insight into genome evolution and karyotype phylogenetic relationships among carnivores, and will facilitate the transfer of gene mapping data from human, domestic dog and cat to other species. PMID:22086079

  14. 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

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

    Institute of Scientific and Technical Information of China (English)

    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.

  16. Non-degradative Ubiquitination of Protein Kinases.

    Directory of Open Access Journals (Sweden)

    K Aurelia Ball

    2016-06-01

    Full Text Available Growing evidence supports other regulatory roles for protein ubiquitination in addition to serving as a tag for proteasomal degradation. In contrast to other common post-translational modifications, such as phosphorylation, little is known about how non-degradative ubiquitination modulates protein structure, dynamics, and function. Due to the wealth of knowledge concerning protein kinase structure and regulation, we examined kinase ubiquitination using ubiquitin remnant immunoaffinity enrichment and quantitative mass spectrometry to identify ubiquitinated kinases and the sites of ubiquitination in Jurkat and HEK293 cells. We find that, unlike phosphorylation, ubiquitination most commonly occurs in structured domains, and on the kinase domain, ubiquitination is concentrated in regions known to be important for regulating activity. We hypothesized that ubiquitination, like other post-translational modifications, may alter the conformational equilibrium of the modified protein. We chose one human kinase, ZAP-70, to simulate using molecular dynamics with and without a monoubiquitin modification. In Jurkat cells, ZAP-70 is ubiquitinated at several sites that are not sensitive to proteasome inhibition and thus may have other regulatory roles. Our simulations show that ubiquitination influences the conformational ensemble of ZAP-70 in a site-dependent manner. When monoubiquitinated at K377, near the C-helix, the active conformation of the ZAP-70 C-helix is disrupted. In contrast, when monoubiquitinated at K476, near the kinase hinge region, an active-like ZAP-70 C-helix conformation is stabilized. These results lead to testable hypotheses that ubiquitination directly modulates kinase activity, and that ubiquitination is likely to alter structure, dynamics, and function in other protein classes as well.

  17. Chromosome Synapsis Alleviates Mek1-Dependent Suppression of Meiotic DNA Repair.

    Directory of Open Access Journals (Sweden)

    Vijayalakshmi V Subramanian

    2016-02-01

    Full Text Available Faithful meiotic chromosome segregation and fertility require meiotic recombination between homologous chromosomes rather than the equally available sister chromatid, a bias that in Saccharomyces cerevisiae depends on the meiotic kinase, Mek1. Mek1 is thought to mediate repair template bias by specifically suppressing sister-directed repair. Instead, we found that when Mek1 persists on closely paired (synapsed homologues, DNA repair is severely delayed, suggesting that Mek1 suppresses any proximal repair template. Accordingly, Mek1 is excluded from synapsed homologues in wild-type cells. Exclusion requires the AAA+-ATPase Pch2 and is directly coupled to synaptonemal complex assembly. Stage-specific depletion experiments further demonstrate that DNA repair in the context of synapsed homologues requires Rad54, a repair factor inhibited by Mek1. These data indicate that the sister template is distinguished from the homologue primarily by its closer proximity to inhibitory Mek1 activity. We propose that once pairing or synapsis juxtaposes homologues, exclusion of Mek1 is necessary to avoid suppression of all templates and accelerate repair progression.

  18. New auroras on the roles of the Chromosomal Passenger Complex in cytokinesis: implications for cancer therapies

    Directory of Open Access Journals (Sweden)

    Pier Paolo eD'Avino

    2015-10-01

    Full Text Available The Chromosomal Passenger Complex (CPC, composed of a kinase component, Aurora B, the scaffolding subunit Inner Centromeric Protein (INCENP, Borealin, and Survivin, is a key regulator of cell division. It controls multiple events, from chromosome condensation in prophase to the final separation or abscission of the two daughter cells. The essential functions of the CPC during metaphase, however, have always hindered an accurate study of its role during cytokinesis. The recent development of small molecule inhibitors against Aurora B and the use of elegant technologies such as chemical genetics have offered new approaches to study the functions of the CPC at the end of cell division. Here we review the recent findings about the roles of the CPC in controlling the assembly of the cleavage furrow, central spindle and midbody. We will also discuss the crucial function of this complex in controlling abscission timing in order to prevent abscission when lagging chromatin is present at the cleavage site, thereby avoiding the formation of genetically abnormal daughter cells. Finally, we offer our perspective on how to exploit the potential therapeutic applications of inhibiting CPC activity during cytokinesis in cancer cells.

  19. Phospho-kinase profile of colorectal tumors guides in the selection of multi-kinase inhibitors.

    Science.gov (United States)

    Serrano-Heras, Gemma; Cuenca-López, María Dolores; Montero, Juan Carlos; Corrales-Sanchez, Verónica; Morales, Jorge Carlos; Núñez, Luz-Elena; Morís, Francisco; Pandiella, Atanasio; Ocaña, Alberto

    2015-10-13

    Protein kinases play a central role in the oncogenesis of colorectal tumors and are attractive druggable targets. Detection of activated kinases within a tumor could open avenues for drug selection and optimization of new kinase inhibitors. By using a phosphokinase arrays with human colorectal tumors we identified activated kinases, including the Epidermal Growth Factor Receptor (EGFR), components of the PI3K/mTOR pathway (AKT and S6), and STAT, among others. A pharmacological screening with kinase inhibitors against these proteins helped us to identify a new kinase inhibitor, termed EC-70124 that showed the highest anti-proliferative activity in cell lines. EC-70124 also inhibited cell migration and biochemical experiments demonstrated its effect targeting the PI3K/mTOR pathway. This drug also arrested cells at G2/M and induced apoptosis. Experiments in combination with standard chemotherapy used in the clinical setting indicated a synergistic effect. EC-70124 also reduced tumor growth in vivo and inhibited pS6 in the implanted tumors. In conclusion, by studying the kinase profile of colorectal tumors, we identified relevant activated pathways, and a new multi-kinase compound with significant antitumor properties. PMID:26418718

  20. CDPKs are dual-specificity protein kinases and tyrosine autophosphorylation attenuates kinase activity

    Science.gov (United States)

    Calcium-dependent protein kinases (CDPKs or CPKs) are classified as serine/threonine protein kinases but we made the surprising observation that soybean CDPK' and several Arabidopsis isoforms (AtCPK4 and AtCPK34) could also autophosphorylate on tyrosine residues. In studies with His6-GmCDPK', we ide...