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Sample records for bcl-1 gene rearrangement

  1. Diagnosis of mantle cell lymphoma and detection of bcl-1 gene rearrangement

    International Nuclear Information System (INIS)

    We reclassified a large series of non-Hogkin's lymphoma diagnosed at Korea Cancer Center Hospital from 1991 to 1995, according to REAL classification, and compared the efficacy of immunohistochemical study for cyclin D1 protein and PCR for bcl-1 gene rearrangement to diagnose mantle cell lymphoma (MCL). By REAL classification, 7 %, diffuse large B-cell lymphoma was the most common type (51.8%) and was followed by peripheral T-cell lymphoma-unspecified (10%) and angiocentric lymphoma (7.5%). The most reliable histologic finding was mitosis to make a differential diagnosis. Mitoses of MCL were 17/10 HPF in average and all the cases showed more than 10/10 HPF. Immunophenotypic study alone cannot lead to a differential diagnosis between MCL and SLL, and the overexpression of cyclin D1 was the most important for diagnosis of MCL . Both immunohistochemistry for cyclin D1 and PCR for bcl-1 were specific for MCL and immunohistochemistry was more sensitive than PCR. Statistical analysis showed a different survival rate between MCL and the other low-grade B-cell lymphomas (SLL + MALT + LPL) and a difference between MCL and SLL. Immunohistochemical detection of cyclin D1 has a practical usefulness in making routine diagnosis of MCL. The initial accurate diagnosis of MCL will help clinicians make a proper management. (author). 27 refs., 6 tabs., 4 figs

  2. Diagnosis of mantle cell lymphoma and detection of bcl-1 gene rearrangement

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    Lee, Seung Sook; Cho, Kyung Ja; Lee, Sun Joo [Korea Cancer Center Hospital, Seoul (Korea, Republic of)

    1996-12-01

    We reclassified a large series of non-Hogkin`s lymphoma diagnosed at Korea Cancer Center Hospital from 1991 to 1995, according to REAL classification, and compared the efficacy of immunohistochemical study for cyclin D1 protein and PCR for bcl-1 gene rearrangement to diagnose mantle cell lymphoma (MCL). By REAL classification, 7 %, diffuse large B-cell lymphoma was the most common type (51.8%) and was followed by peripheral T-cell lymphoma-unspecified (10%) and angiocentric lymphoma (7.5%). The most reliable histologic finding was mitosis to make a differential diagnosis. Mitoses of MCL were 17/10 HPF in average and all the cases showed more than 10/10 HPF. Immunophenotypic study alone cannot lead to a differential diagnosis between MCL and SLL, and the overexpression of cyclin D1 was the most important for diagnosis of MCL . Both immunohistochemistry for cyclin D1 and PCR for bcl-1 were specific for MCL and immunohistochemistry was more sensitive than PCR. Statistical analysis showed a different survival rate between MCL and the other low-grade B-cell lymphomas (SLL + MALT + LPL) and a difference between MCL and SLL. Immunohistochemical detection of cyclin D1 has a practical usefulness in making routine diagnosis of MCL. The initial accurate diagnosis of MCL will help clinicians make a proper management. (author). 27 refs., 6 tabs., 4 figs.

  3. Multiplex PCR for the detection of BCL-1/IGH and BCL-2/IGH gene rearrangements--clinical validation in a prospective study of blood and bone marrow in 258 patients with or suspected of non-Hodgkin's lymphoma

    DEFF Research Database (Denmark)

    Nyvold, Charlotte G; Bendix, Knud; Brandsborg, Margrethe;

    2007-01-01

    We have designed a multiplex PCR, which allows for fast and high throughput demonstration of the BCL-1/IGH and BCL-2/IGH fusion DNA observed primarily in mantle cell- and follicular non-Hodgkin's lymphoma (NHL). Blood (PB) and/or bone marrow (BM) from 258 patients suspected of NHL have...

  4. Gene conversion in human rearranged immunoglobulin genes.

    Science.gov (United States)

    Darlow, John M; Stott, David I

    2006-07-01

    Over the past 20 years, many DNA sequences have been published suggesting that all or part of the V(H) segment of a rearranged immunoglobulin gene may be replaced in vivo. Two different mechanisms appear to be operating. One of these is very similar to primary V(D)J recombination, involving the RAG proteins acting upon recombination signal sequences, and this has recently been proven to occur. Other sequences, many of which show partial V(H) replacements with no addition of untemplated nucleotides at the V(H)-V(H) joint, have been proposed to occur by an unusual RAG-mediated recombination with the formation of hybrid (coding-to-signal) joints. These appear to occur in cells already undergoing somatic hypermutation in which, some authors are convinced, RAG genes are silenced. We recently proposed that the latter type of V(H) replacement might occur by homologous recombination initiated by the activity of AID (activation-induced cytidine deaminase), which is essential for somatic hypermutation and gene conversion. The latter has been observed in other species, but not in human Ig genes, so far. In this paper, we present a new analysis of sequences published as examples of the second type of rearrangement. This not only shows that AID recognition motifs occur in recombination regions but also that some sequences show replacement of central sections by a sequence from another gene, similar to gene conversion in the immunoglobulin genes of other species. These observations support the proposal that this type of rearrangement is likely to be AID-mediated rather than RAG-mediated and is consistent with gene conversion.

  5. Divergence of gene regulation through chromosomal rearrangements

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    Messing Joachim

    2010-11-01

    Full Text Available Abstract Background The molecular mechanisms that modify genome structures to give birth and death to alleles are still not well understood. To investigate the causative chromosomal rearrangements, we took advantage of the allelic diversity of the duplicated p1 and p2 genes in maize. Both genes encode a transcription factor involved in maysin synthesis, which confers resistance to corn earworm. However, p1 also controls accumulation of reddish pigments in floral tissues and has therefore acquired a new function after gene duplication. p1 alleles vary in their tissue-specific expression, which is indicated in their allele designation: the first suffix refers to red or white pericarp pigmentation and the second to red or white glume pigmentation. Results Comparing chromosomal regions comprising p1-ww[4Co63], P1-rw1077 and P1-rr4B2 alleles with that of the reference genome, P1-wr[B73], enabled us to reconstruct additive events of transposition, chromosome breaks and repairs, and recombination that resulted in phenotypic variation and chimeric regulatory signals. The p1-ww[4Co63] null allele is probably derived from P1-wr[B73] by unequal crossover between large flanking sequences. A transposon insertion in a P1-wr-like allele and NHEJ (non-homologous end-joining could have resulted in the formation of the P1-rw1077 allele. A second NHEJ event, followed by unequal crossover, probably led to the duplication of an enhancer region, creating the P1-rr4B2 allele. Moreover, a rather dynamic picture emerged in the use of polyadenylation signals by different p1 alleles. Interestingly, p1 alleles can be placed on both sides of a large retrotransposon cluster through recombination, while functional p2 alleles have only been found proximal to the cluster. Conclusions Allelic diversity of the p locus exemplifies how gene duplications promote phenotypic variability through composite regulatory signals. Transposition events increase the level of genomic complexity

  6. Sterile DJH rearrangements reveal that distance between gene segments on the human Ig H chain locus influences their ability to rearrange

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    Hansen, Tina Østergaard; Lange, Anders Blaabjerg; Barington, Torben

    2015-01-01

    Rearrangement of the Ig locus occurs in two steps. First, a JH gene is rearranged to a D gene followed by a VH gene rearranging to the DJH rearrangement. By next generation sequencing, we analyzed 9969 unique DJH rearrangements and 5919 unique VHDJH rearrangements obtained from peripheral blood B...... frequently than JH locus distal D genes, whereas VH locus proximal D genes were observed more frequently in nonproductive VHDJH rearrangements. We further demonstrate that the distance between VH, D, and JH gene segments influence their ability to rearrange within the human Ig locus....

  7. Androgen receptor gene mutation, rearrangement, polymorphism.

    Science.gov (United States)

    Eisermann, Kurtis; Wang, Dan; Jing, Yifeng; Pascal, Laura E; Wang, Zhou

    2013-09-01

    Genetic aberrations of the androgen receptor (AR) caused by mutations, rearrangements, and polymorphisms result in a mutant receptor that has varied functions compared to wild type AR. To date, over 1,000 mutations have been reported in the AR with most of these being associated with androgen insensitivity syndrome (AIS). While mutations of AR associated with prostate cancer occur less often in early stage localized disease, mutations in castration-resistant prostate cancer (CRPC) patients treated with anti-androgens occur more frequently with 10-30% of these patients having some form of mutation in the AR. Resistance to anti-androgen therapy usually results from gain-of-function mutations in the LBD such as is seen with bicalutamide and more recently with enzalutamide (MDV3100). Thus, it is crucial to investigate these new AR mutations arising from drug resistance to anti-androgens and other small molecule pharmacological agents.

  8. Gene Rearrangement Analysis of Orbital Lymphoid Infilktrating Disorders

    Institute of Scientific and Technical Information of China (English)

    JianghuaYan; ZhongyaoWu; 等

    2002-01-01

    Purpose:To determine whether the use of polymerae chain reaction for B-cell gene rearrangement in patients with orbital lymphoid infiltrate disorders could be useful in the diagnosis of lymphoma,especially,in differentiating benign lesion from malignant one.Methoids:In addition to clinical,pathological,and immunohistochemical evaluatons,48 cases of orbital lymphoid infiltrate disorders were examined for immunoglobulin heavy (IgH) gene rearrangement by means of PCR to amplify the FR3 region with formalin-fixed and paraffin-embedded tissues.Results:Gene rearrangement in the third frame-work of the IgH region was detected in specimens obtained from 15 cases of malignant lymphoma,4 of reactive lymphoid hyperplasia and 3 of orbital pseudotumor.All of these patients showed a discrete band (100bp) which reflected monoclonal proliferation of B lymphocytes.5 cases of malignant lymphoma,6 of reactive lymphoid hyperplasia and 15 of orbital pseudotumor did not show a discrete band on PCR.Conclusions:The FR3 region gene rearrangement of Ig heavy in patients with orbital lymphoid infilktrate disorders may be an additional diagnostic tool in differentiating benign from malignant lymphoid diseases and in offering a useful adjunct for diagnosis in difficult or unclear case.It is a reliable and practical method of gene diagnosis in orbital lymphoid infiltrate disorders and helps to identife the molecular mechanism of malignant lymphoma.Eye Science 2000;16:15-21.

  9. Gene Rearrangement Analysis of Orbital Lymphoid Infiltrating Disorders

    Institute of Scientific and Technical Information of China (English)

    Jianhua Yan; Zhongyao Wu; Shuqi Huang; Yongping Li

    2000-01-01

    Purpose: To determine whether the use of polymerase chain reaction for B-cell gene rearrangement in patients with orbital lymphoid infiltrate disorders could be useful in the diagnosis of lymphoma, especially, in differentiating benign lesion from malignant one. Methods: In addition to clinical, pathological, and immunohistochemical evaluations,48 cases of orbital lymphoid infiltrate disorders were examined for immunoglobulin heavy (IgH) gene rearrangement by means of PCR to amplify the FR3 region with formalin-fixed and paraffin-embedded tissues. Results: Gene rearrangement in the third frame-work of the IgH region was detected in specimens obtained from 15 cases of malignant lymphoma, 4 of reactive lymphoid hyperplasia and 3 of orbital pseudotumor. All of these patients showed a discrete band (100bp) which reflected monoclonal proliferation of B lymphocytes. 5 cases of malignant lymphoma, 6 of reactive lymphoid hyperplasia and 15 of orbital pseudotumor did not show a discrete band on PCR. Conclusions: The FR3 region gene rearrangement of Ig heavy in patients with orbital lymphoid infiltrate disorders may be an additional diagnostic tool in differentiating benign from malignant lymphoid diseases and in offering a useful adjunct for diagnosis in difficult or unclear cases. It is a reliable and practical method of gene diagnosis in orbital lymphoid infiltrate disorders and helps to identify the molecular mechanism of malignant lymphoma. Eye Science 2000; 16:15 ~ 21.

  10. Rearrangements of immunoglobulin genes during differentiation and evolution.

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    Honjo, T; Nakai, S; Nishida, Y; Kataoka, T; Yamawaki-Kataoka, Y; Takahashi, N; Obata, M; Shimizu, A; Yaoita, Y; Nikaido, T; Ishida, N

    1981-01-01

    Immunoglobulin genes are shown to undergo dynamic rearrangements during differentiation as well as evolution. We have demonstrated that a complete immunoglobulin heavy chain gene is formed by at least two types of DNA rearrangement during B cell differentiation. The first type of rearrangement is V-D-J recombination to complete a variable region sequence and the second type is S-S recombination to switch a constant region sequence. Both types of recombination are accompanied by deletion of the intervening DNA segment. Structure and organization of CH genes are elucidated by molecular cloning and nucleotide sequence determination. Organization of H chain genes is summarized as VH-(unknown distance)-JH-(6.5 kb)-C mu-(4.5 kb)-C delta-(unknown distance)-C gamma 3-(34 kb)-C gamma 1-(21 kb)-C gamma 2b-(15 kb)-C gamma 2a-(14.5 kb)-C epsilon-(12.5 kb)-C alpha. The S-S recombination takes place at the S region which is located at the 5' side of each CH gene. Nucleotide sequence of the S region comprises tandem repetition of closely related sequences. The S-S recombination seems to be mediated by short common sequences shared among S regions. A sister chromatid exchange model was proposed as a mechanism for S-S recombination. Comparison of nucleotide sequences of CH genes indicates that immunoglobulin genes have scrambled by intervening sequence-mediated domain transfer during their evolution.

  11. THE RELATIONSHIP BETWEEN NON-HODGKIN'S LYMPHOMA AND THE GENE REARRANGEMENT

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    Guo Sutang; Liu Yongchang; Sun Junning

    1998-01-01

    Objective:To investigate the pattern of clonal rearrangement of immunoglobulin heavy chain gene (IGH) and T-cell receptor γ gene (TCRγ) of NonHodgkin's lymphoma (NHL). Methods: Bone marrow smears of 211 patients of NHL were detected by PCR, the rearranged IGH and TCRγ gene was amplified using oligonucleotide primers. Results: The clonal rearrangement of IGH gene was detectable in 51.2%(108/211); the clonal rearrangement of TCRγ gene was detectable in 21.3% (45/211); both IGH and TCRγwas detectable in 5.7% (12/211);no clonal rearrangement in 21.8% (46/211). And compared clonal gene rearrangement with pathological type and primary site of tumor. Ten patients of NHL were investigated serially. 5/10 patients still had clonal gene rearrangement at clinical complete remission. Conclusion: It demonstrated that this assay may be useful in monitoring the minimal residual disease (MRD) and in evaluating effectiveness of therapy.

  12. Bcl-1 gene rearrangements in mantle cell lymphoma : A comprehensive analysis of 118 cases, including B-5-fixed tissue, by polymerase chain reaction and southern transfer analysis

    NARCIS (Netherlands)

    Chibbar, R; Leung, K; McCormick, S; Ritzkalla, K; Strickler, J; Staggs, R; Poppema, S; Brunning, RD; McGlennen, RC

    1998-01-01

    We evaluated 118 cases of mantle cell lymphoma by polymerase chain reaction (PCR) for the major translocation cluster (MIG) region and another breakpoint corresponding to probe p94(PS), located 24 kb telomeric to the MTC locus on chromosome 11. The specimens included 64 frozen, 19 formalin-fixed, an

  13. Diagnostic significance of TCR gene clonal rearrangement analysis in early mycosis fungoides

    Institute of Scientific and Technical Information of China (English)

    Chen Xu; Chuan Wan; Lin Wang; Han-Jun Yang; Yuan Tang; Wei-Ping Liu

    2011-01-01

    Mycosis fungoides (MF), the most common type of cutaneous T-cell lymphoma, has various unspecific clinical and histological characteristics. Its eariy diagnosis is challenging. The application of T-cell receptor (TCR) gene clonal rearrangement to the diagnosis of MF has been widely studied. In this study, we used polymerase chain reaction (PCR) to investigate the diagnostic significance of detecting TCR-γ and -β gene clonal rearrangement in the eady diagnosis of mycosis fungoides. PCR for TCR-γ and TCR-β gene rearrangement was performed on 19 patients with suspected early MF, 6 with typical MF, and 6 with chronic dermatitis. Of the 19 patients with suspected eady MF, 13 had TCR-~ gene clonal rearrangement, whereas none had TCR-β gene clonal rearrangement. All patients with typical MF had TCR gene clonal rearrangement, in which 4 showed TCR-γ clonal rearrangement, 1 showed TCR-β gene clonal rearrangements, and 1 showed both. No patients with chronic dermatitis had TCR gene clonal rearrangement. These results indicate that TCR gene clonal rearrangement analysis is a useful tool in diagnosing early MF. TCR-γ gene is recommended to the routine analysis, whereas TCR-β gene has potential in combination toward intractable cases.

  14. Molecular screening of pituitary adenomas for gene mutations and rearrangements

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    Herman, V.; Drazin, N.Z.; Gonskey, R.; Melmed, S. (Cedars-Sinai Medical Center, Los Angeles, CA (United States))

    1993-07-01

    Although pituitary tumors arise as benign monoclonal neoplasms, genetic alterations have not readily been identified in these adenomas. The authors studied restriction fragment abnormalities involving the GH gene locus, and mutations in the p53 and H-, K-, and N-ras genes in 22 human GH cell adenomas. Twenty two nonsecretory adenomas were also examined for p53 and ras gene mutations. Seven prolactinoma DNA samples were tested for deletions in the multiple endocrine neoplasia-1 (MEN-1) locus, as well as for rearrangements in the hst gene, a member of the fibroblast growth factor family. In DNA from GH-cell adenomas, identical GH restriction patterns were detected in both pituitary and lymphocyte DNA in all patients and in one patient with a mixed GH-TSH cell adenoma. Using polymerase chain reaction (PCR)-single stranded conformation polymorphism analysis, no mutations were detected in exons 5, 6, 7 and 8 of the p53 gene in GH cell adenomas nor in 22 nonsecretory adenomas. Codons 12/13 and 61 of H-ras, K-ras, and N-ras genes were also intact on GH cell adenomas and in nonsecretory adenomas. Site-specific probes for chromosome 11q13 including, PYGM, D11S146, and INT2 were used in 7 sporadic PRL-secreting adenomas to detect deletions of the MEN-1 locus on chromosome 11. One patient was identified with a loss of 11p, and the remaining 6 patients did not demonstrate loss of heterozygosity in the pituitary 11q13 locus, compared to lymphocyte DNA. None of these patients demonstrated hst gene rearrangements which also maps to this locus. These results show that p53 and ras gene mutations are not common events in the pathogenesis of acromegaly and nonsecretory tumors. Although hst gene rearrangements and deletions of 11q13 are not associated with sporadic PRl-cell adenoma formation, a single patient was detected with a partial loss of chromosome 11, including the putative MEN-1 site. 31 refs., 5 figs., 2 tabs.

  15. The Control Level of Bronchial Asthma in Dependence of Genotype by BCL1 Polymorphism of Glucocorticoids Receptor Gene and Body Mass Index

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    Vladyslava V. Kmyta

    2014-09-01

    Full Text Available The frequency of allelic genotypes by BclI polymorphism glucocorticoids receptor gene (GR had been studied in dependence of the control level of bronchial asthma (BA and body mass index (BMI, and also- connection between those indicators. 188 patient with BA and 95 almost healthy humans were investigated. Determination of single nucleotide BclI polymorphism GR gene performed by the method of polymerase chain reaction with following analyze of the length of restriction fragments. Our studies demonstrated connection between BA control, BclI polymorphism GR gene and BMI. Proved, that distribution C/C, C/G and G/G genotypes by BclI polymorphism in patients with BA showed reliable difference between patients with different BMI and connection G/G genotype with obesity. The reliable difference in distributing of genotype in dependence of BA control level has been proved: with controlled BA reliably often met C/C genotype, without control – G/G genotype. Therefore, proved, that frequency G/G genotype by BclI polymorphism GR gene in patients with BA with obesity and absence of control for the flowing of disease is reliably higher, that confirmed the role of this genotype, likewise, in obesity occurrence, so in absence of the control of disease.

  16. Prevalence of chromosomal rearrangements involving non-ETS genes in prostate cancer.

    Science.gov (United States)

    Kluth, Martina; Galal, Rami; Krohn, Antje; Weischenfeldt, Joachim; Tsourlakis, Christina; Paustian, Lisa; Ahrary, Ramin; Ahmed, Malik; Scherzai, Sekander; Meyer, Anne; Sirma, Hüseyin; Korbel, Jan; Sauter, Guido; Schlomm, Thorsten; Simon, Ronald; Minner, Sarah

    2015-04-01

    Prostate cancer is characterized by structural rearrangements, most frequently including translocations between androgen-dependent genes and members of the ETS family of transcription factor like TMPRSS2:ERG. In a recent whole genome sequencing study we identified 140 gene fusions that were unrelated to ETS genes in 11 prostate cancers. The aim of the present study was to estimate the prevalence of non-ETS gene fusions. We randomly selected 27 of these rearrangements and analyzed them by fluorescence in situ hybridization (FISH) in a tissue microarray format containing 500 prostate cancers. Using break-apart FISH probes for one fusion partner each, we found rearrangements of 13 (48%) of the 27 analyzed genes in 300-400 analyzable cancers per gene. Recurrent breakage, often accompanied by partial deletion of the genes, was found for NCKAP5, SH3BGR and TTC3 in 3 (0.8%) tumors each, as well as for ARNTL2 and ENOX1 in 2 (0.5%) cancers each. One rearranged tumor sample was observed for each of VCL, ZNF578, IMMP2L, SLC16A12, PANK1, GPHN, LRP1 and ZHX2. Balanced rearrangements, indicating possible gene fusion, were found for ZNF578, SH3BGR, LPR12 and ZHX2 in individual cancers only. The results of the present study confirm that rearrangements involving non-ETS genes occur in prostate cancer, but demonstrate that they are highly individual and typically non-recurrent.

  17. Genomic characterization of large rearrangements of the LDLR gene in Czech patients with familial hypercholesterolemia

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    Fajkus Jiří

    2010-07-01

    Full Text Available Abstract Background Mutations in the LDLR gene are the most frequent cause of Familial hypercholesterolemia, an autosomal dominant disease characterised by elevated concentrations of LDL in blood plasma. In many populations, large genomic rearrangements account for approximately 10% of mutations in the LDLR gene. Methods DNA diagnostics of large genomic rearrangements was based on Multiple Ligation dependent Probe Amplification (MLPA. Subsequent analyses of deletion and duplication breakpoints were performed using long-range PCR, PCR, and DNA sequencing. Results In set of 1441 unrelated FH patients, large genomic rearrangements were found in 37 probands. Eight different types of rearrangements were detected, from them 6 types were novel, not described so far. In all rearrangements, we characterized their exact extent and breakpoint sequences. Conclusions Sequence analysis of deletion and duplication breakpoints indicates that intrachromatid non-allelic homologous recombination (NAHR between Alu elements is involved in 6 events, while a non-homologous end joining (NHEJ is implicated in 2 rearrangements. Our study thus describes for the first time NHEJ as a mechanism involved in genomic rearrangements in the LDLR gene.

  18. Immunoglobulin gene rearrangements and the pathogenesis of multiple myeloma

    NARCIS (Netherlands)

    Gonzalez, David; van der Burg, Mirjam; Garcia-Sanz, Ramon; Fenton, James A.; Langerak, Anton W.; Gonzalez, Marcos; van Dongen, Jacques J. M.; Miguel, Jesus F. San; Morgan, Gareth J.

    2007-01-01

    The ability to rearrange the germ-line DNA to generate antibody diversity is an essential prerequisite for the production of a functional repertoire. While this is essential to prevent infections, it also represents the "Achilles heal" of the B-cell lineage, occasionally leading to malignant transfo

  19. Marfan syndrome with a complex chromosomal rearrangement including deletion of the FBN1 gene

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    Colovati Mileny ES

    2012-01-01

    Full Text Available Abstract Background The majority of Marfan syndrome (MFS cases is caused by mutations in the fibrillin-1 gene (FBN1, mapped to chromosome 15q21.1. Only few reports on deletions including the whole FBN1 gene, detected by molecular cytogenetic techniques, were found in literature. Results We report here on a female patient with clinical symptoms of the MFS spectrum plus craniostenosis, hypothyroidism and intellectual deficiency who presents a 1.9 Mb deletion, including the FBN1 gene and a complex rearrangement with eight breakpoints involving chromosomes 6, 12 and 15. Discussion This is the first report of MFS with a complex chromosome rearrangement involving a deletion of FBN1 and contiguous genes. In addition to the typical clinical findings of the Marfan syndrome due to FBN1 gene haploinsufficiency, the patient presents features which may be due to the other gene deletions and possibly to the complex chromosome rearrangement.

  20. Family expansion and gene rearrangements contributed to the functional specialization of PRDM genes in vertebrates

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    Alcalay Myriam

    2007-10-01

    Full Text Available Abstract Background Progressive diversification of paralogs after gene expansion is essential to increase their functional specialization. However, mode and tempo of this divergence remain mostly unclear. Here we report the comparative analysis of PRDM genes, a family of putative transcriptional regulators involved in human tumorigenesis. Results Our analysis assessed that the PRDM genes originated in metazoans, expanded in vertebrates and further duplicated in primates. We experimentally showed that fast-evolving paralogs are poorly expressed, and that the most recent duplicates, such as primate-specific PRDM7, acquire tissue-specificity. PRDM7 underwent major structural rearrangements that decreased the number of encoded Zn-Fingers and modified gene splicing. Through internal duplication and activation of a non-canonical splice site (GC-AG, PRDM7 can acquire a novel intron. We also detected an alternative isoform that can retain the intron in the mature transcript and that is predominantly expressed in human melanocytes. Conclusion Our findings show that (a molecular evolution of paralogs correlates with their expression pattern; (b gene diversification is obtained through massive genomic rearrangements; and (c splicing modification contributes to the functional specialization of novel genes.

  1. Investigation of T-cell receptor-γ gene rearrangement in gastrointestinal lymphomas by PCR-SSCP analysis

    Institute of Scientific and Technical Information of China (English)

    Xi-Qun Han; Li He; Lan-Ying Shong; Hui-Yong Jiang; Mei-Gang Zhu; Tong Zhao

    2004-01-01

    AIM: To analyze the characterization of T-cell receptor-γ (TCR-γ) gene rearrangement in the gastrointestinal lymphomas and evaluate the value of PCR-SSCP analysis in gastrointestinal lymphomas investigation.METHODS: TCR-γgene rearrangement segments of gastrointestinal lymphomas were cloned and sequenced.Single clone plasmid and mixed clone plsamids were subsequently submitted to PCR-SSCP analysis to investigate the relationship between the number of amplified clones and band patterns of the amplified products. The PCR products of TCR-γgene rearrangement of 40 gastrointestinal lymphomas were electrophoresed on agarose gels and the positive cases on agarose gels were studied by SSCP analysis.RESULTS: The sequencing showed that TCR-γ gene rearrangement of the gastrointestinal lymphomas included functional gene and pseudogene with extensive variety in the junctional regions. In SSCP analysis, the number of the single-stranded bands was about two times of the number of amplified clones, and double-stranded band became broad with the increased number of the amplified clones. Thirteen of the 25 B-cell gastrointestinal lymphomas and 14 of the 15 gastrointestinal T-cell lymphomas were positive detected on agarose gel electrophoresis. Of the positive cases detected by SSCP analysis, 3 B-cell lymphomas and 13 T-cell lymphomas showed positive bands. The other cases showed only smears. The rearranged pattern included 13 monoallelic gene rearrangements and 3 biallelic or oligoclonal gene rearrangements.CONCLUSION: The pattern of TCR-γ, gene rearrangement in gastrointestinal lymphomas are similar to that of the nodular lymphomas. PCR-SSCP analysis for TCR-γ gene rearrangement can be applied both for adjuvant diagnosis of gastrointestinal lymphomas and analysis of the gene rearrangement pattern. The ratio of TCR-γ gene rearrangements occurred in T-cell gastrointestinal lymphomas is significantly higher than that in B-cell gastrointestinal lymphomas. The gene rearrangement

  2. Processes of fungal proteome evolution and gain of function: gene duplication and domain rearrangement

    International Nuclear Information System (INIS)

    During evolution, organisms have gained functional complexity mainly by modifying and improving existing functioning systems rather than creating new ones ab initio. Here we explore the interplay between two processes which during evolution have had major roles in the acquisition of new functions: gene duplication and protein domain rearrangements. We consider four possible evolutionary scenarios: gene families that have undergone none of these event types; only gene duplication; only domain rearrangement, or both events. We characterize each of the four evolutionary scenarios by functional attributes. Our analysis of ten fungal genomes indicates that at least for the fungi clade, species significantly appear to gain complexity by gene duplication accompanied by the expansion of existing domain architectures via rearrangements. We show that paralogs gaining new domain architectures via duplication tend to adopt new functions compared to paralogs that preserve their domain architectures. We conclude that evolution of protein families through gene duplication and domain rearrangement is correlated with their functional properties. We suggest that in general, new functions are acquired via the integration of gene duplication and domain rearrangements rather than each process acting independently

  3. Prevalence of chromosomal rearrangements involving non-ETS genes in prostate cancer

    DEFF Research Database (Denmark)

    Kluth, Martina; Galal, Rami; Krohn, Antje;

    2015-01-01

    Prostate cancer is characterized by structural rearrangements, most frequently including translocations between androgen-dependent genes and members of the ETS family of transcription factor like TMPRSS2:ERG. In a recent whole genome sequencing study we identified 140 gene fusions that were...

  4. Rapid, Nonradioactive Detection of Clonal T-Cell Receptor Gene Rearrangements in Lymphoid Neoplasms

    Science.gov (United States)

    Bourguin, Anne; Tung, Rosann; Galili, Naomi; Sklar, Jeffrey

    1990-11-01

    Southern blot hybridization analysis of clonal antigen receptor gene rearrangements has proved to be a valuable adjunct to conventional methods for diagnosing lymphoid neoplasia. However, Southern blot analysis suffers from a number of technical disadvantages, including the time necessary to obtain results, the use of radioactivity, and the susceptibility of the method to various artifacts. We have investigated an alternative approach for assessing the clonality of antigen receptor gene rearrangements in lymphoid tissue biopsy specimens. This approach involves the amplification of rearranged γ T-cell receptor genes by the polymerase chain reaction and analysis of the polymerase chain reaction products by denaturing gradient gel electrophoresis. By use of this approach, clonal rearrangements from neoplastic lymphocytes constituting as little as 0.1-1% of the total cells in the tissue are detected as discrete bands in the denaturing gel after the gel is stained with ethidium bromide and viewed under ultraviolet light. In contrast, polyclonal rearrangements from reactive lymphocytes appear as a diffuse smear along the length of the gel. Our findings suggest that polymerase chain reaction combined with denaturing gradient gel electrophoresis may offer a rapid, nonradioactive, and sensitive alternative to Southern blot analysis for the diagnostic evaluation of lymphoid tissue biopsy specimens.

  5. [Analyses of the rearrangement of T-cell receptor- and immunoglobulin genes in the diagnosis of lymphoproliferative disorders].

    Science.gov (United States)

    Griesser, D H

    1995-01-01

    Rearrangements are developmentally regulated genetic recombinations in T and B cells which generate functional T cell receptor (TcR) and immunoglobulin genes, respectively. Different variable, sometimes diversity, and joining gene segments which are discontinuously spread out within their chromosomal location in germline configuration, are randomly assembled in individual lymphocytes. These rearrangements can be detected by Southern Blot analysis if more than 5% of a total lymphocyte population in a biopsy specimen carries the same clonal rearrangement. We analyzed DNA from 324 snap-frozen biopsy specimens from lympho-proliferative disorders. None of the 20 reactive lesions and four malignant myelomonocytic tumors had a clonal antigen receptor gene rearrangement. All 117 malignant B cell lymphomas of different subtypes and 95 of 97 malignant T cell lymphomas showed a clonal gene rearrangement. Only two angioimmunoblastic lymphadenopathy(AILD)-type T cell lymphomas did not have immune receptor gene rearrangements. They were morphologically indistinguishable from the other 47 T/AILD lymphomas with clonal rearrangement patterns. In most cases TcR beta and immunoglobulin heavy chain (IgH) gene probes were sufficient for lineage assignment of the clonal T or B lymphocyte population. In 18% of B lymphomas, however, a cross-lineage rearrangement of TcR beta genes, and in 20% of the T cell lymphomas a clonal IgH gene rearrangement was detected. After exclusion of centrocytic, large cell anaplastic lymphomas (LCAL) of B-type, and T/AILD lymphomas which are overrepresented in our study, only 10% of the remaining 147 T and B cell lymphomas had aberrant rearrangements. TcR rearrangements other than those of the beta chain genes were extremely rare in B cell lymphomas, as were Ig kappa rearrangements in T lymphomas. Only two T/AILD lymphomas had IgH and Ig kappa rearrangement in addition to their clonal T cell receptor gene rearrangements. Both samples likely contain a clonal B

  6. Immunoglobulin gene expression and regulation of rearrangement in kappa transgenic mice

    Energy Technology Data Exchange (ETDEWEB)

    Ritchie, K.A.

    1986-01-01

    Transgenic mice were produced by microinjection of the functionally rearranged immunoglobulin kappa gene from the myeloma MOPC-21 into the male pronucleus of fertilized mouse eggs, and implantation of the microinjected embryos into foster mothers. Mice that integrated the injected gene were detected by hybridizing tail DNA dots with radioactively labelled pBR322 plasmid DNA, which detects pBR322 sequences left as a tag on the microinjected DNA. Mice that integrated the injected gene (six males) were mated and the DNA, RNA and serum kappa chains of their offspring were analyzed. A rabbit anti-mouse kappa chain antiserum was also produced for use in detection of mouse kappa chains on protein blots. Hybridomas were produced from the spleen cells of these kappa transgenic mice to immortalize representative B cells and to investigate expression of the transgenic kappa gene, its effect on allelic exclusion, and its effect on the control of light chain gene rearrangement and expression. The results show that the microinjected DNA is integrated as concatamers in unique single or, rarely, two separate sites in the genome. The concatamers are composed of several copies (16 to 64) of injected DNA arranged in a head to tail fashion. The transgene is expressed into protein normally and in a tissue specific fashion. For the first time in these transgenic mice, all tissues contain a functionally rearranged and potentially expressible immunoglobulin gene. The transgene is expressed only in B cells and not in hepatocytes, for example. This indicates that rearrangement of immunoglobulin genes is necessary but not sufficient for the tissue specific expression of these genes by B cells.

  7. Cytosine arabinoside-metabolizing enzyme genes are underexpressed in children with MLL gene-rearranged acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    J.F. Mata

    2006-11-01

    Full Text Available Infant acute lymphoblastic leukemia (IALL is characterized by mixed lineage leukemia (MLL gene rearrangements, unique gene expression profiles, poor prognosis, and drug resistance. One exception is cytosine arabinoside (Ara-C to which IALL cells seem to be more sensitive. We quantified mRNA expression of Ara-C key enzymes in leukemic lymphoblasts from 64 Brazilian ALL children, 15 of them presenting MLL gene rearrangement, and correlated it with clinical and biological features. The diagnosis was based on morphological criteria and immunophenotyping using monoclonal antibodies. MLL gene rearrangements were detected by conventional cytogenetic analysis, RT-PCR and/or fluorescence in situ hybridization. The DCK and HENT1 expression levels were determined by real-time quantitative PCR using SYBR Green I. Relative quantification was made by the standard curve method. The results were analyzed by Mann-Whitney and Fisher exact tests. A P value of £0.05 was considered to be statistically significant. DCK and HENT1 expression levels were significantly lower in children with MLL gene-rearranged ALL compared to children with MLL germ line ALL (P = 0.0003 and 0.03, respectively. Our results differ from previous ones concerning HENT1 mRNA expression that observed a higher expression level in MLL gene-rearranged leukemias. In conclusion, the expression of the genes related to Ara-C metabolism was lower in MLL-positive children in the sample studied, suggesting the presence of population differences in the expression profile of these genes especially for HENT1.

  8. Color bar coding the BRCA1 gene on combed DNA: a useful strategy for detecting large gene rearrangements.

    Science.gov (United States)

    Gad, S; Aurias, A; Puget, N; Mairal, A; Schurra, C; Montagna, M; Pages, S; Caux, V; Mazoyer, S; Bensimon, A; Stoppa-Lyonnet, D

    2001-05-01

    Genetic linkage data have shown that alterations of the BRCA1 gene are responsible for the majority of hereditary breast and ovarian cancers. BRCA1 germline mutations, however, are found less frequently than expected. Mutation detection strategies, which are generally based on the polymerase chain reaction, therefore focus on point and small gene alterations. These approaches do not allow for the detection of large gene rearrangements, which also can be involved in BRCA1 alterations. Indeed, a few of them, spread over the entire BRCA1 gene, have been detected recently by Southern blotting or transcript analysis. We have developed an alternative strategy allowing a panoramic view of the BRCA1 gene, based on dynamic molecular combing and the design of a full four-color bar code of the BRCA1 region. The strategy was tested with the study of four large BRCA1 rearrangements previously reported. In addition, when screening a series of 10 breast and ovarian cancer families negatively tested for point mutation in BRCA1/2, we found an unreported 17-kb BRCA1 duplication encompassing exons 3 to 8. The detection of rearrangements as small as 2 to 6 kb with respect to the normal size of the studied fragment is achieved when the BRCA1 region is divided into 10 fragments. In addition, as the BRCA1 bar code is a morphologic approach, the direct observation of complex and likely underreported rearrangements, such as inversions and insertions, becomes possible. PMID:11284038

  9. The evolution of vertebrate somatostatin receptors and their gene regions involves extensive chromosomal rearrangements

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    Ocampo Daza Daniel

    2012-11-01

    Full Text Available Abstract Background Somatostatin and its related neuroendocrine peptides have a wide variety of physiological functions that are mediated by five somatostatin receptors with gene names SSTR1-5 in mammals. To resolve their evolution in vertebrates we have investigated the SSTR genes and a large number of adjacent gene families by phylogeny and conserved synteny analyses in a broad range of vertebrate species. Results We find that the SSTRs form two families that belong to distinct paralogons. We observe not only chromosomal similarities reflecting the paralogy relationships between the SSTR-bearing chromosome regions, but also extensive rearrangements between these regions in teleost fish genomes, including fusions and translocations followed by reshuffling through intrachromosomal rearrangements. These events obscure the paralogy relationships but are still tractable thanks to the many genomes now available. We have identified a previously unrecognized SSTR subtype, SSTR6, previously misidentified as either SSTR1 or SSTR4. Conclusions Two ancestral SSTR-bearing chromosome regions were duplicated in the two basal vertebrate tetraploidizations (2R. One of these ancestral SSTR genes generated SSTR2, -3 and -5, the other gave rise to SSTR1, -4 and -6. Subsequently SSTR6 was lost in tetrapods and SSTR4 in teleosts. Our study shows that extensive chromosomal rearrangements have taken place between related chromosome regions in teleosts, but that these events can be resolved by investigating several distantly related species.

  10. Analysis of rearranged immunoglobulin genes indicating a process of clonal evolution in chronic lymphocytic leukaemia.

    Science.gov (United States)

    Hakim, I; Rechavi, G; Brok-Simoni, F; Grossman, Z; Amariglio, N; Mandel, M; Ramot, B; Ben-Bassat, I; Katzir, N

    1993-07-01

    Chronic lymphocytic leukaemia (CLL) is known to be a stable monoclonal neoplasm. In contrast to early studies demonstrating no more than two hybridizing immunoglobulin heavy chain bands corresponding to the two expected alleles, we have demonstrated an unexpected multiband pattern when the HindIII-digested DNA samples from 38 CLL patients were analysed by Southern blot hybridization using JH and C mu gene probes. In order to characterize the genetic basis for the multiband pattern, we molecularly cloned the immunoglobulin heavy chain genes of one of the patients whose leukaemic DNA sample demonstrated three hybridizing JH bands and a loss of the germline band. The cloned rearranged immunoglobulin genes could be divided, based on the restriction mapping and the hybridization with the various probes, into two basic patterns representing two alleles. In one of the cloned rearranged immunoglobulin genes a secondary rearrangement occurred that resulted in the addition of 300 base-pair long sequence into the switch region, and the creation of a HindIII restriction site. The results of the study suggest that clonal evolution occurs in some CLL, and that many of these neoplasms are indeed oligoclonal due to the accumulation of secondary genetic changes.

  11. Analysis of VH gene rearrangement and somatic hypermutation in type 1 autoimmune pancreatitis.

    Science.gov (United States)

    Okumura, Fumihiro; Sakuma, Hidenori; Nakazawa, Takahiro; Hayashi, Kazuki; Naitoh, Itaru; Miyabe, Katsuyuki; Yoshida, Michihiro; Yamashita, Hiroaki; Ohara, Hirotaka; Inagaki, Hiroshi; Joh, Takashi

    2012-05-01

    Type 1 autoimmune pancreatitis (AIP) is the pancreatic manifestation of systemic fibroinflammatory disease called immunoglobulin G4-associated systemic disease. Although this inflammatory process is considered to be a disease with an autoimmune mechanism, its pathogenesis still remains unclear. To clarify the characteristics of B cells infiltrating the lesion, we analyzed the immunoglobulin heavy chain variable region (VH) gene rearrangement and somatic hypermutation of invasive lymphoid cells in type 1 AIP (n= 3), in comparison with obstructive pancreatitis (n= 3) as a control. DNA was extracted from the affected inflammatory lesions. After PCR amplification of the rearranged VH gene, the clones were subcloned, and recombinant clones were randomly selected and sequenced. More than 60 clones per case were analyzed. Monoclonal VH rearrangement was not detected in any of the cases examined. There was no VH family or VH fragment specific to type 1 AIP and obstructive pancreatitis. However, the rate of unmutated VH fragments in type 1 AIP (17%) was higher than that in obstructive pancreatitis (5.1%) (P= 0.010). Our study suggests that an increased rate of unmutated or less mutated VH genes may be characteristic of type 1 AIP and might play a role in the development of this disease.

  12. Clonal rearrangements of immunoglobulin genes and progression to B cell lymphoma in cutaneous lymphoid hyperplasia.

    Science.gov (United States)

    Wood, G S; Ngan, B Y; Tung, R; Hoffman, T E; Abel, E A; Hoppe, R T; Warnke, R A; Cleary, M L; Sklar, J

    1989-07-01

    Cutaneous lymphoid hyperplasia (CLH) is a disorder characterized by the development of one or more skin lesions containing dense lymphoid infiltrates that exhibit the histopathologic features of a benign, reactive process. Nevertheless, some cases have been associated with the subsequent development of clinically overt lymphomas. This suggests that monoclonal populations may exist in some cases of CLH and that these cases may represent a subset more likely to evolve into lymphoma. To determine if such a subset of CLH can be distinguished, Southern blot analysis of DNA was used to study the immunogenotypic features of lesions from 14 patients with clinical, histopathologic, and immunopathologic findings characteristic of CLH. Five cases exhibited detectable clonal rearrangements of immunoglobulin genes. Furthermore, one of these five cases evolved into overt diffuse large cell lymphoma of B cell lineage during a 2-year follow-up of recurrent disease at the original cutaneous site. The immunoglobulin gene rearrangements of this lymphoma were identical to those of the prior CLH lesion. There was no evidence of detectable t(14;18) chromosomal translocations or clonal rearrangements of the beta gene of the T cell receptor in any case. It was concluded that CLH can be divided into two subsets based on the presence or absence of a clonal B cell population, and that overt lymphoma can arise from the former subset and contain the same B cell clone identified in the pre-existent CLH lesion.

  13. Specific amplification by PCR of rearranged genomic variable regions of immunoglobulin genes from mouse hybridoma cells.

    Science.gov (United States)

    Berdoz, J; Monath, T P; Kraehenbuhl, J P

    1995-04-01

    We have designed a novel strategy for the isolation of the rearranged genomic fragments encoding the L-VH-D-JH and L-V kappa/lambda-J kappa/lambda regions of mouse immunoglobulin genes. This strategy is based on the PCR amplification of genomic DNA from mouse hybridomas using multiple specific primers chosen in the 5'-untranslated region and in the intron downstream of the rearranged JH/J kappa/lambda sequences. Variable regions with intact coding sequences, including full-length leader peptides (L) can be obtained without previous DNA sequencing. Our strategy is based on a genomic template that produces fragments that do not need to be adapted for recombinant antibody expression, thus facilitating the generation of chimeric and isotype-switched immunoglobulins.

  14. Gene conversion-like events in the diversification of human rearranged IGHV3-23*01 gene sequences

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    Bhargavi eDuvvuri

    2012-06-01

    Full Text Available Gene conversion (GCV as a mechanism of immunoglobulin diversification is well established in a few species. However, definitive evidence of GCV-like events in human immunoglobulin genes is scarce. GCV is mediated by activation-induced cytidine deaminase (AID. The lack of evidence of GCV in human rearranged immunoglobulin gene sequences is puzzling given the presence of highly similar germline donors and all the enzymatic machinery required for GCV. In this study, we undertook a computational analysis of rearranged IGHV3-23*01 gene sequences from common variable immunodeficiency (CVID patients and healthy individuals to survey ‘GCV-like’ activities. Our search identified strong evidence of GCV-like patterns. Germline VH sequences were identified as potential donors for clustered mutations in rearranged IGHV3-23*01 gene sequences. We identified minimum and maximum sequence identities between donor and recipient sequences that can serve as targets for GCV and our findings are consistent with those reported in literature. We observed that GCV-like tracts are flanked by activation-induced cytidine deaminase (AID hotspot motifs. Structural modeling of IGHV3-23*01 gene sequence revealed that hypermutable bases flanking GCV-like tracts, are in the single stranded DNA (ssDNA of stable stem-loop structures (SLSs. SsDNA is inherently fragile and also an optimal target for AID. We speculate that GCV could have been initiated by the targeting of hypermutable bases in ssDNA state in stable SLSs, plausibly by AID. We have observed that the frequency of GCV-like events is significantly higher in rearranged IGHV323-*01 sequences from healthy individuals compared to that of CVID patients. GCV, unlike SHM, can result in multiple base substitutions that can alter many amino acids. The extensive changes in antibody affinity by GCV-like events, as identified in this study would be instrumental in protecting humans against pathogens that diversify their genome by

  15. Characterization of gene rearrangements resulted from genomic structural aberrations in human esophageal squamous cell carcinoma KYSE150 cells.

    Science.gov (United States)

    Hao, Jia-Jie; Gong, Ting; Zhang, Yu; Shi, Zhi-Zhou; Xu, Xin; Dong, Jin-Tang; Zhan, Qi-Min; Fu, Song-Bin; Wang, Ming-Rong

    2013-01-15

    Chromosomal rearrangements and involved genes have been reported to play important roles in the development and progression of human malignancies. But the gene rearrangements in esophageal squamous cell carcinoma (ESCC) remain to be identified. In the present study, array-based comparative genomic hybridization (array-CGH) was performed on the ESCC cell line KYSE150. Eight disrupted genes were detected according to the obviously distinct unbalanced breakpoints. The splitting of these genes was validated by dual-color fluorescence in-situ hybridization (FISH). By using rapid amplification of cDNA ends (RACE), genome walking and sequencing analysis, we further identified gene disruptions and rearrangements. A fusion transcript DTL-1q42.2 was derived from an intrachromosomal rearrangement of chromosome 1. Highly amplified segments of DTL and PTPRD were self-rearranged. The sequences on either side of the junctions possess micro-homology with each other. FISH results indicated that the split DTL and PTPRD were also involved in comprising parts of the derivative chromosomes resulted from t(1q;9p;12p) and t(9;1;9). Further, we found that regions harboring DTL (1q32.3) and PTPRD (9p23) were also splitting in ESCC tumors. The data supplement significant information on the existing genetic background of KYSE150, which may be used as a model for studying these gene rearrangements.

  16. Bcl-2 GENE REARRANGEMENT DETERMINED BY PCR AS A MEAN TO DETECT MINIMAL RESIDUAL DISEASE IN MALIGNANT LYMPHOMAS

    Institute of Scientific and Technical Information of China (English)

    XIANG Zhi-fu; LU Yu-ying; LAI Yong-rong; CHEN Yan; LI Hui-yu; ZOU Ping

    1999-01-01

    Objective: To develop a sensitive method to detect minimal residual disease and to elucidate the significance of bcl-2 gene rearrangement in diagnosis and treatment of malignant lymphoma. Methods: Using polymerase chain reaction (PCR) to detect bcl-2 gene rearrangement and using serial dilution method to define the sensitivity of PCR. Results: In 9 different malignant lymphoma cell lines, Su-DHL-4 and Su-DHL-6 were shown bcl-2(MBR)/JH rearrangement, the sensitivity of PCR was 1:105. In 16 patients with follicular lymphoma, the peripheral blood and bone marrow were PCR positive in 4 cases both at initial diagnosis and after complete remission. Conclusion:Detection of bcl-2 gene rearrangement by PCR provides a sensitive and specific assay of minimal residual disease.It is helpful to improve staging of disease, prognosis and evaluation of the treatment results.

  17. Large genomic rearrangement of BRCA1 and BRCA2 genes in familial breast cancer patients in Korea.

    Science.gov (United States)

    Cho, Ja Young; Cho, Dae-Yeon; Ahn, Sei Hyun; Choi, Su-Youn; Shin, Inkyung; Park, Hyun Gyu; Lee, Jong Won; Kim, Hee Jeong; Yu, Jong Han; Ko, Beom Seok; Ku, Bo Kyung; Son, Byung Ho

    2014-06-01

    We screened large genomic rearrangements of the BRCA1 and BRCA2 genes in Korean, familial breast cancer patients. Multiplex ligation-dependent probe amplification assay was used to identify BRCA1 and BRCA2 genomic rearrangements in 226 Korean familial breast cancer patients with risk factors for BRCA1 and BRCA2 mutations, who previously tested negative for point mutations in the two genes. We identified only one large deletion (c.4186-1593_4676-1465del) in BRCA1. No large rearrangements were found in BRCA2. Our result indicates that large genomic rearrangement in the BRCA1 and BRCA2 genes does not seem like a major determinant of breast cancer susceptibility in the Korean population. A large-scale study needs to validate our result in Korea.

  18. Human ETS2 gene on chromosome 21 is not rearranged in Alzheimer disease

    Energy Technology Data Exchange (ETDEWEB)

    Sacchi, N.; Nalbantoglu, J.; Sergovich, F.R.; Papas, T.S. (National Cancer Institute, Frederick, MD (USA))

    1988-10-01

    The human ETS2 gene, a member of the ETS gene family, with sequence homology with the retroviral ets sequence of the avian erythroblastosis retrovirus E26 is located on chromosome 21. Molecular genetic analysis of Down syndrome (DS) patients with partial trisomy 21 allowed us to reinforce the supposition that ETS2 may be a gene of the minimal DS genetic region. It was originally proposed that a duplication of a portion of the DS region represents the genetic basis of Alzheimer disease, a condition associated also with DS. No evidence of either rearrangements or duplications of ETS2 could be detected in DNA from fibroblasts and brain tissue of Alzheimer disease patients with either the sporadic or the familiar form of the disease. Thus, an altered ETS2 gene dosage does not seem to be a genetic cause or component of Alzheimer disease.

  19. Complete nucleotide sequence and gene rearrangement of the mitochondrial genome of Occidozyga martensii

    Indian Academy of Sciences (India)

    En Li; Xiaoqiang Li; Xiaobing Wu; Ge Feng; Man Zhang; Haitao Shi; Lijun Wang; Jianping Jiang

    2014-12-01

    In this study, the complete nucleotide sequence (18,321 bp) of the mitochondrial (mt) genome of the round-tongued floating frog, Occidozyga martensii was determined. Although, the base composition and codon usage of O. martensii conformed to the typical vertebrate patterns, this mt genome contained 23 tRNAs (a tandem duplication of tRNA-Met gene). The LTPF tRNA-gene cluster, and the derived position of the ND5 gene downstream of the control region, were present in this mitogenome. Moreover, we found that in the WANCY tRNA-gene cluster, the tRNA-Asn gene was located between the tRNA-Tyr and COI genes instead of between the tRNA-Ala and tRNA-Cys genes, which is a novel mtDNA gene rearrangement in vertebrates. Based on the concatenated nucleotide sequences of the 13 protein-coding genes, phylogenetic analysis (BI, ML, MP) was performed to further clarify the phylogenetic relations of this species within anurans.

  20. Sessile snails, dynamic genomes: gene rearrangements within the mitochondrial genome of a family of caenogastropod molluscs

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    Bieler Rüdiger

    2010-07-01

    Full Text Available Abstract Background Widespread sampling of vertebrates, which comprise the majority of published animal mitochondrial genomes, has led to the view that mitochondrial gene rearrangements are relatively rare, and that gene orders are typically stable across major taxonomic groups. In contrast, more limited sampling within the Phylum Mollusca has revealed an unusually high number of gene order arrangements. Here we provide evidence that the lability of the molluscan mitochondrial genome extends to the family level by describing extensive gene order changes that have occurred within the Vermetidae, a family of sessile marine gastropods that radiated from a basal caenogastropod stock during the Cenozoic Era. Results Major mitochondrial gene rearrangements have occurred within this family at a scale unexpected for such an evolutionarily young group and unprecedented for any caenogastropod examined to date. We determined the complete mitochondrial genomes of four species (Dendropoma maximum, D. gregarium, Eualetes tulipa, and Thylacodes squamigerus and the partial mitochondrial genomes of two others (Vermetus erectus and Thylaeodus sp.. Each of the six vermetid gastropods assayed possessed a unique gene order. In addition to the typical mitochondrial genome complement of 37 genes, additional tRNA genes were evident in D. gregarium (trnK and Thylacodes squamigerus (trnV, trnLUUR. Three pseudogenes and additional tRNAs found within the genome of Thylacodes squamigerus provide evidence of a past duplication event in this taxon. Likewise, high sequence similarities between isoaccepting leucine tRNAs in Thylacodes, Eualetes, and Thylaeodus suggest that tRNA remolding has been rife within this family. While vermetids exhibit gene arrangements diagnostic of this family, they also share arrangements with littorinimorph caenogastropods, with which they have been linked based on sperm morphology and primary sequence-based phylogenies. Conclusions We have

  1. Mitochondrial genomes of praying mantises (Dictyoptera, Mantodea): rearrangement, duplication, and reassignment of tRNA genes.

    Science.gov (United States)

    Ye, Fei; Lan, Xu-E; Zhu, Wen-Bo; You, Ping

    2016-01-01

    Insect mitochondrial genomes (mitogenomes) contain a conserved set of 37 genes for an extensive diversity of lineages. Previously reported dictyopteran mitogenomes share this conserved mitochondrial gene arrangement, although surprisingly little is known about the mitogenome of Mantodea. We sequenced eight mantodean mitogenomes including the first representatives of two families: Hymenopodidae and Liturgusidae. Only two of these genomes retain the typical insect gene arrangement. In three Liturgusidae species, the trnM genes have translocated. Four species of mantis (Creobroter gemmata, Mantis religiosa, Statilia sp., and Theopompa sp.-HN) have multiple identical tandem duplication of trnR, and Statilia sp. additionally includes five extra duplicate trnW. These extra trnR and trnW in Statilia sp. are erratically arranged and form another novel gene order. Interestingly, the extra trnW is converted from trnR by the process of point mutation at anticodon, which is the first case of tRNA reassignment for an insect. Furthermore, no significant differences were observed amongst mantodean mitogenomes with variable copies of tRNA according to comparative analysis of codon usage. Combined with phylogenetic analysis, the characteristics of tRNA only possess limited phylogenetic information in this research. Nevertheless, these features of gene rearrangement, duplication, and reassignment provide valuable information toward understanding mitogenome evolution in insects. PMID:27157299

  2. Rearrangement of RAG-1 recombinase gene in radiation-sensitive ''wasted'' mice

    International Nuclear Information System (INIS)

    The recent cloning and characterization of recombinase genes (RAG- 1/RAG-2) expressed in lymphoid and possibly central nervous system tissues prompted us to examine expression of these genes in DNA repair-deficient/immunodeficient wasted mice (wst). Our results revealed expression of RAG-1 mRNA was detected in spinal cord or brain from wst/wst mice or their normal littermates (wst/sm-bullet mice). In thymus tissue, a small RAG-1 transcript was detected in wst/wst mice that was not evident in thymus from control mice. In wst/lg-bullet mice, a two-fold increase in RAG-1 mRNA was evident in thymus tissue. RAG-2 mRNA could only be detected in thymus tissue from wst/sm-bullet and not from wst;/wst or parental control BCF1 mice. Southern blots revealed a rearrangement/deletion within the RAG-1 gene of affected wasted mice, not evident in known strain-specific parental or littermate controls. These results support the idea that the RAG-1 gene may map at or near the locus for the wasted mutation. In addition, they suggest the importance of recombinase function in normal immune and central nervous system development as well as the potential contribution of this gene family to the normal repair of radiation-induced DNA damage

  3. Evolution of the mitochondrial genome in snakes: Gene rearrangements and phylogenetic relationships

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    Zhou Kaiya

    2008-11-01

    Full Text Available Abstract Background Snakes as a major reptile group display a variety of morphological characteristics pertaining to their diverse behaviours. Despite abundant analyses of morphological characters, molecular studies using mitochondrial and nuclear genes are limited. As a result, the phylogeny of snakes remains controversial. Previous studies on mitochondrial genomes of snakes have demonstrated duplication of the control region and translocation of trnL to be two notable features of the alethinophidian (all serpents except blindsnakes and threadsnakes mtDNAs. Our purpose is to further investigate the gene organizations, evolution of the snake mitochondrial genome, and phylogenetic relationships among several major snake families. Results The mitochondrial genomes were sequenced for four taxa representing four different families, and each had a different gene arrangement. Comparative analyses with other snake mitochondrial genomes allowed us to summarize six types of mitochondrial gene arrangement in snakes. Phylogenetic reconstruction with commonly used methods of phylogenetic inference (BI, ML, MP, NJ arrived at a similar topology, which was used to reconstruct the evolution of mitochondrial gene arrangements in snakes. Conclusion The phylogenetic relationships among the major families of snakes are in accordance with the mitochondrial genomes in terms of gene arrangements. The gene arrangement in Ramphotyphlops braminus mtDNA is inferred to be ancestral for snakes. After the divergence of the early Ramphotyphlops lineage, three types of rearrangements occurred. These changes involve translocations within the IQM tRNA gene cluster and the duplication of the CR. All phylogenetic methods support the placement of Enhydris plumbea outside of the (Colubridae + Elapidae cluster, providing mitochondrial genomic evidence for the familial rank of Homalopsidae.

  4. Infectious bronchitis viruses with naturally occurring genomic rearrangement and gene deletion.

    Science.gov (United States)

    Hewson, Kylie A; Ignjatovic, Jagoda; Browning, Glenn F; Devlin, Joanne M; Noormohammadi, Amir H

    2011-02-01

    Infectious bronchitis viruses (IBVs) are group III coronaviruses that infect poultry worldwide. Genetic variations, including whole-gene deletions, are key to IBV evolution. Australian subgroup 2 IBVs contain sequence insertions and multiple gene deletions that have resulted in a substantial genomic divergence from international IBVs. The genomic variations present in Australian IBVs were investigated and compared to those of another group III coronavirus, turkey coronavirus (TCoV). Open reading frames (ORFs) found throughout the genome of Australian IBVs were analogous in sequence and position to TCoV ORFs, except for ORF 4b, which appeared to be translocated to a different position in the subgroup 2 strains. Subgroup 2 strains were previously reported to lack genes 3a, 3b and 5a, with some also lacking 5b. Of these, however, genes 3b and 5b were found to be present but contained various mutations that may affect transcription. In this study, it was found that subgroup 2 IBVs have undergone a more substantial genomic rearrangements than previously thought.

  5. Rearrangement and junctional-site sequence analyses of T-cell receptor gamma genes in intestinal intraepithelial lymphocytes from murine athymic chimeras.

    Science.gov (United States)

    Whetsell, M; Mosley, R L; Whetsell, L; Schaefer, F V; Miller, K S; Klein, J R

    1991-12-01

    The molecular organization of rearranged T-cell receptor (TCR) gamma genes intraepithelial lymphocytes (IEL) was studied in athymic radiation chimeras and was compared with the organization of gamma gene rearrangements in IEL from thymus-bearing animals by polymerase chain reaction and by sequence analyses of DNA spanning the junction of the variable (V) and joining (J) genes. In both thymus-bearing mice and athymic chimeras, IEL V-J gamma-gene rearrangements occurred for V gamma 1.2, V gamma 2, and V gamma 5 but not for V gamma 3 or V gamma 4. Sequence analyses of cloned V-J polymerase chain reaction-amplified products indicated that in both thymus-bearing mice and athymic chimeras, rearrangement of V gamma 1.2 and V gamma 5 resulted in in-frame as well as out-of-frame genes, whereas nearly all V gamma 2 rearrangements were out of frame from either type of animal. V-segment nucleotide removal occurred in most V gamma 1.2, V gamma 2, and V gamma 5 rearrangements; J-segment nucleotide removal was common in V gamma 1.2 but not in V gamma 2 or V gamma 5 rearrangements. N-segment nucleotide insertions were present in V gamma 1.2, V gamma 2, and V gamma 5 IEL rearrangements in both thymus-bearing mice and athymic chimeras, resulting in a predominant in-frame sequence for V gamma 5 and a predominant out-of-frame sequence for V gamma 2 genes. These findings demonstrate that (i) TCR gamma-gene rearrangement occurs extrathymically in IEL, (ii) rearrangements of TCR gamma genes involve the same V gene regardless of thymus influence; and (iii) the thymus does not determine the degree to which functional or nonfunctional rearrangements occur in IEL.

  6. Mitochondrial genomes of four katydids (Orthoptera: Phaneropteridae): New gene rearrangements and their phylogenetic implications.

    Science.gov (United States)

    Yang, Jing; Ye, Fei; Huang, Yuan

    2016-01-10

    Phaneropteridae is a family of Orthoptera that displays an amazing amount of diversity in terms of both forms and species. We sequenced the mitochondrial genomes (mitogenomes) of two bush katydids: Ruidocollaris obscura and Kuwayamaea brachyptera (Phaneropterinae), and two true katydids: Orophyllus montanus and Phyllomimus detersus (Pseudophyllinae), to obtain further insight into the characteristics of the katydid mitogenomes and to investigate the taxonomic status of subfamily Pseudophyllinae and the diversity of gene arrangements among Phaneropteridae. The following general genomic characteristics were observed in the four katydids: a longer length of the mitogenomes (16,007bp-16,667bp) compared with Caelifera, abundant intergenic spacers, and accepted atypical initiation codons (GTG and TTG, found in cox1, nad1 and nad2). A new orientation of the gene arrangement "trnM-trnI-trnQ" was identified in P. detersus, which is the first representative of Polyneoptera found to carry this gene cluster. Large identical fragments (492bp) were detected in control region 1 (CR1) and control region 2 (CR2) of R. obscura. The high similarity of the duplicated CRs is likely due to a recent gene duplication or concerted evolution. Analyses of the duplicated CRs revealed one conserved stem-loop (on the N-strand) located in the identical sequences of both CRs that might be linked to replication initiation. Phylogenetic analyses based on 13 protein-coding genes and 2 ribosomal RNA genes from 20 Ensiferan species yielded the identical topologies between two different methods (maximum likelihood and bayesian inference). The newly sequenced Pseudophyllinae species was placed as the sister group of Phaneropterinae, and Mecopodinae clustered with Pseudophyllinae+Phaneropterinae. Additionally, we speculate that the species in Ruidocollaris and Sinochlora, as well as their closely related genera, may have undergone numerous rearrangement events. PMID:26410415

  7. Rearrangement of RAG-1 recombinase gene in radiation-sensitive ''wasted'' mice

    International Nuclear Information System (INIS)

    Mice recessive for the autosomal gene ''wasted'' (wst) display a disease pattern which includes increased sensitivity to the killing effects of ionizing radiation, immunodeficiency, and neurologic dysfunction. The recent cloning and characterization of recombinase genes (RAG-1/RAG-2) expressed in lymphoid and possibly central nervous system tissues prompted us to examine expression of these genes in DNA repair-deficient/immunodeficient wasted mice. Our results revealed expression of RAG-1 mRNA in spinal cord (but not brain) of control mice; no expression of RAG-1 mRNA was detected in spinal cord or brain from wst/wst mice or their normal littermates (wst/· mice). In thymus tissue, a small RAG-1 transcript (1.0 kb) was detected in wst/wst mice that was not evident in thymus from control mice. In wst/· mice, a two-fold increase in RAG-1 MRNA was evident in thymus tissue. RAG-2 mRNA could only be detected in thymus tissue from wst/· and not from wst/wst or parental control BCF1 mice. Southern blots revealed a rearrangement/deletion within the RAG-1 gene of affected wasted mice, not evident in known strain-specific parental or littermate controls. These results support the idea that the RAG-1 gene may map at or near the locus for the wasted mutation. In addition, they suggest the importance of recombinase function in normal immune and central nervous system development as well as the potential contribution of this gene family to the normal repair of radiation-induced DNA damage

  8. Rearrangement of RAG-1 recombinase gene in DNA-repair deficient ``wasted`` mice

    Energy Technology Data Exchange (ETDEWEB)

    Woloschak, G.E.; Libertin, C.R.; Weaver, P. [Loyola Univ., Chicago, IL (United States); Churchill, M.; Chang-Liu, C.M. [Argonne National Lab., IL (United States)

    1993-11-01

    Mice recessive for the autosomal gene ``wasted`` wst display a disease pattern which includes increased sensitivity to the killing effects of ionizing radiation, immunodeficiency, and neurologic dysfunction. The recent cloning and characterization of recombinase genes (RAG-l/RAG-2) expressed in lymphoid and possibly central nervous system tissues prompted us to examine expression of these genes in DNA repair-deficient/immunodeficient wasted mice. Our results revealed expression of RAG-1 mRNA in spinal cord (but not brain) of control mice; no expression of RAG-1 mRNA was detected in spinal cord or brain from wst/wst mice or their normal littermates (wst/{center_dot}mice). In thymus tissue, a small RAG-1 transcript (1.0 kb) was detected in wst/wst mice that was not evident in thymus from control mice. In wst/{center_dot}mice, a two-fold increase in RAG-1 mRNA was evident in thymus tissue. RAG-2 mRNA could only be detected in thymus tissue from wst/{center_dot} and not from wst/wst or parental control BCF{sub 1} mice. Southern blots revealed a rearrangement/deletion within the RAG-1 gene of affected wasted mice, not evident in known strain-specific parental or littermate controls. These results support the idea that the RAG-1 gene may map at or near the locus for the wasted mutation. In addition, they suggest the importance of recombinase function in normal immune and central nervous system development as well as the potential contribution of this gene family to the normal repair of radiation-induced DNA damage.

  9. Rearrangement of RAG-1 recombinase gene in radiation-sensitive ``wasted`` mice

    Energy Technology Data Exchange (ETDEWEB)

    Woloschak, G.E. [Argonne National Lab., IL (United States)]|[Loyola Univ., Maywood, IL (United States); Libertin, C.R.; Weaver, P. [Loyola Univ., Maywood, IL (United States); Churchill, M.; Chang-Liu, C.M. [Argonne National Lab., IL (United States)

    1993-09-01

    Mice recessive for the autosomal gene ``wasted`` (wst) display a disease pattern which includes increased sensitivity to the killing effects of ionizing radiation, immunodeficiency, and neurologic dysfunction. The recent cloning and characterization of recombinase genes (RAG-1/RAG-2) expressed in lymphoid and possibly central nervous system tissues prompted us to examine expression of these genes in DNA repair-deficient/immunodeficient wasted mice. Our results revealed expression of RAG-1 mRNA in spinal cord (but not brain) of control mice; no expression of RAG-1 mRNA was detected in spinal cord or brain from wst/wst mice or their normal littermates (wst/{center_dot} mice). In thymus tissue, a small RAG-1 transcript (1.0 kb) was detected in wst/wst mice that was not evident in thymus from control mice. In wst/{center_dot} mice, a two-fold increase in RAG-1 MRNA was evident in thymus tissue. RAG-2 mRNA could only be detected in thymus tissue from wst/{center_dot} and not from wst/wst or parental control BCF{sub 1} mice. Southern blots revealed a rearrangement/deletion within the RAG-1 gene of affected wasted mice, not evident in known strain-specific parental or littermate controls. These results support the idea that the RAG-1 gene may map at or near the locus for the wasted mutation. In addition, they suggest the importance of recombinase function in normal immune and central nervous system development as well as the potential contribution of this gene family to the normal repair of radiation-induced DNA damage.

  10. Rearrangements of chicken immunoglobulin genes in lymphoid cells transformed by the avian retroviral oncogene v-rel.

    Science.gov (United States)

    Chen, L; Lim, M Y; Bose, H; Bishop, J M

    1988-01-01

    The retroviral oncogene v-rel transforms poorly characterized lymphoid cells. We have explored the nature of these cells by analyzing the configuration and expression of immunoglobulin genes in chicken hemopoietic cells transformed by v-rel. None of the transformed cells expressed their immunoglobulin genes. The cells fell into three classes: class I cells have their immunoglobulin genes potentially in an embryonic configuration; class II and class III cells have lost one copy of the lambda light chain locus and have one copy of the heavy chain locus rearranged into a configuration that differs from what is found in mature B cells. In class II cells, the other heavy chain locus may be in embryonic configuration, whereas it is deleted in class III cells. The first of these classes may represent the earliest stage of the lymphoid lineage yet encountered among virus-transformed cells, whereas the second and third classes represent an apparently anomalous rearrangement whose origin remains unknown.

  11. Detection of immunoglobulin IGH gene rearrangements on formalin-fixed, paraffin embedded tissue in lymphoid malignancies.

    Science.gov (United States)

    Moharrami, G; Ghorbian, S; Seifi, M; Estiar, M A; Fakhrjoo, A; Sakhinia, M; Sakhinia, E

    2014-01-01

    Human lymphomas are aggressive malignant diseases, which can be categorized based on their B and T cell lineage. B-cell lymphomas form around 90% of the total lymphoma cases, the remnants of malignancies arise from the T cell branch. Lymphomas are mostly characterized as clonal proliferations of specific tumor cells. The detection of malignant lymphomas are extensively investigated by their morphological features, immunohistochemistry and flowcytometric immunophenotyping, but in some of cases remained unknown. The BIOMED-2 protocols were used to determine the clonality of IGH gene rearrangements in patients with lymphoma. PCR amplification was performed on FFPE of 50 patients with B-cell lymphoma, which consisted of 11 cases with HLs, 25 cases of B-NHLs and 14 cases of B-LPD (lymphoproliferative disorders) that diagnosed as unclassifiable lymphoma. The rate of positive clonality was detected in 96% (24/25) of B-NHLs, whereas in 4% (1/25) of cases clonality was showed in a polyclonal pattern. In B-HLs, 82% (9/11) of cases showed clonality and 18% (2/11) of the cases showed polyclonality. The rate of positive clonality observed in 64.3% (9/14) of cases with B-LPD and 35.7% (5/14) of cases clonality was not detected in any of immunoglobulin gene family (FR1, FR2, FR3). In groups with DLBCL, clonality was detected in 95% (19/20) of the cases. In patients diagnosed with FL and MALTs 100% cases showed clonality for complete IGH. Our study revealed that EuroClonality BIOMED-2 protocols could be considered as a valuable and reliable method for clonality detection, especially in IGH analysis.

  12. Gene rearrangements and evolution of tRNA pseudogenes in the mitochondrial genome of the parrotfish (Teleostei: Perciformes: Scaridae).

    Science.gov (United States)

    Mabuchi, Kohji; Miya, Masaki; Satoh, Takashi P; Westneat, Mark W; Nishida, Mutsumi

    2004-09-01

    Genomic size of animal mitochondrial DNA is usually minimized over time. Thus, when regional duplications occur, they are followed by a rapid elimination of redundant material. In contrast to this general view, we report here long-sustained tRNA pseudogenes in the mitochondrial genome (mitogenome) of teleost fishes of the family Scaridae (parrotfishes). During the course of a molecular phylogenetic study of the suborder Labroidei, we determined the complete nucleotide sequence of the mitogenome for a parrotfish, Chlorurus sordidus, and found a gene rearrangement accompanied by a tRNA pseudogene. In the typical gene order of vertebrates, a tRNA-gene cluster between ND1 and ND2 genes includes tRNA(Ile) (I), tRNA(Gln) (Q), and tRNA(Met) (M) genes in this order (IQM). However, in the mitogenome of the parrotfish, the tRNA(Met) gene was inserted between the tRNA(Ile) and the tRNA(Gln) genes, and the tRNA(Gln) gene was followed by a putative tRNA(Met) pseudogene (psiM). Such a tRNA gene rearrangement including a pseudogene (IMQpsiM) was found in all of the 10 examined species, representing 7 of the 10 currently recognized scarid genera. All sister groups examined (20 species of Labridae and a single species of Odacidae) had the typical gene order of vertebrate mitogenomes. Phylogenetic analysis of the tRNA(Met) genes and the resulting pseudogenes demonstrated that the ancestral tRNA(Met) gene was duplicated in a common ancestor of the parrotfish. Based on the fossil record, these results indicate that the pseudogenes have survived at least 14 million years. Most of the vertebrate mitochondrial gene rearrangements involving the IQM region have held the tRNA(Met) gene just upstream of the ND2 gene, and even in a few exceptional cases, including the present ones, the tRNA pseudogenes have been found in that position. In addition, most of these tRNA(Met) pseudogenes maintained clover-leaf secondary structures, with the remainder sustaining the clover-leaf structure in the

  13. Systematic characterisation of disease associated balanced chromosome rearrangements by FISH: cytogenetically and genetically anchored YACs identify microdeletions and candidate regions for mental retardation genes

    DEFF Research Database (Denmark)

    Wirth, J; Nothwang, H G; van der Maarel, S;

    1999-01-01

    Disease associated balanced chromosome rearrangements (DBCRs) have been instrumental in the isolation of many disease genes. To facilitate the molecular cytogenetic characterisation of DBCRs, we have generated a set of >1200 non-chimeric, cytogenetically and genetically anchored CEPH YACs...

  14. Assignment of genes encoding metallothioneins I and II to Chinese hamster chromosomes 3. Evidence for the role of chromosome rearrangement in gene amplification

    Energy Technology Data Exchange (ETDEWEB)

    Stallings, R.L.; Munk, A.C.; Longmire, J.L.; Hildebrand, C.E.; Crawford, B.D.

    1984-12-01

    Cadmium resistant (Cd/sup r/) variants with coordinately amplified metallothionein I and II (MTI and MTII) genes have been derived from both Chinese hamster ovary and near-euploid Chinese hamster cell lines. Cytogenetic analyses of Cd/sup r/ variants consistently revealed breakage and rearrangement involving chromosome 3p. In situ hybridization with Chinese hamster MT-encoding cDNA probe localized amplified MT gene sequences near the translocation breakpoint involving chromosome 3p. These observations suggested that both functionally related, isometallothionein loci are linked on Chinese hamster chromosome 3. Southern blot analyses of DNAs isolated from a panel of Chinese hamster x mouse somatic cell hybrids which segregate hamster chromosomes confirmed that both MTI and MTII are located on chromosome 3. The authors speculate that rearrangement of chromosome 3p could be causally involved with the amplification of MT genes in Cd/sup r/ hamster cell lines. 34 references, 3 figures, 1 table.

  15. Gene mutations and genomic rearrangements in the mouse as a result of transposon mobilization from chromosomal concatemers.

    Directory of Open Access Journals (Sweden)

    Aron M Geurts

    2006-09-01

    Full Text Available Previous studies of the Sleeping Beauty (SB transposon system, as an insertional mutagen in the germline of mice, have used reverse genetic approaches. These studies have led to its proposed use for regional saturation mutagenesis by taking a forward-genetic approach. Thus, we used the SB system to mutate a region of mouse Chromosome 11 in a forward-genetic screen for recessive lethal and viable phenotypes. This work represents the first reported use of an insertional mutagen in a phenotype-driven approach. The phenotype-driven approach was successful in both recovering visible and behavioral mutants, including dominant limb and recessive behavioral phenotypes, and allowing for the rapid identification of candidate gene disruptions. In addition, a high frequency of recessive lethal mutations arose as a result of genomic rearrangements near the site of transposition, resulting from transposon mobilization. The results suggest that the SB system could be used in a forward-genetic approach to recover interesting phenotypes, but that local chromosomal rearrangements should be anticipated in conjunction with single-copy, local transposon insertions in chromosomes. Additionally, these mice may serve as a model for chromosome rearrangements caused by transposable elements during the evolution of vertebrate genomes.

  16. Rearranged anaplastic lymphoma kinase (ALK) gene found for the first time in adult-onset papillary thyroid cancer cases among atomic bomb survivors

    Energy Technology Data Exchange (ETDEWEB)

    Hamatani, K.; Mukai, M.; Takahashi, K.; Nakachi, K.; Kusunoki, Y. [Radiobiology/Molecular Epidemiology, Radiation Effects Research Foundation, Hiroshima (Japan); Hayashi, Y. [Geriatric Health Service Facility Hidamari, Hiroshima (Japan)

    2012-07-01

    Full text of the publication follows: Thyroid cancer is one of the malignancies most strongly associated with ionizing radiation in humans. Epidemiology studies of atomic bomb (A-bomb) survivors have indicated that excess relative risk of papillary thyroid cancer per Gy was remarkably high in the survivors. We therefore aim to clarify mechanisms linking A-bomb radiation exposure and development of papillary thyroid cancer. Toward this end, we intend to clarify characteristics of gene alterations occurring in radiation-associated adult-onset papillary thyroid cancer from the Life Span Study cohort of A-bomb survivors. We have thus far found that with increased radiation dose, papillary thyroid cancer cases with chromosomal rearrangements (mainly RET/PTC rearrangements) significantly increased and papillary thyroid cancer cases with point mutations (mainly BRAF-V600E) significantly decreased. Papillary thyroid cancer cases with non-detected gene alterations that carried no mutations in RET, NTRK1, BRAF or RAS genes tended to increase with increased radiation dose. In addition, we found that relative frequency of these papillary thyroid cancer cases significantly decreased with time elapsed since exposure. Through analysis of papillary thyroid cancer cases with non-detected gene alterations, we recently discovered a new type of rearrangement for the first time in papillary thyroid cancer, i.e., rearranged anaplastic lymphoma kinase (ALK) gene, although identification of any partner gene(s) is needed. Specifically, rearrangement of ALK was found in 10 of 19 exposed papillary thyroid cancer cases with non-detected gene alterations but not in any of the six non-exposed papillary thyroid cancer cases. Furthermore, papillary thyroid cancer with ALK rearrangement was frequently found in the cases with high radiation dose or with short time elapsed since A-bomb exposure. These results suggest that chromosomal rearrangement, typically of RET and ALK, may play an important

  17. Clinicopathology, immunophenotype, T cell receptor gene rearrangement, Epstein-Barr virus status and p53 gene mutation of cutaneous extranodal NK/T-cell lymphoma, nasal-type

    Institute of Scientific and Technical Information of China (English)

    WANG Ting-ting; XU Chen; LIU Shan-ling; KAN Bei; RAN Yu-ping; LIU Wei-ping; LI Gan-di

    2013-01-01

    Background Extranodal natural killer/T-cell (NK/T cell) lymphoma,nasal-type,is a rare lymphoma.Skin is the second most common site of involvement after the nasal cavity/nasalpharynx.The aim of this study was to investigate the clinicopathologic features,immunophenotype,T cell receptor (TCR) gene rearrangement,the association with Epstein-Barr virus (EBV) infection and p53 gene mutations of the lymphoma.Methods The clinicopathologic analysis,immunohistochemistry,in situ hybridization for EBER1/2,TCR gene rearrangement by polymerase chain reaction (PCR),mutations of p53 gene analyzed by PCR and sequence analysis were employed in this study.Results In the 19 cases,the tumor primarily involved the dermis and subcutaneous layer.Immunohistochemical staining showed that most of the cases expressed CD45RO,CD56,CD3ε,TIA-1 and GrB.Three cases were positive for CD3 and two cases were positive for CD30.Monoclonal TCRY gene rearrangement was found in 7 of 18 cases.The positive rate of EBER1/2 was 100%.No p53 gene mutation was detected on the exon 4-9 in the 18 cases.Fifteen cases showed Pro (proline)/Arg (arginine) single nucleotide polymorphisms (SNPs) on the exon 4 at codon 72.The expression of p53 protein was 72% (13/18) immunohistochemically.Conclusions Cutaneous NK/T-cell lymphoma is a rare but highly aggressive lymphoma with poor prognosis.No p53 gene mutation was detected on the exon 4-9,and Pro/Arg SNPs on p53 codon 72 were detected in the cutaneous NK/T-cell lymphoma.The overexpression of p53 protein may not be the result of p53 gene mutation.

  18. Detection of clonal B cells in microdissected reactive lymphoproliferations: possible diagnostic pitfalls in PCR analysis of immunoglobulin heavy chain gene rearrangement

    DEFF Research Database (Denmark)

    Zhou, X.G.; Sandvej, K.; Gregersen, Niels;

    1999-01-01

    Aims-To evaluate the specificity of standard and fluorescence based (GENESCAN) polymerase chain reaction (PCR) immunoglobulin heavy chain (IgH) gene rearrangement analysis in complete and microdissected paraffin wax embedded sections from lymphoid proliferations. Methods-PCR IgH gene rearrangement...... showed reproducible bands on gel analysis and satisfied accepted criteria for monoclonality. Use of high resolution gels with GENESCAN analysis improved sensitivity and band definition; however, three samples still appeared to be monoclonal. Conclusions These results confirm that PCR based IgH gene...

  19. Balanced gene losses, duplications and intensive rearrangements led to an unusual regularly sized genome in Arbutus unedo chloroplasts.

    Directory of Open Access Journals (Sweden)

    Fernando Martínez-Alberola

    Full Text Available Completely sequenced plastomes provide a valuable source of information about the duplication, loss, and transfer events of chloroplast genes and phylogenetic data for resolving relationships among major groups of plants. Moreover, they can also be useful for exploiting chloroplast genetic engineering technology. Ericales account for approximately six per cent of eudicot diversity with 11,545 species from which only three complete plastome sequences are currently available. With the aim of increasing the number of ericalean complete plastome sequences, and to open new perspectives in understanding Mediterranean plant adaptations, a genomic study on the basis of the complete chloroplast genome sequencing of Arbutus unedo and an updated phylogenomic analysis of Asteridae was implemented. The chloroplast genome of A. unedo shows extensive rearrangements but a medium size (150,897 nt in comparison to most of angiosperms. A number of remarkable distinct features characterize the plastome of A. unedo: five-fold dismissing of the SSC region in relation to most angiosperms; complete loss or pseudogenization of a number of essential genes; duplication of the ndhH-D operon and its location within the two IRs; presence of large tandem repeats located near highly re-arranged regions and pseudogenes. All these features outline the primary evolutionary split between Ericaceae and other ericalean families. The newly sequenced plastome of A. unedo with the available asterid sequences allowed the resolution of some uncertainties in previous phylogenies of Asteridae.

  20. Detection of MYC gene rearrangements by conventional cytogenetics and fluorescent in situ hybridization in patients with acute lymphoblastic leukemia cases

    Directory of Open Access Journals (Sweden)

    Seda Eren

    2015-03-01

    Full Text Available Objective: The aim of this study is to investigate rearrangements at the region of MYC gene by conventional cytogenetics and interphase FISH methods in patients with acute lymphoblastic leukemia (ALL. Methods: The study was carried out on bone marrow specimens of 25 ALL patients who were referred to our laboratory. Fourteen children and 11 adult ALL cases were examined. Conventional cytogenetic analysis was performed using G banding technique and fluorescence in situ hybridization technique was applied using MYC breakapart probe (Cytocell. Results: Totally, in 2 of 25 cases available metaphases were not obtained. While in 9 of 23 cases were found to have normal karyotype (39.1%, numerical chromosomal abnormalities were detected in 6 cases, structural abnormalities in 4 and both numerical and structural abnormalities were found in 4 cases. In one case (4% t(8;14(q24;q32 was found as a cytogenetic aberration in which MYC gene locus involved.FISH analysis was performed successfully in all cases and MYC rearrangements were found in 3 cases (12% by FISH method. Conclusion: By comparing two techniques, it was observed that FISH method showed more sensitivity, however conventional cytogenetic techniques were also effective to reveal all changes of the chromosomes. Therefore, we concluded that it would be more efficient to useof these two techniques together.J Clin Exp Invest 2015;6 (1: 21-26

  1. Laser-based microdissection of single cells from tissue sections and PCR analysis of rearranged immunoglobulin genes from isolated normal and malignant human B cells.

    Science.gov (United States)

    Küppers, Ralf; Schneider, Markus; Hansmann, Martin-Leo

    2013-01-01

    Normal and malignant B cells carry rearranged immunoglobulin (Ig) variable region genes, which due to their practically limitless diversity represent ideal clonal markers for these cells. We describe here an approach to isolate single cells from frozen tissue sections by microdissection using a laser-based method. From the isolated cells rearranged IgH and Igκ genes are amplified in a semi-nested PCR approach, using a collection of V gene family-specific primers recognizing nearly all V gene segments together with primers for the J gene segments. By sequence analysis of V genes from distinct cells, the clonal relationship of the B lineage cells can unequivocally be determined and related to the histological distribution of the cells. The approach is also useful to determine V, D, and J gene usage. Moreover, the presence and pattern of somatic Ig V gene mutations give valuable insight into the stage of differentiation of the B cells.

  2. Epigenetic and 3-dimensional regulation of V(D)J rearrangement of immunoglobulin genes.

    Science.gov (United States)

    Degner-Leisso, Stephanie C; Feeney, Ann J

    2010-12-01

    V(D)J recombination is a crucial component of the adaptive immune response, allowing for the production of a diverse antigen receptor repertoire (Ig and TCR). This review will focus on how epigenetic regulation and 3-dimensional (3D) interactions may control V(D)J recombination at Ig loci. The interplay between transcription factors and post-translational modifications at the Igh, Igκ, and Igλ loci will be highlighted. Furthermore, we propose that the spatial organization and epigenetic boundaries of each Ig loci before and during V(D)J recombination may be influenced in part by the CTCF/cohesin complex. Taken together, the many epigenetic and 3D layers of control ensure that Ig loci are only rearranged at appropriate stages of B cell development.

  3. Prevalence of Gene Rearrangements in Mexican Children with Acute Lymphoblastic Leukemia: A Population Study—Report from the Mexican Interinstitutional Group for the Identification of the Causes of Childhood Leukemia

    OpenAIRE

    Vilma Carolina Bekker-Méndez; Enrique Miranda-Peralta; Juan Carlos Núñez-Enríquez; Irma Olarte-Carrillo; Francisco Xavier Guerra-Castillo; Ericka Nelly Pompa-Mera; Alicia Ocaña-Mondragón; Angélica Rangel-López; Roberto Bernáldez-Ríos; Aurora Medina-Sanson; Elva Jiménez-Hernández; Raquel Amador-Sánchez; José Gabriel Peñaloza-González; José de Diego Flores-Chapa; Arturo Fajardo-Gutiérrez

    2014-01-01

    Mexico has one of the highest incidences of childhood leukemia worldwide and significantly higher mortality rates for this disease compared with other countries. One possible cause is the high prevalence of gene rearrangements associated with the etiology or with a poor prognosis of childhood acute lymphoblastic leukemia (ALL). The aims of this multicenter study were to determine the prevalence of the four most common gene rearrangements [ETV6-RUNX1, TCF3-PBX1, BCR-ABL1, and MLL rearrangement...

  4. Imperfect conformation of experimental and epidemiological data for frequency of RET/РТС gene rearrangements in papillary thyroid carcinoma for the Chernobyl accident

    Directory of Open Access Journals (Sweden)

    Ushenkova L.N.

    2013-12-01

    Full Text Available In an overview and analytical study of the epidemiological data on the frequency of RET/РТС gene rearrangements in sporadic and radiogenic (patients after radiotherapy, residents of contaminated after the Chernobyl disaster areas, victims after the atomic bombings, etc. carcinomas of the thyroid gland were examined. In general, the observed epidemiological laws were confirmed in radiobiology experiments by irradiation of different cultures of thyroid cells and ex vivo with the exception of Chernobyl cohorts. Induction of RET/РТС gene rearrangements by 131l exposure in children carcinomas of Chernobyl residents in mice did not observe too. It is concluded that the situation with the frequency of RET/РТС rearrangements in thyroid carcinoma in Chernobyl cohorts once again confirms the multifactorial nature of the induction and development of these tumors with a contribution of radiation and non-radiation factors (iodine deficiency and different stresses.

  5. Consistent deregulation of gene expression between human and murine MLL-rearrangement leukemias

    OpenAIRE

    Li, Zejuan; Luo, Roger T.; Mi, Shuangli; Sun, Miao; Ping CHEN; Bao, Jingyue; Neilly, Mary Beth; Jayathilaka, Nimanthi; Johnson, Deborah S.; Wang, Lili; Lavau, Catherine; Zhang, Yanming; Tseng, Charles; Zhang, Xiuqing; Wang, Jian

    2009-01-01

    Important biological and pathological properties are often conserved across species. Although several mouse leukemia models have been well established, the genes deregulated in both human and murine leukemia cells have not been studied systematically. We performed a serial analysis of gene expression (SAGE) analysis on gene expression in both human and murine MLL-ELL or MLL-ENL leukemia cells, and identified 88 genes that appeared to be significantly deregulated in both types of leukemia cell...

  6. Rearrangement and expression of beta-T-cell receptor and immunoglobulin genes in established Ph1 chronic myelogenous leukemia cell lines.

    Science.gov (United States)

    Berenson, J; Koeffler, H P

    1989-01-01

    We have determined the arrangement and expression of immunoglobulin (Ig) and beta-T-cell receptor (TCR) genes in six established Philadelphia chromosome-positive (Ph1) chronic myelogenous leukemia (CML) cell lines, and correlated these results with their phenotypic characteristics. Three cell lines with nonlymphoid characteristics, EM2, EM3, and K562, did not demonstrate rearrangement or expression of Ig or beta-TCR genes. A new cell line, MB, with a mature B-cell phenotype recently established in our laboratory, contained light and heavy chain immunoglobulin gene rearrangements and expressed mature Ig RNA. In a cell line with an early lymphoid phenotype, BV173, this analysis showed rearrangement of Ig heavy chain and beta-TCR genes, unrearranged Ig light chain DNA, and expression of only an immature beta-TCR transcript. This line provides evidence for T-cell lineage involvement in Ph1 CML. One cell line without markers of any cell type, KCL-22, demonstrated rearranged, unexpressed Ig heavy chain genes, suggesting these cells are at the very earliest stages of lymphoid differentiation. These lines should provide valuable tools to dissect the molecular biology of differentiation in CML and in early lymphocytes.

  7. Spontaneous recurrent mutations and a complex rearrangement in the MECP2 gene in the light of current models of mutagenesis.

    Science.gov (United States)

    Todorov, Tihomir; Todorova, Albena; Motoescu, Cristina; Dimova, Petia; Iancu, Daniela; Craiu, Dana; Stoian, Daniela; Barbarii, Ligia; Bojinova, Veneta; Mitev, Vanyo

    2012-06-01

    Mutations in the methyl-CpG-binding protein 2 (MECP2) gene are associated with Rett syndrome (RTT). The MECP2 gene has some unique characteristics: (1) it is mainly affected by de novo mutations, due to recurrent independent mutational events in a defined "hot spot" regions or positions; (2) complex mutational events along a single allele are frequently found in this gene; (3) most mutations arise on paternal X chromosome. The recurrent point mutations involve mainly CpG dinucleotides, where C>T transitions are explained by methylation-mediated deamination. The complex mutational events might be explained by the genomic architecture of the region involving the MECP2 gene. The finding that most spontaneous mutations arise on paternal X-chromosome supports the higher contribution of replication-mediated mechanism of mutagenesis. We present 9 types of mutations in the MECP2 gene, detected in a group of 22 Bulgarian and 6 Romanian classical RTT patients. Thirteen patients were clarified on molecular level (46.4%). The point mutations in our sample account for 61.5%. One intraexonic deletion was detected in the present study (7.7%). One novel insertion c.321_322insGAAG, p.(Lys107_Leu108insGluAlafs2*) was found (7.7%). Large deletions and complex mutations account for 23%. A novel complex mutational event c.[584_624del41insTT; 638delTinsCA] was detected in a Romanian patient. We discuss different types of the MECP2 mutations detected in our sample in the light of the possible mechanisms of mutagenesis. Complex gene rearrangements involving a combination of deletions and insertions have always been most difficult to detect, to specify precisely and hence to explain in terms of their underlying mutational mechanisms.

  8. Comparative investigations of T cell receptor gamma gene rearrangements in frozen and formalin-fixed paraffin wax-embedded tissues by capillary electrophoresis

    DEFF Research Database (Denmark)

    Christensen, M; Funder, A D; Bendix, K;

    2006-01-01

    AIM: To compare clonal T cell receptor gamma (TCRgamma) gene rearrangements in frozen and formalin-fixed paraffin wax-embedded (FFPE) tissue, using capillary electrophoresis for use in diagnostics, as T cell lymphomas may be difficult to diagnose by conventional methods. METHODS: The DNA for PCR...

  9. Comparison of different polymerase chain reaction-based approaches for clonality assessment of immunoglobulin heavy-chain gene rearrangements in B-cell neoplasia

    NARCIS (Netherlands)

    Derksen, P W; Langerak, A W; Kerkhof, E; Wolvers-Tettero, I L; Boor, P P; Mulder, A H; Vrints, L W; Coebergh, J W; van Krieken, J H; Schuuring, E; Kluin, P M; van Dongen, J J

    1999-01-01

    Several frequently applied polymerase chain reaction strategies for analysis of immunoglobulin heavy-chain gene rearrangements were compared by analyzing 70 B-cell lymphoproliferative disorders and 24 reactive lymphoid lesions. Southern blot analysis was used as the "gold standard" for clonality ass

  10. Detection of monoclonal immunoglobulin heavy chain gene rearrangement (FR3 in Thai malignant lymphoma by High Resolution Melting curve analysis

    Directory of Open Access Journals (Sweden)

    Pongpruttipan Tawatchai

    2010-05-01

    Full Text Available Abstract Malignant lymphoma, especially non-Hodgkin lymphoma, is one of the most common hematologic malignancies in Thailand. The diagnosis of malignant lymphoma is often problematic, especially in early stages of the disease. Detection of antigen receptor gene rearrangement including T cell receptor (TCR and immunoglobulin heavy chain (IgH by polymerase chain reaction followed by heteroduplex has currently become standard whereas fluorescent fragment analysis (GeneScan has been used for confirmation test. In this study, three techniques had been compared: thermocycler polymerase chain reaction (PCR followed by heteroduplex and polyacrylamide gel electrophoresis, GeneScan analysis, and real time PCR with High Resolution Melting curve analysis (HRM. The comparison was carried out with DNA extracted from paraffin embedded tissues diagnosed as B- cell non-Hodgkin lymphoma. Specific PCR primers sequences for IgH gene variable region 3, including fluorescence labeled IgH primers were used and results were compared with HRM. In conclusion, the detection IgH gene rearrangement by HRM in the LightCycler System showed potential for distinguishing monoclonality from polyclonality in B-cell non-Hodgkin lymphoma. Introduction Malignant lymphoma, especially non-Hodgkin lymphoma, is one of the most common hematologic malignancies in Thailand. The incidence rate as reported by Ministry of Public Health is 3.1 per 100,000 population in female whereas the rate in male is 4.5 per 100,000 population 1. At Siriraj Hospital, the new cases diagnosed as malignant lymphoma were 214.6 cases/year 2. The diagnosis of malignant lymphoma is often problematic, especially in early stages of the disease. Therefore, detection of antigen receptor gene rearrangement including T cell receptor (TCR and immunoglobulin heavy chain (IgH by polymerase chain reaction (PCR assay has recently become a standard laboratory test for discrimination of reactive from malignant clonal

  11. Generation of antigenic diversity in Plasmodium falciparum by structured rearrangement of Var genes during mitosis.

    Directory of Open Access Journals (Sweden)

    Antoine Claessens

    2014-12-01

    Full Text Available The most polymorphic gene family in P. falciparum is the ∼60 var genes distributed across parasite chromosomes, both in the subtelomeres and in internal regions. They encode hypervariable surface proteins known as P. falciparum erythrocyte membrane protein 1 (PfEMP1 that are critical for pathogenesis and immune evasion in Plasmodium falciparum. How var gene sequence diversity is generated is not currently completely understood. To address this, we constructed large clone trees and performed whole genome sequence analysis to study the generation of novel var gene sequences in asexually replicating parasites. While single nucleotide polymorphisms (SNPs were scattered across the genome, structural variants (deletions, duplications, translocations were focused in and around var genes, with considerable variation in frequency between strains. Analysis of more than 100 recombination events involving var exon 1 revealed that the average nucleotide sequence identity of two recombining exons was only 63% (range: 52.7-72.4% yet the crossovers were error-free and occurred in such a way that the resulting sequence was in frame and domain architecture was preserved. Var exon 1, which encodes the immunologically exposed part of the protein, recombined in up to 0.2% of infected erythrocytes in vitro per life cycle. The high rate of var exon 1 recombination indicates that millions of new antigenic structures could potentially be generated each day in a single infected individual. We propose a model whereby var gene sequence polymorphism is mainly generated during the asexual part of the life cycle.

  12. Prevalence of Gene Rearrangements in Mexican Children with Acute Lymphoblastic Leukemia: A Population Study—Report from the Mexican Interinstitutional Group for the Identification of the Causes of Childhood Leukemia

    Science.gov (United States)

    Bekker-Méndez, Vilma Carolina; Miranda-Peralta, Enrique; Núñez-Enríquez, Juan Carlos; Olarte-Carrillo, Irma; Guerra-Castillo, Francisco Xavier; Pompa-Mera, Ericka Nelly; Ocaña-Mondragón, Alicia; Bernáldez-Ríos, Roberto; Medina-Sanson, Aurora; Jiménez-Hernández, Elva; Amador-Sánchez, Raquel; Peñaloza-González, José Gabriel; de Diego Flores-Chapa, José; Fajardo-Gutiérrez, Arturo; Flores-Lujano, Janet; Rodríguez-Zepeda, María del Carmen; Dorantes-Acosta, Elisa María; Bolea-Murga, Victoria; Núñez-Villegas, Nancy; Velázquez-Aviña, Martha Margarita; Torres-Nava, José Refugio; Reyes-Zepeda, Nancy Carolina; González-Bonilla, Cesar; Mejía-Aranguré, Juan Manuel

    2014-01-01

    Mexico has one of the highest incidences of childhood leukemia worldwide and significantly higher mortality rates for this disease compared with other countries. One possible cause is the high prevalence of gene rearrangements associated with the etiology or with a poor prognosis of childhood acute lymphoblastic leukemia (ALL). The aims of this multicenter study were to determine the prevalence of the four most common gene rearrangements [ETV6-RUNX1, TCF3-PBX1, BCR-ABL1, and MLL rearrangements] and to explore their relationship with mortality rates during the first year of treatment in ALL children from Mexico City. Patients were recruited from eight public hospitals during 2010–2012. A total of 282 bone marrow samples were obtained at each child's diagnosis for screening by conventional and multiplex reverse transcription polymerase chain reaction to determine the gene rearrangements. Gene rearrangements were detected in 50 (17.7%) patients. ETV6-RUNX1 was detected in 21 (7.4%) patients, TCF3-PBX1 in 20 (7.1%) patients, BCR-ABL1 in 5 (1.8%) patients, and MLL rearrangements in 4 (1.4%) patients. The earliest deaths occurred at months 1, 2, and 3 after diagnosis in patients with MLL, ETV6-RUNX1, and BCR-ABL1 gene rearrangements, respectively. Gene rearrangements could be related to the aggressiveness of leukemia observed in Mexican children. PMID:25692130

  13. Prevalence of Gene Rearrangements in Mexican Children with Acute Lymphoblastic Leukemia: A Population Study—Report from the Mexican Interinstitutional Group for the Identification of the Causes of Childhood Leukemia

    Directory of Open Access Journals (Sweden)

    Vilma Carolina Bekker-Méndez

    2014-01-01

    Full Text Available Mexico has one of the highest incidences of childhood leukemia worldwide and significantly higher mortality rates for this disease compared with other countries. One possible cause is the high prevalence of gene rearrangements associated with the etiology or with a poor prognosis of childhood acute lymphoblastic leukemia (ALL. The aims of this multicenter study were to determine the prevalence of the four most common gene rearrangements [ETV6-RUNX1, TCF3-PBX1, BCR-ABL1, and MLL rearrangements] and to explore their relationship with mortality rates during the first year of treatment in ALL children from Mexico City. Patients were recruited from eight public hospitals during 2010–2012. A total of 282 bone marrow samples were obtained at each child’s diagnosis for screening by conventional and multiplex reverse transcription polymerase chain reaction to determine the gene rearrangements. Gene rearrangements were detected in 50 (17.7% patients. ETV6-RUNX1 was detected in 21 (7.4% patients, TCF3-PBX1 in 20 (7.1% patients, BCR-ABL1 in 5 (1.8% patients, and MLL rearrangements in 4 (1.4% patients. The earliest deaths occurred at months 1, 2, and 3 after diagnosis in patients with MLL, ETV6-RUNX1, and BCR-ABL1 gene rearrangements, respectively. Gene rearrangements could be related to the aggressiveness of leukemia observed in Mexican children.

  14. Ewing Sarcoma With ERG Gene Rearrangements: A Molecular Study Focusing on the Prevalence of FUS-ERG and Common Pitfalls in Detecting EWSR1-ERG Fusions by FISH

    Science.gov (United States)

    Chen, Sonja; Deniz, Kemal; Sung, Yun-Shao; Zhang, Lei; Dry, Sarah; Antonescu, Cristina R.

    2016-01-01

    The genetics of Ewing sarcoma (ES) are characterized by a canonical fusion involving EWSR1 gene and a member of the ETS family of transcription factors, such as FLI1 and ERG. In fact, ERG gene rearrangements represent the second most common molecular alteration, with EWSR1-ERG being identified in 5–10% of cases, while only a handful of reports document a FUS-ERG fusion. In this study, we focus on ES with ERG gene abnormalities, specifically to investigate the prevalence and clinicopathologic features of FUS-ERG fusions in a large cohort of small blue round cell tumors (SBRCTs) and compare to the eight reported FUS-positive ES. Among the 85 SBRCTs tested, seven (8.2%) cases harbored FUS gene rearrangements; six fused to ERG and one with FEV. During this investigation we came across a number of ERG-rearranged ES lacking both EWSR1 and FUS abnormalities by FISH. In one case, RNA sequencing identified an EWSR1-ERG transcript despite the negative EWSR1 rearrangements by FISH. Additional 3-color FISH fusion assay demonstrated the fusion of EWSR1 and ERG signals in all four cases negative for break-apart EWSR1 FISH. These results emphasize a potential pitfall of relying on EWSR1 FISH assay alone for diagnosis of ES. In cases with classic morphology and/or strong CD99 and ERG immunoreactivity, additional molecular testing should be applied, such as ERG FISH or RT-PCR/next generation sequencing, for a more definitive diagnosis. Although our study group is small, there were no differences noted between the clinical, morphologic features and immunoprofile of the different subsets of ERG-rearranged SBRCTs. PMID:26690869

  15. Exonic rearrangements in the known Parkinson's disease-causing genes are a rare cause of the disease in South African patients.

    Science.gov (United States)

    van der Merwe, Celia; Carr, Jonathan; Glanzmann, Brigitte; Bardien, Soraya

    2016-04-21

    Parkinson's disease (PD) is a neurodegenerative movement disorder characterized by the loss of dopaminergic neurons in the substantia nigra of the midbrain. To date, a number of PD-causing genes have been found, including SNCA, LRRK2, VPS35, PARK2, PINK1, DJ-1, ATP13A2, and most recently CHCHD2. Mutations in these genes range from point mutations to larger exonic rearrangements including deletions and duplications. This study aimed to detect possible copy number variation (CNV) in the known PD-causing genes in a cohort of South African patients with PD. Multiplex Ligation-dependent Probe Amplification (MLPA) analysis was performed on a total of 210 South African PD patients, and possible CNVs were verified using quantitative real time PCR. No homozygous or compound heterozygous exon rearrangements in the genes analysed were found in the patient group. A heterozygous PARK2 exon 4 deletion was found in a sporadic patient with an age at onset of 51 years. Sanger sequencing did not reveal any additional mutations in PARK2 in this patient. Combining our results with that of previous studies in a South African cohort, the frequency of exonic rearrangements in the known PD-causing genes is only 1.8% (8/439 patients). In conclusion, CNV in the known PD-causing genes are a rare cause of PD in a South African cohort, and there may be as yet unknown genetic causes of PD that are specific to patients of African ethnicity.

  16. Rearrangements of MYC gene facilitate risk stratification in diffuse large B-cell lymphoma patients treated with rituximab-CHOP

    DEFF Research Database (Denmark)

    Tzankov, Alexandar; Xu-Monette, Zijun Y; Gerhard, Marc;

    2014-01-01

    In order to address the debatable prognostic role of MYC rearrangements in diffuse large B-cell lymphoma patients treated with rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone, we evaluated MYC rearrangements by fluorescence in situ hybridization in 563 cases using br...

  17. Mechanisms of chromosomal rearrangement in the human genome

    Directory of Open Access Journals (Sweden)

    Lieber Michael R

    2010-02-01

    Full Text Available Abstract Many human cancers are associated with characteristic chromosomal rearrangements, especially hematopoietic cancers such as leukemias and lymphomas. The first and most critical step in the rearrangement process is the induction of two DNA double-strand breaks (DSB. In all cases, at least one of the two DSBs is generated by a pathologic process, such as (1 randomly-positioned breaks due to ionizing radiation, free radical oxidative damage, or spontaneous hydrolysis; (2 breaks associated with topoisomerase inhibitor treatment; or (3 breaks at direct or inverted repeat sequences, mediated by unidentified strand breakage mechanisms. In lymphoid cells, one of the two requisite DSBs is often physiologic, the result of V(DJ recombination or class switch recombination (CSR at the lymphoid antigen receptor loci. The RAG complex, which causes the DSBs in V(DJ recombination, can cause (4 sequence-specific, pathologic DSBs at sites that fit the consensus of their normal V(DJ recombination signal targets; or (5 structure-specific, pathologic DSBs at regions of single- to double-strand transition. CSR occurs specifically in the B-cell lineage, and requires (6 activation-induced cytidine deaminase (AID action at sites of single-stranded DNA, which may occur pathologically outside of the normal target loci of class switch recombination regions and somatic hypermutation (SHM zones. Recent work proposes a seventh mechanism: the sequential action of AID and the RAG complex at CpG sites provides a coherent model for the pathologic DSBs at some of the most common sites of translocation in human lymphoma – the bcl-2 gene in follicular lymphoma and diffuse large B-cell lymphoma, and the bcl-1 gene in mantle cell lymphoma.

  18. Rearrangement of Upstream Regulatory Elements Leads to Ectopic Expression of the Drosophila Mulleri Adh-2 Gene

    Science.gov (United States)

    Falb, D.; Fischer, J.; Maniatis, T.

    1992-01-01

    The Adh-2 gene of Drosophila mulleri is expressed in the larval fat body and the adult fat body and hindgut, and a 1500-bp element located 2-3 kb upstream of the Adh-2 promoter is necessary for maximal levels of transcription. Previous work demonstrated that deletion of sequences between this upstream element and the Adh-2 promoter results in Adh-2 gene expression in a novel larval tissue, the middle midgut. In this study we show that the upstream element possesses all of the characteristics of a transcriptional enhancer: its activity is independent of orientation, it acts on a heterologous promoter, and it functions at various positions both 5' and 3' to the Adh-2 gene. Full enhancer function can be localized to a 750-bp element, although other regions possess some redundant activity. The ectopic expression pattern is dependent on the proximity of at least two sequence elements. Thus, tissue-specific transcription can involve complex proximity-dependent interactions among combinations of regulatory elements. PMID:1459428

  19. Environmental and chemotherapeutic agents induce breakage at genes involved in leukemia-causing gene rearrangements in human hematopoietic stem/progenitor cells

    Energy Technology Data Exchange (ETDEWEB)

    Thys, Ryan G., E-mail: rthys@wakehealth.edu [Department of Cancer Biology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1016 (United States); Lehman, Christine E., E-mail: clehman@wakehealth.edu [Department of Cancer Biology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1016 (United States); Pierce, Levi C.T., E-mail: Levipierce@gmail.com [Human Longevity, Inc., San Diego, California 92121 (United States); Wang, Yuh-Hwa, E-mail: yw4b@virginia.edu [Department of Biochemistry and Molecular Genetics, University of Virginia, 1340 Jefferson Park Avenue, Charlottesville, VA 22908-0733 (United States)

    2015-09-15

    Highlights: • Environmental/chemotherapeutic agents cause DNA breakage in MLL and CBFB in HSPCs. • Diethylnitrosamine-induced DNA breakage at MLL and CBFB shown for the first time. • Chemical-induced DNA breakage occurs at topoisomerase II cleavage sites. • Chemical-induced DNA breaks display a pattern similar to those in leukemia patients. • Long-term exposures suggested to generate DNA breakage at leukemia-related genes. - Abstract: Hematopoietic stem and progenitor cells (HSPCs) give rise to all of the cells that make up the hematopoietic system in the human body, making their stability and resilience especially important. Damage to these cells can severely impact cell development and has the potential to cause diseases, such as leukemia. Leukemia-causing chromosomal rearrangements have largely been studied in the context of radiation exposure and are formed by a multi-step process, including an initial DNA breakage and fusion of the free DNA ends. However, the mechanism for DNA breakage in patients without previous radiation exposure is unclear. Here, we investigate the role of non-cytotoxic levels of environmental factors, benzene, and diethylnitrosamine (DEN), and chemotherapeutic agents, etoposide, and doxorubicin, in generating DNA breakage at the patient breakpoint hotspots of the MLL and CBFB genes in human HSPCs. These conditions represent exposure to chemicals encountered daily or residual doses from chemotherapeutic drugs. Exposure of HSPCs to non-cytotoxic levels of environmental chemicals or chemotherapeutic agents causes DNA breakage at preferential sites in the human genome, including the leukemia-related genes MLL and CBFB. Though benzene, etoposide, and doxorubicin have previously been linked to leukemia formation, this is the first study to demonstrate a role for DEN in the generation of DNA breakage at leukemia-specific sites. These chemical-induced DNA breakpoints coincide with sites of predicted topoisomerase II cleavage. The

  20. Environmental and chemotherapeutic agents induce breakage at genes involved in leukemia-causing gene rearrangements in human hematopoietic stem/progenitor cells

    International Nuclear Information System (INIS)

    Highlights: • Environmental/chemotherapeutic agents cause DNA breakage in MLL and CBFB in HSPCs. • Diethylnitrosamine-induced DNA breakage at MLL and CBFB shown for the first time. • Chemical-induced DNA breakage occurs at topoisomerase II cleavage sites. • Chemical-induced DNA breaks display a pattern similar to those in leukemia patients. • Long-term exposures suggested to generate DNA breakage at leukemia-related genes. - Abstract: Hematopoietic stem and progenitor cells (HSPCs) give rise to all of the cells that make up the hematopoietic system in the human body, making their stability and resilience especially important. Damage to these cells can severely impact cell development and has the potential to cause diseases, such as leukemia. Leukemia-causing chromosomal rearrangements have largely been studied in the context of radiation exposure and are formed by a multi-step process, including an initial DNA breakage and fusion of the free DNA ends. However, the mechanism for DNA breakage in patients without previous radiation exposure is unclear. Here, we investigate the role of non-cytotoxic levels of environmental factors, benzene, and diethylnitrosamine (DEN), and chemotherapeutic agents, etoposide, and doxorubicin, in generating DNA breakage at the patient breakpoint hotspots of the MLL and CBFB genes in human HSPCs. These conditions represent exposure to chemicals encountered daily or residual doses from chemotherapeutic drugs. Exposure of HSPCs to non-cytotoxic levels of environmental chemicals or chemotherapeutic agents causes DNA breakage at preferential sites in the human genome, including the leukemia-related genes MLL and CBFB. Though benzene, etoposide, and doxorubicin have previously been linked to leukemia formation, this is the first study to demonstrate a role for DEN in the generation of DNA breakage at leukemia-specific sites. These chemical-induced DNA breakpoints coincide with sites of predicted topoisomerase II cleavage. The

  1. Characterization of novel non-clonal intrachromosomal rearrangements between the H4 and PTEN genes (H4/PTEN) in human thyroid cell lines and papillary thyroid cancer specimens

    Energy Technology Data Exchange (ETDEWEB)

    Puxeddu, Efisio [Division of Endocrinology and Metabolism, University of Cincinnati College of Medicine, PO Box 670547, Cincinnati, OH 45267-0547 (United States); Zhao Guisheng [Division of Endocrinology and Metabolism, University of Cincinnati College of Medicine, PO Box 670547, Cincinnati, OH 45267-0547 (United States); Stringer, James R. [Department of Molecular Genetics, University of Cincinnati College of Medicine, PO Box 670547, Cincinnati, OH 45267-0547 (United States); Medvedovic, Mario [Center for Biostatistic Service, University of Cincinnati College of Medicine, PO Box 670547, Cincinnati, OH 45267-0547 (United States); Moretti, Sonia [Dipartimento di Medicina Interna, Universita degli Studi di Perugia, Via E. dal Pozzo, Perugia 06126, (Italy); Fagin, James A. [Division of Endocrinology and Metabolism, University of Cincinnati College of Medicine, PO Box 670547, Cincinnati, OH 45267-0547 (United States)]. E-mail: james.fagin@uc.edu

    2005-02-15

    The two main forms of RET rearrangement in papillary thyroid carcinomas (PTC) arise from intrachromosomal inversions fusing the tyrosine kinase domain of RET with either the H4 (RET/PTC1) or the ELE1/RFG genes (RET/PTC3). PTEN codes for a dual-specificity phosphatase and maps to chromosome 10q22-23. Germline mutations confer susceptibility to Cowden syndrome whereas somatic mutations or deletions are common in several sporadic human tumors. Decreased PTEN expression has been implicated in thyroid cancer development. We report the characterization of a new chromosome 10 rearrangement involving H4 and PTEN. The initial H4/PTEN rearrangement was discovered as a non-specific product of RT-PCR for RET/PTC1 in irradiated thyroid cell lines. Sequencing revealed a transcript consisting of exon 1 and 2 of H4 fused with exons 3-6 of PTEN. Nested RT-PCR with specific primers bracketing the breakpoints confirmed the H4/PTEN rearrangements in irradiated KAT-1 and KAT-50 cells. Additional H4/PTEN variants, generated by recombination of either exon 1 or exon 2 of H4 with exon 6 of PTEN, were found in non-irradiated KAK-1, KAT-50, ARO and NPA cells. Their origin through chromosomal recombination was confirmed by detection of the reciprocal PTEN/H4 product. H4/PTEN recombination was not a clonal event in any of the cell lines, as Southern blots with appropriate probes failed to demonstrate aberrant bands, and multicolor FISH of KAK1 cells with BAC probes for H4 and PTEN did not show a signal overlap in all cells. Based on PCR of serially diluted samples, the minimal frequency of spontaneous recombination between these loci was estimated to be approximately 1/10{sup 6} cells. H4/PTEN products were found by nested RT-PCR in 4/14 normal thyroid tissues (28%) and 14/18 PTC (78%) (P < 0.01). H4/PTEN is another example of recombination involving the H4 locus, and points to the high susceptibility of thyroid cells to intrachromosomal gene rearrangements. As this also represents a

  2. Clinicopathological study of gene rearrangement and immunohistochemical pattern of primary intracranial diffuse large B-cell lymphomas

    Directory of Open Access Journals (Sweden)

    Han X

    2013-11-01

    Full Text Available We studied the clinicopathological and imaging characteristics of primary intracranial diffuse large B-cell lymphomas (PIC-DLBCL. Imaging, histopathological findings, and immunohistochemical staining characteristics were analyzed, and the immunoglobulin heavy and light chain gene rearrangement of 25 PIC-DLBCL cases was examined. MicroRNA was extracted from 10 cases each of PIC-DLBCL, extracerebral germinal center DLBCL (GC-DLBCL, and extracerebral non-GC-DLBCL (NGC-DLBCL; we conducted chip hybridization and comparatively analyzed the difference among the three. PIC-DLBCLs typically involved no less than two cerebral lobes (10/25; the frontal lobe was affected most often (6/25. Target-shaped structures were observed in all PIC-DLBCLs due to the proliferation of centroblast-like large lymphocytes surrounding the vessels. There was strong and diffuse immunostaining for CD20 and CD79a, and negative immunostaining for CD3, CD5, CD23, and cyclin D1 for all PIC-DLBCLs. The percentage of cells with nuclear positivity for anti-Ki67 antibody ranged 50-90% (mean, 80%. Three, 19, and 22 PIC-DLBCLs were CD10-, Bcl-6-, and melanoma ubiquitous mutated 1-positive, respectively. Twenty-four PIC-DLBCLs were B-cell monoclonal. MicroRNA hybridization showed that 788 PIC-DLBCL microRNAs/segments increased to at least twice of that of NGC-DLBCLs, and 401 PIC-DLBCL microRNAs/segments declined to less than half of that of NGC-DLBCLs. Six hundred and eleven PIC-DLBCL microRNAs/segments increased to at least twice that of GC-DLBCLs, and 229 PIC-DLBCL microRNAs/segments declined to less than half of that in GC-DLBCLs. PIC-DLBCL typically affected multiple sites, tended to occur in older men, arose from activated B cells, had high B-cell monoclonality; its microRNA expression differed from that of NGC-DLBCL and GC-DLBCL.

  3. Sequencing and characterisation of rearrangements in three S. pastorianus strains reveals the presence of chimeric genes and gives evidence of breakpoint reuse.

    Directory of Open Access Journals (Sweden)

    Sarah K Hewitt

    Full Text Available Gross chromosomal rearrangements have the potential to be evolutionarily advantageous to an adapting organism. The generation of a hybrid species increases opportunity for recombination by bringing together two homologous genomes. We sought to define the location of genomic rearrangements in three strains of Saccharomyces pastorianus, a natural lager-brewing yeast hybrid of Saccharomyces cerevisiae and Saccharomyces eubayanus, using whole genome shotgun sequencing. Each strain of S. pastorianus has lost species-specific portions of its genome and has undergone extensive recombination, producing chimeric chromosomes. We predicted 30 breakpoints that we confirmed at the single nucleotide level by designing species-specific primers that flank each breakpoint, and then sequencing the PCR product. These rearrangements are the result of recombination between areas of homology between the two subgenomes, rather than repetitive elements such as transposons or tRNAs. Interestingly, 28/30 S. cerevisiae-S. eubayanus recombination breakpoints are located within genic regions, generating chimeric genes. Furthermore we show evidence for the reuse of two breakpoints, located in HSP82 and KEM1, in strains of proposed independent origin.

  4. Destaining of Diff-Quik stained cytologic smears is not necessary for the detection of anaplastic lymphoma kinase gene rearrangement in lung adenocarcinoma by fluorescence in situ hybridization

    Directory of Open Access Journals (Sweden)

    Weisheng Xu

    2016-01-01

    Full Text Available Background: Anaplastic lymphoma kinase (ALK gene rearrangement analysis by fluorescence in situ hybridization (FISH is one of the standard molecular tests for targeted therapy of lung adenocarcinoma. However, insufficient cell block cellularity may impede molecular testing. A recent study showed that Diff-Quik (DQ stained cytology smear is suitable for ALK by FISH. Aims: The aim of our study was to observe the impact of destaining intervals on the quality of FISH signals and determine if DQ smears without destaining would allow FISH analysis. Materials and Methods: Thirty-five DQ smears from 27 cases of lung adenocarcinoma were analyzed for ALK gene rearrangement by FISH. Twenty three DQ smears were destained for different intervals, including 30 s (13 cases, 1 min (6 cases, or 2 min (4 cases. Twelve DQ smears were not subjected to destaining. For further validation, FISH signals in 8 smears and 6 cell blocks were compared with the paired destained DQ smears. The signal quality was semi-quantified and analyzed with Chi-squared test. Results: Of the total 27 selected cases, three (11% were positive for ALK gene rearrangement, whereas 24 (89% were negative. FISH signal was satisfactory in all DQ smears. There was no significant difference in the quality of signal among smears with different destaining intervals (P = 0.55 or between smears with and without destaining (P = 0.41. DQ smears without destaining showed identical FISH results and similar or better signals as compared with paired destained smears and cell blocks in all cases. Conclusions: Duration of destaining intervals does not impact the quality of FISH signal on DQ smears. Destaining of DQ smears is not necessary for ALK by FISH.

  5. Rapid analysis of rearranged kappa light chain genes of circulating polysaccharide-specific B lymphocytes by means of immunomagnetic beads and the polymerase chain reaction

    DEFF Research Database (Denmark)

    Hougs, L; Barington, T; Madsen, HO;

    1993-01-01

    CP-specific B lymphocytes were isolated by antigen-coated immunomagnetic beads. After the purification, at least 98% of the immunoglobulin-secreting recovered cells were HibCP specific. The RNA was isolated and amplified by cDNA synthesis using a kappa constant region primer followed by polymerase chain...... reaction (PCR) using in addition a degenerate kappa light chain signal peptide region primer. The PCR product was cloned into the M13mp18 phage. The cloning efficiency was 100-600 clones/ml of blood. Of the 86 clones sequenced, 90% represented rearranged kappa light chain genes from different antibody...

  6. Rearreglos de genes de cadenas pesadas de las inmunoglobulinas en las gammapatías monoclonales Immunoglobulin heavy chain gene rearrangements in the monoclonal gammopathies

    Directory of Open Access Journals (Sweden)

    Andrea Bosaleh

    2005-06-01

    gammopathies of unknown significance (MGUS. MGUS present a monoclonal component with no signs of multiple myeloma, Waldenström macroglobulinemia, primary amyloidosis or other disorders. Pathological, radiological and clinical features are required for the diagnosis. Approximately 25% of patients with MGUS will become multiple myeloma, primary amiloidosis, macroglobulinemia, or other lymphoproliferative disease, which would be a premyelomatous condition. The objective of this study was to determine the clinical implications of immunophenotyping by flow cytometry and of the detection of clonality by molecular biology. A total of 32 patients were studied. Seven of them were diagnosed with multiple myeloma, and 25 with monoclonal gammopathy under study. These 32 patients were divided into four groups, based on their clinical data and flow cytometry outcome. In patients with non-diagnostic flow cytometry detection of immunoglobulin heavy chain gene rearrangements by PCR was performed, and monoclonality was found in 59% of the cases. The study of immunoglobulin heavy chain gene rearrangements by molecular biology allows a more sensitive detection of clonality.

  7. A rearrangement of the Z chromosome topology influences the sex-linked gene display in the European corn borer, Ostrinia nubilalis.

    Science.gov (United States)

    Kroemer, Jeremy A; Coates, Brad S; Nusawardani, Tyasning; Rider, S Dean; Fraser, Lisa M; Hellmich, Richard L

    2011-07-01

    Males are homogametic (ZZ) and females are heterogametic (WZ) with respect to the sex chromosomes in many species of butterflies and moths (insect order Lepidoptera). Genes on the Z chromosome influence traits involved in larval development, environmental adaptation, and reproductive isolation. To facilitate the investigation of these traits across Lepidoptera, we developed 43 degenerate primer pairs to PCR amplify orthologs of 43 Bombyx mori Z chromosome-linked genes. Of the 34 orthologs that amplified by PCR in Ostrinia nubilalis, 6 co-segregated with the Z chromosome anchor markers kettin (ket) and lactate dehydrogenase (ldh), and produced a consensus genetic linkage map of ~89 cM in combination with 5 AFLP markers. The O. nubilalis and B. mori Z chromosomes are comparatively co-linear, although potential gene inversions alter terminal gene orders and a translocation event disrupted synteny at one chromosome end. Compared to B. mori orthologs, O. nubilalis Z chromosome-linked genes showed conservation of tissue-specific and growth-stage-specific expression, although some genes exhibited species-specific expression across developmental stages or tissues. The O. nubilalis Z chromosome linkage map provides new tools for isolating quantitative trait loci (QTL) involved in sex-linked traits that drive speciation and it exposes genome rearrangements as a possible mechanism for differential gene regulation in Lepidoptera.

  8. : a database of ciliate genome rearrangements.

    Science.gov (United States)

    Burns, Jonathan; Kukushkin, Denys; Lindblad, Kelsi; Chen, Xiao; Jonoska, Nataša; Landweber, Laura F

    2016-01-01

    Ciliated protists exhibit nuclear dimorphism through the presence of somatic macronuclei (MAC) and germline micronuclei (MIC). In some ciliates, DNA from precursor segments in the MIC genome rearranges to form transcriptionally active genes in the mature MAC genome, making these ciliates model organisms to study the process of somatic genome rearrangement. Similar broad scale, somatic rearrangement events occur in many eukaryotic cells and tumors. The (http://oxytricha.princeton.edu/mds_ies_db) is a database of genome recombination and rearrangement annotations, and it provides tools for visualization and comparative analysis of precursor and product genomes. The database currently contains annotations for two completely sequenced ciliate genomes: Oxytricha trifallax and Tetrahymena thermophila.

  9. Interaction of interleukin-5 with its receptors on murine leukemic BCL1 cells and its implication in biological activity

    International Nuclear Information System (INIS)

    Interaction of interleukin (IL)-5 with its receptors on murine leukemic cell line, BCL1 cells was examined. 125I-labeled recombinant murine IL-5(rmIL-5) bound specifically to high-affinity receptors on BCL1 cells. rmIL-5, which was about 2500-fold more active than recombinant human IL-5(rhIL-5) in IgM-inducing activity on BCL1 cells, also showed about 5000-fold higher affinity to receptors. These results suggest that the bioactivity of IL-5 correlates with its receptor-binding activity. When disulfide bond formation was blocked, rmIL-5 dissociated into a monomer and lost its biological activity. This monomeric form of rmIL-5 also lost its ability to bind to cells, suggesting that dimer formation is essential for the biological activity of IL-5

  10. Characteristic analysis of ETS gene rearrangement in prostate cancer%ETS基因重排在前列腺癌中的特征分析

    Institute of Scientific and Technical Information of China (English)

    戚美; 杨晓庆; 王林; 张娟; 王妍; 韩博

    2013-01-01

    目的 确定前列腺癌人群中ETS家族常见成员基因ERG、ETV1、ETV4和ETV5重排的发生频度;分析ERG基因重排与常见临床及分子病理学指标的关联;验证ERG过表达是否促进前列腺癌细胞上皮间质转化(EMT).方法 荧光原位杂交技术(FISH)检测128例前列腺癌患者肿瘤组织中ERG、ETV1、ETV4和ETV5基因的重排和PTEN基因的缺失;免疫组织化学PV-9000二步法检测前列腺癌组织中雄激素受体(AR)及转录因子SOX4的表达;采用siRNA、Real-time PCR和Western blot检测ERG与前列腺癌细胞EMT的关联.结果 ERG在前列腺癌人群中重排发生率为23% (25/108),其中60%(15/25)的ERG重排患者伴有ERG 5’端的缺失.ETV1、ETV4和ETV5的重排发生率分别为2% (2/109)、1%(1/103)和0%.ERG基因重排与肿瘤远处转移呈正相关(P<0.05),但与Gleason评分、术前PSA水平及肿瘤临床分期等无关联.ERG基因重排与PTEN基因的缺失、SOX4蛋白的表达均呈正相关(P<0.05),但与AR的表达未见相关性;体外实验显示,干扰ERG的表达可抑制前列腺癌Vcap细胞EMT的发生.结论 ERG基因重排在我国前列腺癌患者中的发生频率较西方国家低.ERG基因重排与EMT相关,并可能与其他基因协同发挥促癌作用.%Objective To determine the frequency of ETS (ERG,ETV1,ETV4 and ETV5) gene rearrangement,analyze the relationship between ERG rearrangement and prove whether ERG overexpression can promote the epitheial-mesenchymal transition (EMT) process.Methods Fluorescence in situ hybridization (FISH) was performed to validate the ETS gene aberrations and PTEN deletions of 128 PCa patients.Expression of androgen receptor (AR) and SOX4 was evaluated by using PV-9000 two-step immunohistochemistry method.SiRNA、Real-time PCR and western blot were utilized to study the link between ERG aberration and EMT in PCa in vitro.Results Overall,ERG rearrangement was present in 23% (25/108) cases,of which 60% (15

  11. Genomic and Functional Overlap between Somatic and Germline Chromosomal Rearrangements

    Directory of Open Access Journals (Sweden)

    Sebastiaan van Heesch

    2014-12-01

    Full Text Available Genomic rearrangements are a common cause of human congenital abnormalities. However, their origin and consequences are poorly understood. We performed molecular analysis of two patients with congenital disease who carried de novo genomic rearrangements. We found that the rearrangements in both patients hit genes that are recurrently rearranged in cancer (ETV1, FOXP1, and microRNA cluster C19MC and drive formation of fusion genes similar to those described in cancer. Subsequent analysis of a large set of 552 de novo germline genomic rearrangements underlying congenital disorders revealed enrichment for genes rearranged in cancer and overlap with somatic cancer breakpoints. Breakpoints of common (inherited germline structural variations also overlap with cancer breakpoints but are depleted for cancer genes. We propose that the same genomic positions are prone to genomic rearrangements in germline and soma but that timing and context of breakage determines whether developmental defects or cancer are promoted.

  12. A balanced t(5;17 (p15;q22-23 in chondroblastoma: frequency of the re-arrangement and analysis of the candidate genes

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    Wijers-Koster Pauline

    2009-11-01

    Full Text Available Abstract Background Chondroblastoma is a benign cartilaginous tumour of bone that predominantly affects the epiphysis of long bones in young males. No recurrent chromosomal re-arrangements have so far been observed. Methods: We identified an index case with a balanced translocation by Combined Binary Ratio-Fluorescent in situ Hybridisation (COBRA-FISH karyotyping followed by breakpoint FISH mapping and array-Comparative Genomic Hybridisation (aCGH. Candidate region re-arrangement and candidate gene expression were subsequently investigated by interphase FISH and immunohistochemistry in another 14 cases. Results A balanced t(5;17(p15;q22-23 was identified. In the index case, interphase FISH showed that the translocation was present only in mononucleated cells and was absent in the characteristic multinucleated giant cells. The t(5;17 translocation was not observed in the other cases studied. The breakpoint in 5p15 occurred close to the steroid reductase 5α1 (SRD5A1 gene. Expression of the protein was found in all cases tested. Similar expression was found for the sex steroid signalling-related molecules oestrogen receptor alpha and aromatase, while androgen receptors were only found in isolated cells in a few cases. The breakpoint in 17q22-23 was upstream of the carbonic anhydrase × (CA10 gene region and possibly involved gene-regulatory elements, which was indicated by the lack of CA10 protein expression in the index case. All other cases showed variable levels of CA10 expression, with low expression in three cases. Conclusion We report a novel t(5;17(p15;q22-23 translocation in chondroblastoma without involvement of any of the two chromosomal regions in other cases studied. Our results indicate that the characteristic multinucleated giant cells in chondroblastoma do not have the same clonal origin as the mononuclear population, as they do not harbour the same translocation. We therefore hypothesise that they might be either reactive or

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

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    Anna L Shen

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

  14. Bladder paraganglioma with renal agenesis: A possible new association and its implications in the light of REarranged in transfection gene genetics

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    Rohan Satish Valsangkar

    2015-01-01

    Full Text Available Pheochromocytoma/paraganglioma and renal agenesis are commonly reported conditions. Their coexistence, however, is rare, with few cases reported. We report the case of a 21-year-old male who presented with painless hematuria. He was found to have congenital absent right kidney along with bladder mass on imaging. Examination including blood pressure was normal. He underwent cystoscopy that showed a solid looking tumor on the anterior wall. Paraganglioma was suspected due to intraoperative rise in blood pressure during resection and was confirmed on histopathology. Subsequently after work up and preoperative alpha blockade, patient underwent partial cystectomy and excision of the paravesical mass. Histopathology showed paraganglioma confined to bladder wall with surgical margins free and a paravesical mass that was seminal vesicle cyst. On follow-up, patient is normotensive and asymptomatic. This coexistence of paraganglioma and renal agenesis may have a common genetic mechanism in the form of REarranged in Transfection (RET gene mutation. This is a well-characterized gene, mutations of which are known to be associated with both conditions. Current knowledge of the role of RET gene in both conditions is reviewed to put forth RET mutation as the possible common underlying genetic mechanism along with possible clinical implications of the combination.

  15. Evaluation of multiplex ligation-dependent probe amplification analysis versus multiplex polymerase chain reaction assays in the detection of dystrophin gene rearrangements in an Iranian population subset

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    Nayereh Nouri

    2014-01-01

    Full Text Available Background: The Duchenne muscular dystrophy (DMD gene is located in the short arm of the X chromosome (Xp21. It spans 2.4 Mb of the human genomic DNA and is composed of 79 exons. Mutations in the Dystrophin gene result in DMD and Becker muscular dystrophy. In this study, the efficiency of multiplex ligation-dependent probe amplification (MLPA over multiplex polymerase chain reaction (PCR assays in an Iranian population was investigated. Materials and Methods: Multiplex PCR assays and MLPA analysis were carried out in 74 patients affected with DMD. Results: Multiplex PCR detected deletions in 51% of the patients with DMD. MLPA analysis could determine all the deletions detected by the multiplex PCR. Additionally, MLPA was able to identify one more deletion and duplication in patients without detectable mutations by multiplex PCR. Moreover, MLPA precisely determined the exact size of the deletions. Conclusion: Although MLPA analysis is more sensitive for detection of deletions and duplications in the dystrophin gene, multiplex PCR might be used for the initial analysis of the boys affected with DMD in the Iranian population as it was able to detect 95% of the rearrangements in patients with DMD.

  16. N-terminal truncated human RAG1 proteins can direct T-cell receptor but not immunoglobulin gene rearrangements

    NARCIS (Netherlands)

    J.G. Noordzij; N.S. Verkaik (Nicole); N.G. Hartwig (Nico); R. de Groot (Ronald); D.C. van Gent (Dik); J.J.M. van Dongen (Jacques)

    2000-01-01

    textabstractThe proteins encoded by RAG1 and RAG2 can initiate gene recombination by site-specific cleavage of DNA in immunoglobulin and T-cell receptor (TCR) loci. We identified a new homozygous RAG1 gene mutation (631delT) that leads to a premature stop codon in the 5

  17. The complete mitochondrial genome of Pseudocellus pearsei (Chelicerata: Ricinulei and a comparison of mitochondrial gene rearrangements in Arachnida

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    Braband Anke

    2007-10-01

    Full Text Available Abstract Background Mitochondrial genomes are widely utilized for phylogenetic and population genetic analyses among animals. In addition to sequence data the mitochondrial gene order and RNA secondary structure data are used in phylogenetic analyses. Arachnid phylogeny is still highly debated and there is a lack of sufficient sequence data for many taxa. Ricinulei (hooded tickspiders are a morphologically distinct clade of arachnids with uncertain phylogenetic affinities. Results The first complete mitochondrial DNA genome of a member of the Ricinulei, Pseudocellus pearsei (Arachnida: Ricinulei was sequenced using a PCR-based approach. The mitochondrial genome is a typical circular duplex DNA molecule with a size of 15,099 bp, showing the complete set of genes usually present in bilaterian mitochondrial genomes. Five tRNA genes (trnW, trnY, trnN, trnL(CUN, trnV show different relative positions compared to other Chelicerata (e.g. Limulus polyphemus, Ixodes spp.. We propose that two events led to this derived gene order: (1 a tandem duplication followed by random deletion and (2 an independent translocation of trnN. Most of the inferred tRNA secondary structures show the common cloverleaf pattern except tRNA-Glu where the TψC-arm is missing. In phylogenetic analyses (maximum likelihood, maximum parsimony, Bayesian inference using concatenated amino acid and nucleotide sequences of protein-coding genes the basal relationships of arachnid orders remain unresolved. Conclusion Phylogenetic analyses (ML, MP, BI of arachnid mitochondrial genomes fail to resolve interordinal relationships of Arachnida and remain in a preliminary stage because there is still a lack of mitogenomic data from important taxa such as Opiliones and Pseudoscorpiones. Gene order varies considerably within Arachnida – only eight out of 23 species have retained the putative arthropod ground pattern. Some gene order changes are valuable characters in phylogenetic analysis of

  18. SMAD5 Gene Expression, Rearrangements, Copy Number, Amplification at Fragile Site FRA5C in Human Hepatocellular Carcinoma

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    Drazen B. Zimonjic

    2003-09-01

    Full Text Available Signaling by the transforming growth factor (TGFfamily members is transduced from the cell surface to the nucleus by the Smad group of intracellular proteins. Because we detected alterations on the long arm of chromosome 5, we examined the status of the SMAD5 gene in human hepatocellular carcinoma (HCC cell lines and primary HCC. In 16 cell lines, chromosome alterations of chromosome 5 were observed in nine cell lines by fluorescence in situ hybridization (FISH, an increase in SMAD5 gene copy number relative to the ploidy level was found in eight lines. The breakpoints in unbalanced translocations and deletions frequently occurred near the SMAD5 locus, but apparently did not cause loss of SMAD5. In one cell line, where comparative genomic hybridization showed DNA copy number gain confined to the region 5831, we detected by FISH high-level amplification of the SMAD5 gene located within the fragile site FRA5C. Semiquantitative polymerase chain reaction did not reveal changes in SMAD5 DNA levels in 15 of 17 primary HCC specimens. In 17 HCC cell lines, SMAD5 mRNA levels were either maintained or upregulated by an increase in gene dosage or another mechanism. Collectively, our results show that SMAD5 undergoes copy number gain and increased expression, rather than loss of expression, therefore suggest that this gene does not act as a tumorsuppressor gene in HCC. The Hep-40 HCC cell line with high-level amplification and significant overexpression of SMAD5 may be useful in studying the interaction of SMAD5 with other genes.

  19. The translocation t(2;11)(p21;q23) without MLL gene rearrangement--a possible marker of good prognosis in myelodysplastic syndrome patients.

    Science.gov (United States)

    Dvorak, Pavel; Lysak, Daniel; Vokurka, Samuel; Michalova, Kyra; Sarova, Iveta; Jonasova, Anna; Hruba, Martina; Rykovska, Anna; Subrt, Ivan

    2014-06-01

    The translocation t(2;11)(p21;q23) is associated with de novo myelodysplastic syndromes (MDS) and has an overall frequency of approximately 1%. The outcome of MDS patients with this translocation is not clear until now, because most of the clinical data addressing the t(2;11)(p21;q23) has been collected without investigating the status of the mixed lineage leukemia (MLL) gene. In this report, we present seven new patients with MDS diagnosis and the t(2;11)(p21;q23) in bone marrow cells; all of them without MLL gene rearrangement. They were found in two databases consisting of 1185 patients of two Czech institutions. These patients tended to be younger and showed a strong male predominance. A cytological and histological assessment of bone marrow at diagnosis revealed only mild MDS with marked dysplasia in megakaryopoiesis. Similar to other primary abnormalities in MDS (e.g. deletion of 11q), the t(2;11)(p21;q23) was frequently associated with deletion of 5q. Our results stress the common clinicopathological features of this entity and indicate that the t(2;11)(p21;q23) may be associated with a good prognosis for MDS patients (median survival 72 months).

  20. Wide allelic heterogeneity with predominance of large IDS gene complex rearrangements in a sample of Mexican patients with Hunter syndrome.

    Science.gov (United States)

    Alcántara-Ortigoza, M A; García-de Teresa, B; González-Del Angel, A; Berumen, J; Guardado-Estrada, M; Fernández-Hernández, L; Navarrete-Martínez, J I; Maza-Morales, M; Rius-Domínguez, R

    2016-05-01

    Hunter syndrome or mucopolysaccharidosis type II (MPSII) is caused by pathogenic variants in the IDS gene. This is the first study that examines the mutational spectrum in 25 unrelated Mexican MPSII families. The responsible genotype was identified in 96% of the families (24/25) with 10 novel pathogenic variants: c.133G>C, c.1003C>T, c.1025A>C, c.463_464delinsCCGTATAGCTGG, c.754_767del, c.1132_1133del, c.1463del, c.508-1G>C, c.1006+1G>T and c.(-217_103del). Extensive IDS gene deletions were identified in four patients; using DNA microarray analysis two patients showed the loss of the entire AFF2 gene, and epilepsy developed in only one of them. Wide allelic heterogeneity was noted, with large gene alterations (e.g. IDS/IDSP1 gene inversions, partial to extensive IDS deletions, and one chimeric IDS-IDSP1 allele) that occurred at higher frequencies than previously reported (36% vs 18.9-29%). The frequency of carrier mothers (80%) is consistent with previous descriptions (>70%). Carrier assignment allowed molecular prenatal diagnoses. Notably, somatic and germline mosaicism was identified in one family, and two patients presented thrombocytopenic purpura and pancytopenia after idursulfase enzyme replacement treatment. Our findings suggest a wide allelic heterogeneity in Mexican MPSII patients; DNA microarray analysis contributes to further delineation of the resulting phenotype for IDS and neighboring loci deletions. PMID:26762690

  1. Development of a reverse genetics system for epizootic hemorrhagic disease virus and evaluation of novel strains containing duplicative gene rearrangements.

    Science.gov (United States)

    Yang, Tao; Zhang, Jikai; Xu, Qingyuan; Sun, Encheng; Li, Junping; Lv, Shuang; Feng, Yufei; Zhang, Qin; Wang, Haixiu; Wang, Hua; Wu, Donglai

    2015-09-01

    Epizootic haemorrhagic disease is a non-contagious infectious viral disease of wild and domestic ruminants caused by epizootic hemorrhagic disease virus (EHDV). EHDV belongs to the genus Orbivirus within the family Reoviridae and is transmitted by insects of the genus Culicoides. The impact of epizootic haemorrhagic disease is underscored by its designation as a notifiable disease by the Office International des Epizooties. The EHDV genome consists of 10 linear dsRNA segments (Seg1-Seg10). Until now, no reverse genetics system (RGS) has been developed to generate replication-competent EHDV entirely from cloned cDNA, hampering detailed functional analyses of EHDV biology. Here, we report the generation of viable EHDV entirely from cloned cDNAs. A replication-competent EHDV-2 (Ibaraki BK13 strain) virus incorporating a marker mutation was rescued by transfection of BHK-21 cells with expression plasmids and in vitro synthesized RNA transcripts. Using this RGS, two additional modified EHDV-2 viruses were also generated: one that contained a duplex concatemeric Seg9 gene and another that contained a duplex concatemeric Seg10 gene. The modified EHDV-2 with a duplex Seg9 gene was genetically stable during serial passage in BHK-21 cells. In contrast, the modified EHDV-2 with a duplex Seg10 gene was unstable during serial passage, but displayed enhanced replication kinetics in vitro when compared with the WT virus. This RGS provides a new platform for the investigation of EHDV replication, pathogenesis and novel EHDV vaccines. PMID:25998915

  2. Genomic regulatory landscapes and chromosomal rearrangements

    DEFF Research Database (Denmark)

    Ladegaard, Elisabete L Engenheiro

    2008-01-01

    The main objectives of the PhD study are to identify and characterise chromosomal rearrangements within evolutionarily conserved regulatory landscapes around genes involved in the regulation of transcription and/or development (trans-dev genes). A frequent feature of trans-dev genes...... 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 tissue...... specificity of the individual CNEs. In this PhD study I have studied several chromosomal rearrangements with breakpoints in the vicinity of trans-dev genes. This included chromosomal rearrangements compatible with known phenotype-genotype associations (Rieger syndrome-PITX2, Mowat-Wilson syndrome-ZEB2...

  3. Degradations and Rearrangement Reactions

    Science.gov (United States)

    Zhang, Jianbo

    This section deals with recent reports concerning degradation and rearrangement reactions of free sugars as well as some glycosides. The transformations are classified in chemical and enzymatic ways. In addition, the Maillard reaction will be discussed as an example of degradation and rearrangement transformation and its application in current research in the fields of chemistry and biology.

  4. Identification of clonally rearranged T-cell receptor beta chain genes in HTLV-I carriers as a potential instrument for early detection of neoplasia

    Directory of Open Access Journals (Sweden)

    M.M. Sales

    2005-05-01

    Full Text Available We analyzed the genetic recombination pattern of the T-cell receptor beta-chain gene (TCR-beta in order to identify clonal expansion of T-lymphocytes in 17 human T-lymphotropic virus type I (HTLV-I-positive healthy carriers, 7 of them with abnormal features in the peripheral blood lymphocytes. Monoclonal or oligoclonal expansion of T-cells was detected in 5 of 7 HTLV-I-positive patients with abnormal lymphocytes and unconfirmed diagnosis by using PCR amplification of segments of TCR-beta gene, in a set of reactions that target 102 different variable (V segments, covering all members of the 24 V families available in the gene bank, including the more recently identified segments of the Vbeta-5 and Vbeta-8 family and the two diversity beta segments. Southern blots, the gold standard method to detect T-lymphocyte clonality, were negative for all of these 7 patients, what highlights the low sensitivity of this method that requires a large amount of very high quality DNA. To evaluate the performance of PCR in the detection of clonality we also analyzed 18 leukemia patients, all of whom tested positive. Clonal expansion was not detected in any of the negative controls or healthy carriers without abnormal lymphocytes. In conclusion, PCR amplification of segments of rearranged TCR-beta is reliable and highly suitable for the detection of small populations of clonal T-cells in asymptomatic HTLV-I carriers who present abnormal peripheral blood lymphocytes providing an additional instrument for following up these patients with potentially higher risk of leukemia.

  5. Identification of clonally rearranged T-cell receptor beta chain genes in HTLV-I carriers as a potential instrument for early detection of neoplasia.

    Science.gov (United States)

    Sales, M M; Bezerra, C N A; Hiraki, Y; Melo, N B; Rebouças, N A

    2005-05-01

    We analyzed the genetic recombination pattern of the T-cell receptor beta-chain gene (TCR-beta) in order to identify clonal expansion of T-lymphocytes in 17 human T-lymphotropic virus type I (HTLV-I)-positive healthy carriers, 7 of them with abnormal features in the peripheral blood lymphocytes. Monoclonal or oligoclonal expansion of T-cells was detected in 5 of 7 HTLV-I-positive patients with abnormal lymphocytes and unconfirmed diagnosis by using PCR amplification of segments of TCR-beta gene, in a set of reactions that target 102 different variable (V) segments, covering all members of the 24 V families available in the gene bank, including the more recently identified segments of the Vbeta-5 and Vbeta-8 family and the two diversity beta segments. Southern blots, the gold standard method to detect T-lymphocyte clonality, were negative for all of these 7 patients, what highlights the low sensitivity of this method that requires a large amount of very high quality DNA. To evaluate the performance of PCR in the detection of clonality we also analyzed 18 leukemia patients, all of whom tested positive. Clonal expansion was not detected in any of the negative controls or healthy carriers without abnormal lymphocytes. In conclusion, PCR amplification of segments of rearranged TCR-beta is reliable and highly suitable for the detection of small populations of clonal T-cells in asymptomatic HTLV-I carriers who present abnormal peripheral blood lymphocytes providing an additional instrument for following up these patients with potentially higher risk of leukemia. PMID:15917950

  6. ETS rearrangements in prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Mark A Rubin

    2012-01-01

    Prostate cancer is a clinically and molecularly heterogeneous disease.Understanding the biologic underpinning of prostate cancer is necessary to best determine how biology is associated with the risk of disease progression and how this understanding might provide insight into the development of novel therapeutic approaches.The focus of this review is on the recently identified common ETS and non-ETS gene rearrangements in prostate cancer.Although multiple molecular alterations have been detected in prostate cancer,a basic understanding of gene fusion prostate cancer should help explain the clinical and biologic diversity,providing a rationale for a molecular subclassification of the disease.

  7. PAX8 is transcribed aberrantly in cervical tumors and derived cell lines due to complex gene rearrangements.

    Science.gov (United States)

    López-Urrutia, Eduardo; Pedroza-Torres, Abraham; Fernández-Retana, Jorge; De Leon, David Cantu; Morales-González, Fermín; Jacobo-Herrera, Nadia; Peralta-Zaragoza, Oscar; García-Mendez, Jorge; García-Castillo, Verónica; Bautista-Isidro, Osvaldo; Pérez-Plasencia, Carlos

    2016-07-01

    The transcription factor PAX8, a member of the paired box-containing gene family with an important role in embryogenesis of the kidney, thyroid gland and nervous system, has been described as a biomarker in tumors of the thyroid, parathyroid, kidney and thymus. The PAX8 gene gives rise to four isoforms, through alternative mRNA splicing, but the splicing pattern in tumors is not yet established. Cervical cancer has a positive expression of PAX8; however, there is no available data determining which PAX8 isoform or isoforms are present in cervical cancer tissues as well as in cervical carcinoma-derived cell lines. Instead of a differential pattern of splicing isoforms, we found numerous previously unreported PAX8 aberrant transcripts ranging from 378 to 542 bases and present in both cervical carcinoma-derived cell lines and tumor samples. This is the first report of PAX8 aberrant transcript production in cervical cancer. Reported PAX8 isoforms possess differential transactivation properties; therefore, besides being a helpful marker for detection of cancer, PAX8 isoforms can plausibly exert differential regulation properties during carcinogenesis. PMID:27175788

  8. 特发性红皮病患者石蜡包埋组织TCRγ基因重排分析%TCRγ gene rearrangements in paraffin- embedded tissues from patients with idiopathic erythroderma

    Institute of Scientific and Technical Information of China (English)

    陈柳青; 陈金波; 段逸群; 李东升; 董碧麟; 张红梅

    2013-01-01

    Objective: To evaluate the values of TCRy gene rearrangement detected by BIOMED - 2 multiplex tubes TCRy (A+ B) in paraffin - embedded tissues from patients with idiopathic erythroderma. Methods: Twenty - eight DNA samples were extracted from paraffin - embedded multiplex tubes TCRy (A + B) in paraffin - embedded tissues from patients with idiopathic erythroderma. TCRy gene rearrangements were detected by BIOMED - 2 multiplex tubes TCRy (A+ B) and comparison with 28 patients with psoriasis vulgaris was made. Results: The positivity rate of TCRy gene rearrangements was 7.1% in samples from idiopathic erythroderma and none was positive in the patients with psoriasis vulgaris. Conclusion: Part of patients diagnosed as idiopathic erythroderma with positive clonal rearrangement of TCRy gene may develop into T cell lymphoma.%目的:检测特发性红皮病患者石蜡包埋皮肤组织T细胞受体(TCR)γ基因重排.方法:提取特发性红皮病患者石蜡包埋组织DNA 28份,利用BIOMED -2系统TCRγ引物组合进行TCRγ基因重排检测,以28例银屑病患者石蜡包埋组织作为阴性对照.结果:特发性红皮病患者石蜡包埋组织TCRγ基因重排阳性率为7.1%,对照组阳性率为0.结论:部分TCRγ基因重排阳性特发性红皮病患者可发展成T细胞淋巴瘤.

  9. Identification of IgH gene rearrangement and immunophenotype in an animal model of Epstein-Barr virus-associated lymphomas.

    Science.gov (United States)

    Zhang, Yang; Peng, Xueqin; Tang, Yunlian; Gan, Xiaoning; Wang, Chengkun; Xie, Lu; Xie, Xiaoli; Gan, Runliang; Wu, Yimou

    2016-10-01

    Epstein-Barr virus (EBV) is a human oncogenic herpesvirus associated with lymphoma and nasopharyngeal carcinoma. Because the susceptible hosts of EB virus are limited to human and cotton-top tamarins (Saguinus oedipus), there have been no appropriate animal models until the lymphoma model induced by EBV in human peripheral blood lymphocyte (hu-PBL)/SCID chimeric mice was reported. However, it is still controversial whether the EBV-associated lymphoma induced in hu-PBL/SCID mice is a monoclonal tumor. In this study, we transplanted normal human peripheral blood lymphocytes (hu-PBL) from six donors infected with EBV into SCID mice to construct hu-PBL/SCID chimeric mice. The induced tumors were found in the mediastinum or abdominal cavity of SCID mice. Microscopic observation exhibited tumor cells that were large and had a plasmablastic, centroblastic or immunoblastic-like appearance. Immunophenotyping assays showed the induced tumors were LCA-positive, CD20/CD79a-positive (markers of B cells), and CD3/CD45RO-negative (markers of T cells). A human-specific Alu sequence could be amplified by Alu-PCR. This confirmed that induced tumors were B-cell lymphomas originating from the transplanted human lymphocytes rather than mouse cells. EBER in situ hybridization detected positive signals in the nuclei of the tumor cells. Expression of EBV-encoded LMP1, EBNA-1, and EBNA-2 in the tumors was significantly positive. PCR-based capillary electrophoresis analysis of IgH gene rearrangement revealed a monoclonal peak and single amplification product in all six cases of induced tumors. This indicated that EBV can induce monoclonal proliferation of human B lymphocytes and promotes the development of lymphoma. J. Med. Virol. 88:1804-1813, 2016. © 2016 Wiley Periodicals, Inc. PMID:26991077

  10. Rearrangements of Cycloalkenyl Aryl Ethers

    Directory of Open Access Journals (Sweden)

    Mercedesz Törincsi

    2016-04-01

    Full Text Available Rearrangement reactions of cycloalkenyl phenol and naphthyl ethers and the acid-catalyzed cyclization of the resulting product were investigated. Claisen rearrangement afforded 2-substituted phenol and naphthol derivatives. Combined Claisen and Cope rearrangement resulted in the formation of 4-substituted phenol and naphthol derivatives. In the case of cycloocthylphenyl ether the consecutive Claisen and Cope rearrangements were followed by an alkyl migration. The mechanism of this novel rearrangement reaction is also discussed.

  11. Solitary plasmacytoma of bone: a clinicopathologic, immunohistochemical and immunoglobulin gene rearrangement study%骨孤立性浆细胞瘤的临床病理分析

    Institute of Scientific and Technical Information of China (English)

    左卓; 刘卫平; 唐源; 毕成峰; 王晓卿; 张文燕; 杨群培; 邹立群

    2010-01-01

    目的 探讨骨孤立性浆细胞瘤(SPB)的临床病理特征,了解免疫表型在SPB的病理诊断和鉴别诊断中的意义和作用.方法 收集1990-2008年21例SPB的临床病理资料并进行回顾性分析,应用免疫组织化学(EnVision或EliVision法)检测17种抗原的表达情况,并用半套式PCR技术,以免疫球蛋白重链通用型引物,以及BIOMED-2系统引物IgK和IgL进行免疫球蛋白基因重排检测.结果 21例SPB患者年龄36~72岁,中位年龄50岁.主要病变部位为中轴骨骼(14例,66.7%),其次为四肢骨骼(7例,33.3%).5例有血清Ig升高,其中3例为IgA型,2例为IgG型.临床表现与肿瘤部位有关,有局部疼痛、脊神经压迫征和病理性骨折等.所有病例均表现为局部孤立性占位病变伴骨质破坏.组织学分级:21例中Ⅰ、Ⅱ和Ⅲ级者分别为12例(57.1%)、5例(23.8%)和4例(19.0%).免疫表型:所有病例之瘤细胞均表达两种及以上浆细胞抗原,如CD138、CD38和浆细胞抗体;均不表达CD19和CD20,CD79a表达率为23.8%(5/21).CD56、CD27和CD44v6的表达率分别为57.1%(12/21)、15.0%(3/20)和23.8%(5/21).21例SPB中12例(57.1%)检出IgH基因克隆性重排.12例(57.1%)有随访,7例死亡,5例存活;其中3例发展为多发性骨髓瘤并已死亡.结论 SPB以骨的孤立性占位伴疼痛为其临床特征,诊断需排除多发性骨髓瘤髓外浸润之可能.免疫表型及Ig基因重排检测在该肿瘤的诊断中起重要作用.%Objective To investigate clinicopathologic features of solitary plasmacytoma of bone(SPB) and the role of immuno-phenotype and immunoglobulin gene rearrangement detection in the diagnosis and differential diagnosis of SPB.Methods A total of 21 cases of SPB were selected during a period from 1990 to 2008.A retrospective clinicopathologic study and immunohistochemistry (EnVision or EliVision methods) of 17 antigens were performed.In addition, universal IgH (FR3A/LJH/VLJH) primers and BIOMED-2 PCR multiplex tubes were

  12. Molecular Insights in MLL Rearranged Acute Leukemia

    NARCIS (Netherlands)

    R.W. Stam (Ronald)

    2006-01-01

    textabstractAcute lymphoblastic leukemia (ALL) in infants (<1 year of age) is characterized by a high incidence (~80%) of rearrangements of the MLL gene, resistance to several important chemotherapeutic drugs, and a poor treatment outcome. With overall survival rates for infant ALL not exceeding 50%

  13. The structure, rearrangement, and ontogenic expression of DB and JB gene segments of the Mexican axolotl T-cell antigen receptor beta chain (TCRB).

    Science.gov (United States)

    Kerfourn, F; Charlemagne, J; Fellah, J S

    1996-01-01

    We sequenced a total of 189 independent rearrangements in which the VB7.1 element is associated with CB1 (99 clones) or CB2 (90 clones) isotypes of the T-cell receptor (TCR) beta chain in the Mexican axolotl. Three stages of development were analyzed: 2.5 months, 10 months, and 25 months. Three JB1 segments were associated with the VB-CB1 rearrangements and six JB2 segments with VB-CB2. As in other vertebrates, some amino acid positions were conserved in all Jbetas (e. g., Phe-108, Gly-109, Gly-111, Thr-112, and Val-116). Two 11 nucleotides DB-like sequences, differed by one (A or T) central residue and could be productively read in the three putative reading frames. Most of the DB1 and JB1 segments were in the VB-CB1 clones, and most of the DB2 and JB2 segments were in the VB-CB2 clones, suggesting that the TCRB locus is organized into independent DB-JB-CB clusters that used the same collection of VB segments. About 40% of the beta-chain VDJ junctions in 2.5-month-old larvae had N nucleotides, compared with about 73% in 10 - 25-month old animals. The beta-chain VDJ junctions had about 30% of defective rearrangements at all stages of development, which could be due to the slow rate of cell division in the axolotl lymphoid organs, and the large genome in this urodele. Many of the axolotl CDRbeta3 sequences deduced for in frame VDJ rearrangements are the same in animals of different origins. Such redundancy could be a statistical effect due to the small number of thymocytes in the developing axolotl, rather than to some bias due to junctional preferences.

  14. The structure, rearrangement, and ontogenic expression of DB and JB gene segments of the Mexican axolotl T-cell antigen receptor beta chain (TCRB).

    Science.gov (United States)

    Kerfourn, F; Charlemagne, J; Fellah, J S

    1996-01-01

    We sequenced a total of 189 independent rearrangements in which the VB7.1 element is associated with CB1 (99 clones) or CB2 (90 clones) isotypes of the T-cell receptor (TCR) beta chain in the Mexican axolotl. Three stages of development were analyzed: 2.5 months, 10 months, and 25 months. Three JB1 segments were associated with the VB-CB1 rearrangements and six JB2 segments with VB-CB2. As in other vertebrates, some amino acid positions were conserved in all Jbetas (e. g., Phe-108, Gly-109, Gly-111, Thr-112, and Val-116). Two 11 nucleotides DB-like sequences, differed by one (A or T) central residue and could be productively read in the three putative reading frames. Most of the DB1 and JB1 segments were in the VB-CB1 clones, and most of the DB2 and JB2 segments were in the VB-CB2 clones, suggesting that the TCRB locus is organized into independent DB-JB-CB clusters that used the same collection of VB segments. About 40% of the beta-chain VDJ junctions in 2.5-month-old larvae had N nucleotides, compared with about 73% in 10 - 25-month old animals. The beta-chain VDJ junctions had about 30% of defective rearrangements at all stages of development, which could be due to the slow rate of cell division in the axolotl lymphoid organs, and the large genome in this urodele. Many of the axolotl CDRbeta3 sequences deduced for in frame VDJ rearrangements are the same in animals of different origins. Such redundancy could be a statistical effect due to the small number of thymocytes in the developing axolotl, rather than to some bias due to junctional preferences. PMID:8753858

  15. Rearrangement of endogenous ecotropic proviral gene and interleukin-3 gene in radiation-induced myeloid leukemias of RFM/Un mice

    International Nuclear Information System (INIS)

    With the consideration that RFM/Un mice harbor on their chromosome 5 an ecotropic provirus locus for producing murine leukemia viruses (e-MuLV) and that interleukin-3 (IL-3) plays important roles in the growth and differentiation regulation of hematopoietic cells, particularly the myeloid lineages, they have examined radiation-induced myeloid leukemias of these mice for possible alterations in these two genes. Southern gel blot in combination with restriction enzyme analyses were performed with the use of an ecotropic env-specific sequence and an IL-3 cDNA clone as molecular probes. It was found that the transplantable Upton myeloid leukemia line has lost the chromosome 5 (germline) provirus and, instead, contains at least 4 copies of e-MuLV proviral sequences that have been acquired apparently by somatic re-integration. DNA preparations from 4 leukemic spleens of X-irradiated RFM/Un male mice, diagnosed histologically to have developed myeloid leukemias, were therefore examined; all four showed no loss of the germline e-MuLV copy and two of the four contained additional somatically re-integrated e-MuLV proviruses

  16. Rearrangements in ground and excited states

    CERN Document Server

    de Mayo, Paul

    1980-01-01

    Rearrangements in Ground and Excited States, Volume 2 covers essays on the theoretical approach of rearrangements; the rearrangements involving boron; and the molecular rearrangements of organosilicon compounds. The book also includes essays on the polytopal rearrangement at phosphorus; the rearrangement in coordination complexes; and the reversible thermal intramolecular rearrangements of metal carbonyls. Chemists and people involved in the study of rearrangements will find the book invaluable.

  17. Rearrangements in ground and excited states

    CERN Document Server

    de Mayo, Paul

    1980-01-01

    Rearrangements in Ground and Excited States, Volume 3 presents essays on the chemical generation of excited states; the cis-trans isomerization of olefins; and the photochemical rearrangements in trienes. The book also includes essays on the zimmerman rearrangements; the photochemical rearrangements of enones; the photochemical rearrangements of conjugated cyclic dienones; and the rearrangements of the benzene ring. Essays on the photo rearrangements via biradicals of simple carbonyl compounds; the photochemical rearrangements involving three-membered rings or five-membered ring heterocycles;

  18. Chromosome rearrangements and transposable elements.

    Science.gov (United States)

    Lonnig, Wolf-Ekkehard; Saedler, Heinz

    2002-01-01

    There has been limited corroboration to date for McClintock's vision of gene regulation by transposable elements (TEs), although her proposition on the origin of species by TE-induced complex chromosome reorganizations in combination with gene mutations, i.e., the involvement of both factors in relatively sudden formations of species in many plant and animal genera, has been more promising. Moreover, resolution is in sight for several seemingly contradictory phenomena such as the endless reshuffling of chromosome structures and gene sequences versus synteny and the constancy of living fossils (or stasis in general). Recent wide-ranging investigations have confirmed and enlarged the number of earlier cases of TE target site selection (hot spots for TE integration), implying preestablished rather than accidental chromosome rearrangements for nonhomologous recombination of host DNA. The possibility of a partly predetermined generation of biodiversity and new species is discussed. The views of several leading transposon experts on the rather abrupt origin of new species have not been synthesized into the macroevolutionary theory of the punctuated equilibrium school of paleontology inferred from thoroughly consistent features of the fossil record. PMID:12429698

  19. BIOMED-2引物系统检测 T 淋巴母细胞性淋巴瘤/急性淋巴细胞白血病中Ig/TCR基因重排%Detection of immunoglobulin and TCR gene rearrangements by PCR using BIOMED-2 multi-plex protocols in T lymphoblastie lymphoma and acute lymphoblastic leukemia

    Institute of Scientific and Technical Information of China (English)

    潘鑫艳; 冯强; 黎贵芸; 杨长绍; 杨举伦; 王丽

    2015-01-01

    目的:探讨BIOMED-2引物系统检测T淋巴母细胞性淋巴瘤( T lymphoblastic lymphoma, T-LBL)/急性淋巴细胞白血病( acute lymphoblastic leukemia, ALL)患者免疫球蛋白( immunoglobulin, Ig)/T细胞受体基因( T-cell receptor, TCR)重排的敏感性,分析Ig/TCR基因重排方式。方法采用BIOMED-2引物系统扩增35例T-LBL/ALL中Ig/TCR重排基因,核酸分子异源双链凝胶电泳分析基因重排结果。结果35例T-LBL/ALL中16例检测出TCR基因重排,检出率为45.7%,其中TCRβ单重排6例(37.5%),TCRγ单重排4例(25.0%),TCRβ和 TCRγ双重排3例(18.8%),TCRδ单重排2例(12.5%),TCRγ和TCRδ双重排1例(6.3%)。4例患者同时检测出Ig和TCR基因重排,Ig基因检出率为11.4%。28例T-LBL中11例检测出TCR基因重排(39.3%),7例T-ALL中6例检测出TCR基因重排(85.7%)。结论利用BIOMED-2引物系统可检测出部分T-LBL患者的Ig/TCR基因重排,是一种辅助诊断工具。%Purpose To investigate the sensitivity of BIOMED-2 primer system in T lymphoblastic lymphoma ( T-LBL) and acute lym-phoblastic leukemia ( ALL) patients immunoglobulin ( Ig) and T-cell receptor ( TCR) gene rearrangement, and to analyze the co-rear-rangement pattern. Methods Amplification of rearranged Ig and TCR gene was performed in standard PCR in 35 T-LBL/ALL pa-tients. PCR products were analyzed by heteroduplex and polyacrylamide gel electrophoresis. Results 16 cases (45. 7%) of 35 sam-ples were detected to have TCR gene rearrangements, including 6 cases (37. 5%) of TCRβgene monoclonal rearrangements, 4 cases (25. 0%) of TCRγ gene monoclonal rearrangements, 3 cases (18. 8%) of TCRβ and TCRγ gene double rearrangements, 2 cases (12. 5%) of TCRδ gene monoclonal rearrangements and 1 case (6. 3%) of TCRγand TCRδgene double rearrangements were detec-ted. 4 cases (11. 4%) of 35 samples detected to have clonal immunoglobulin and TCR gene rearrangements. 11 cases (39. 3%) of 28 T-LBL patients were detected to

  20. Significance of myc gene rearrangement and its correlation with prognosis in diffuse large B cell lymphoma%弥漫性大B细胞淋巴瘤中myc基因重排及其临床意义

    Institute of Scientific and Technical Information of China (English)

    张宏伟; 陈振文; 贺建霞; 郑玉萍; 韩维娥; 赵志强; 白玮; 王晋芬

    2013-01-01

    Objective To study the relationship between myc gene rearrangement and myc protein expression in diffuse large B cell lymphoma (DLBCL),and their correlation with prognosis.Methods One hundred and six cases of DLBCLs with follow-up data were analyzed using interphase fluorescence in situ hybridization (FISH) technique.Immunophenotyping analysis for CD20,CD3,myc,Mum-1,CD10,bcl-6 was also performed using EnVision immunohistochemistry.Results The percentages of tumor cells expressing myc,Mum-1,CD10 and bcl-6 were 70.8%,56.6%,21.7% and 26.4%,respectively.Twenty six cases(24.5%)were of GCB type and the rest(75.5%)were of non-GCB (non germinal center) type.The myc rearrangement was identified in 13 (12.3%) of 106 cases.13 cases showed to be of non-GCB type.There was no correlation between myc rearrangement and myc protein expression.DLBCLs (n =13) with myc rearrangement showed significantly poorer overall survival (OS) and progression free survival (PFS),with a median OS and PFS time of 4.7 and 3.2 months,respectively (for OS and PFS,P <0.001).Multivariate analysis using Cox proportional hazard model confirmed that myc rearrangement,ECOG performance status of 2-4,immunophenotyping subgroup and myc protein were independent factors affecting the prognosis and significantly associated with the survival.However,myc rearrangement was the strongest prognostic factor.Conclusions DLBCL with myc gene rearrangement is a subgroup of non-GCB DLBCL with poor outcome.It is an independent and useful factor for prognosis in DLBCL.Expression of myc is influenced by many factors and myc rearrangement may be one of these factors.%目的 探讨弥漫性大B细胞淋巴瘤(DLBCL)中myc基因重排和蛋白表达及其与预后的相关性.方法 采用免疫组织化学EnVision法检测106例DLBCL患者肿瘤组织中CD3、CD10、CD20、bcl-6、多发性骨髓瘤原癌基因1(Mum-1)和myc蛋白的表达情况,采用荧光原位杂交(FISH)技术检测myc基因重排.结果 106

  1. Pulmonary lymphomatoid granulomatosis: an immunohistochemical and gene rearrangement study%肺淋巴瘤样肉芽肿病的免疫表型及基因重排研究

    Institute of Scientific and Technical Information of China (English)

    冯瑞娥; 刘鸿瑞; 刘彤华; 陈杰; 凌庆; 师晓华; 钟定荣; 罗玉风; 曹金伶

    2011-01-01

    目的 观察肺淋巴瘤样肉芽肿病的细胞组成、免疫表型和分子生物学改变.方法 回顾性分析北京协和医院9例肺淋巴瘤样肉芽肿病患者的临床病理情况.其中5例为开胸肺活检标本,3例为肺叶切除标本,1例尸检.标本经4%甲醛固定,石蜡包埋,常规切片,HE染色.免疫组织化学EnVision法染色(抗体包括CD20、CD3、CD56),原位杂交检测EB病毒,采用聚合酶链反应进行Ig和TCR基因重排检测.结果 9例肺淋巴瘤样肉芽肿患者,年龄3~59岁,男∶女=3:6.9例患者肺组织内病变分布均显示以血管为中心的淋巴细胞浸润为特点.免疫组织化学显示以CD3阳性的T淋巴细胞占绝对优势,散在不等数量的CD20阳性的B细胞,CD56均为阴性.8例行EB病毒原位杂交,4例阳性细胞数20%,1例为15%.按照WHO的3级分级方法,Ⅰ级为4例,Ⅱ级1例,Ⅲ级4例.6例行基因重排检测,3例显示有Ig基因重排阳性,其中,1例为Ⅱ级病变,2例为Ⅲ级病变.6例TCR重排检测均为阴性.随访时间0.5~6.5年不等,9例患者中3例死亡,2例存活,4例失访.结论 部分肺淋巴瘤样肉芽肿病,特别是Ⅱ、Ⅲ级患者,有B淋巴细胞克隆性增生,提示其为淋巴瘤性病变.%Objective To study the immunophenotype and gene rearrangement pattern of pulmonary lymphomatoid granulomatosis. Methods Nine cases of pulmonary lymphomatoid granulomatosis, included 5 cases of open lung biopsy, 3 cases of lobectomy specimen and 1 case of autopsy, were retrospectively analyzed by immunohistochemistry, in-situ hybridization for Epstein-Barr virus-encoded RNA, immunoglobulin and T-cell receptor gene rearrangement studies. Results The Histologically, all cases showed lymphocytic infiltration surrounding the blood vessels and in the perivascular areas. Most of these lymphoid cells expressed T-cell marker CD3. There were also variable numbers of CD20-positive B cells. The staining for CD56 was negative. According to the WHO

  2. Complete mtDNA sequences of two millipedes suggest a new model for mitochondrial gene rearrangements: Duplication and non-random loss

    Energy Technology Data Exchange (ETDEWEB)

    Lavrov, Dennis V.; Boore, Jeffrey L.; Brown, Wesley M.

    2001-11-08

    We determined the complete mtDNA sequences of the millipedes Narceus annularus and Thyropygus sp. (Arthropoda: Diplopoda) and identified in both genomes all 37 genes typical for metazoan mtDNA. The arrangement of these genes is identical in the two millipedes, but differs from that inferred to be ancestral for arthropods by the location of four genes/gene clusters. This novel gene arrangement is unusual for animal mtDNA, in that genes with opposite transcriptional polarities are clustered in the genome and the two clusters are separated by two non-coding regions. The only exception to this pattern is the gene for cysteine tRNA, which is located in the part of the genome that otherwise contains all genes with the opposite transcriptional polarity. We suggest that a mechanism involving complete mtDNA duplication followed by the loss of genes, predetermined by their transcriptional polarity and location in the genome, could generate this gene arrangement from the one ancestral for arthropods. The proposed mechanism has important implications for phylogenetic inferences that are drawn on the basis of gene arrangement comparisons.

  3. [Dose-Response Dependences for Frequency of RET/PTC Gene Rearrangements in Papillary Thyroid Carcinoma after Irradiation. Simple Pooling Analysis of Molecular Epidemiological Data].

    Science.gov (United States)

    Koterov, A N; Ushenkova, L N; Biryukov, A P

    2016-01-01

    On the basis of all possible publications on the theme included in the previously formed base of sources on molecular epidemiology of RET/PTC rearrangements in thyroid papillary carcinoma a pooled analysis ("simple pooling data") on determination of the dose-effect dependences for RET/PTC frequency in radiogenic carcinomas of various irradiated groups was performed. (They are groups subjected to radiotherapeutic exposure, residents near the Chernobyl nuclear power plant (CNPP) and victims of nuclear bombing). The tendency to Pearson linear correlation (r = 0.746; p = 0.148) between the frequency of RET/PTC and the estimated dose on thyroid in the regions affected by the CNPP accident was revealed. But this tendency was recognized to be random owing to abnormally low values of the indicator for the most contaminated Gomel region. The method tentatively called "case-control" showed reliable differences in thyroid dose values for carcinomas with RET/PTC and without those. The versatility of changes was found: the lack of RET/PTC for radiotherapeutic impacts was associated with higher doses, whereas in case of the CNPP accident and for nuclear bombing victims it was the opposite. Probably, in the first case the "cellular cleaning" phenomenon after exposure to very high doses took place. Search of direct Pearson correlations between average/median thyroid doses on groups and RET/PTC frequency in carcinomas of these groups showed a high reliability for the dose-effect dependences- at the continuous dose scale (for RET/PTC in total and RET/PTC1 respectively: r = 0.830; p = 0.002 and r = 0.906; p = 0.0003); while there was no significant correlation received for RET/PTC3. When using the weighting least square regression analysis (proceeding from the number of carcinomas in samples), the specified regularities remained. Attempts to influence the strength of correlation by exception ofthe data of all the samples connected with the accident on the CNPP did not significantly

  4. Anaplastic lymphoma kinase gene rearrangements in patients with advanced-stage non-small-cell lung cancer: CT characteristics and response to chemotherapy

    International Nuclear Information System (INIS)

    Few articles have been published on the imaging findings of anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC). To investigate the radiological findings of ALK-positive NSCLC in the advanced stage, CT scans were examined. In addition, the response to chemotherapy was evaluated. Of the 36 patients with ALK-rearranged NSCLC, a mass and a nodule were identified in 17 (47.2%) and 16 (44.4%), respectively, indicating that more than 40% had a small-sized tumor. Overall, 31 (86.1%) patients had lymphadenopathy, seven (19.4%) had extranodal lymph node invasion, and three (8.3%) had lymphangitis. A pleural effusion was seen in 15 patients (41.7%). All but one patient had no ground-glass opacity (GGO) lesions, indicating that most ALK-positive tumors showed a solid growth pattern without GGO on CT. Twenty were evaluable for response to chemotherapy; 10 (50.0%) had a partial response (PR), nine (45.0%) had stable disease (SD), and one (5.0%) had progressive disease (PD) with first-line chemotherapy. With second-line chemotherapy, five (26.3%) had PR, 11 (57.9%) had SD, and three (15.8%) had PD. The five patients with PR were all treated by using crizotinib. Time to progression was 8.2 months with first-line chemotherapy, and 6.0 months with second-line chemotherapy. Advanced-stage ALK-positive tumors have a relatively aggressive phenotype, which cannot be inferred from the size of the tumor alone. ALK-positive patients have a good response to first-line cytotoxic drugs and to crizotinib as second-line therapy, but a relatively poor response to cytotoxic drugs as second-line therapy

  5. Analysis of gene order data supports vertical inheritance of the leukotoxin operon and genome rearrangements in the 5' flanking region in genus Mannheimia

    DEFF Research Database (Denmark)

    Larsen, Jesper; Kuhnert, Peter; Frey, Joachim;

    2007-01-01

    examined the gene order in the 5' flanking region of the leukotoxin operon and found that the 5' flanking gene strings, hslVU-lapB-artJ-lktC and xylAB-lktC, are peculiar to M. haemolytica + M. glucosida and M. granulomatis, respectively, whereas the gene string hslVU-lapB-lktC is present in M. ruminalis......, the supposed sister group of M. haemolytica + M. glucosida, and in the most ancient subclade M. varigena. In M. granulomatis, we found remnants of the gene string hslVU-lapB-lktC in the xylB-lktC intergenic region. CONCLUSIONS: These observations indicate that the gene string hslVU-lapB-lktC is more ancient...... than the hslVU-lapB-artJ-lktC and xylAB-lktC gene strings. The presence of (remnants of) the ancient gene string hslVU-lapB-lktC among any subclades within genus Mannheimia supports that it has been vertically inherited from the last common ancestor of genus Mannheimia to any ancestor of the diverging...

  6. Mitochondrial gene rearrangement and molecular marker selection for Odontobutis potamophila%河川沙塘鳢线粒体基因组重排机制及分子标记筛选

    Institute of Scientific and Technical Information of China (English)

    李强; 刘至治; 顾珈宁

    2015-01-01

    采用引物步移法PCR扩增,获得全长为16846 bp 的河川沙塘鳢(Odontobutis potamophila)线粒体全基因组DNA (mtDNA),并对其基因结构、重排机制及在系统发育中的应用进行了分析。研究结果:(1)河川沙塘鳢mtDNA由37个基因和1个非编码控制区组成;除 ND6和8个 tRNA 外,其他基因都编码在重链(H)上; tRNA 基因因发生滑移重排(shuffling),将经典的线粒体基因组 HSL (tRNAHis–tRNASer–tRNALeu)排列变成了 SLH (tRNASer–tRNALeu–tRNAHis)排列,造成在tRNALeu与tRNAHis、ND4与tRNASer之间分别插入了320 bp和42 bp的两个“匿名区”。(2)检测的112种鲈形目(Perciformes)鱼类中,仅有13种(11.61%)发生了mtDNA基因重排现象,而沙塘鳢属的中华沙塘鳢(O. sinensis)、平头沙塘鳢(O. platycephala)与河川沙塘鳢的基因重排位置一致,揭示其可能是沙塘鳢属鱼类进化过程中的一个重要分子“标签”。(3)筛选得到的两个分子标记ND4和ND5基因,适合用于虾虎鱼亚目(Gobioidei)鱼类科阶元水平的系统发育关系的重建。%The river sleeper, Odontobutis potamophila (Perciformes, Odontobutidae), is a small demersal freshwa-ter goby and has recently been considered a promising candidate for aquaculture in China. However, until now there has been limited genetic information regarding O. potamophila. In this paper, the complete mitochondrial genome (mtDNA) of O. potamophila was obtained by primer-walking PCR amplification, and the mtDNA length was 16846 bp. Then, mtDNA structure, gene rearrangement mechanism, and application in phylogenetic recon-struction were analyzed. The mtDNA of O. potamophila contained 37 genes (13 protein-coding genes, two rRNAs, and 22 tRNAs) and non-coding control regions. In addition to ND6 and eight tRNAs (tRNAGln, tRNAAla, tRNAAsn, tRNACys, tRNATyr, tRNASer, tRNAGlu, and tRNAPro), all other components were encoded on the heavy strand. All protein-coding genes initiated

  7. Claisen thermally rearranged (CTR) polymers

    Science.gov (United States)

    Tena, Alberto; Rangou, Sofia; Shishatskiy, Sergey; Filiz, Volkan; Abetz, Volker

    2016-01-01

    Thermally rearranged (TR) polymers, which are considered the next-generation of membrane materials because of their excellent transport properties and high thermal and chemical stability, are proven to have significant drawbacks because of the high temperature required for the rearrangement and low degree of conversion during this process. We demonstrate that using a [3,3]-sigmatropic rearrangement, the temperature required for the rearrangement of a solid glassy polymer was reduced by 200°C. Conversions of functionalized polyimide to polybenzoxazole of more than 97% were achieved. These highly mechanically stable polymers were almost five times more permeable and had more than two times higher degrees of conversion than the reference polymer treated under the same conditions. Properties of these second-generation TR polymers provide the possibility of preparing efficient polymer membranes in a form of, for example, thin-film composite membranes for various gas and liquid membrane separation applications.

  8. A rearrangement of the Z chromosome topology influences the sex-linked gene display in the European corn borer, Ostrinia nubilalis

    Science.gov (United States)

    The sex determination system of Lepidoptera is comprised of heterogametic females (ZW) and homogametic males (ZZ), where voltinism (Volt) and the male pheromone response traits (Resp) are controlled by genes housed on the Z-chromosome. Volt and Resp determine traits that lead to ecotype differentia...

  9. Characterization of the T-cell receptor gamma chain gene rearrangements as an adjunct tool in the diagnosis of T-cell lymphomas in the gastrointestinal tract of cats.

    Science.gov (United States)

    Gress, Verena; Wolfesberger, Birgitt; Fuchs-Baumgartinger, Andrea; Nedorost, Nora; Saalmüller, Armin; Schwendenwein, Ilse; Rütgen, Barbara C; Hammer, Sabine E

    2016-08-01

    Feline alimentary lymphoma is the most common hematopoietic neoplasia in cats. It affects mainly the small intestines and is most frequently of T-cell origin. Evaluation of a fine needle aspirate is often the first step in the diagnostic work-up. Differentiation between a resident mature lymphocyte population as encountered in inflammatory bowel disease and small cell lymphoma cannot be achieved by cytology alone. Even full thickness biopsies evaluated by histopathology can be inconclusive. These cases warrant the application of complementary tools like PCR-based T-cell receptor (TCR) clonality testing for confirmation. The aim of this study was to optimize the DNA extraction protocol for formalin fixed and paraffin embedded tissues (FFPE) and to establish a heteroduplex analysis to enhance resolution of the PCR fragments of the T-cell receptor gamma (TCRG) V-J gene. The new protocols resulted in improved quantity and quality of the extracted DNA. Heteroduplex analysis of the samples improved the resolution of the electrophoresis results so that rules for interpretation of the different patterns could be established. Application of this improved setup detected clonal rearrangements in at least one TCRG primer reaction in 31 of 36 of our feline intestinal lymphoma samples after DNA quality testing. PMID:27474005

  10. Characterization of the T-cell receptor gamma chain gene rearrangements as an adjunct tool in the diagnosis of T-cell lymphomas in the gastrointestinal tract of cats.

    Science.gov (United States)

    Gress, Verena; Wolfesberger, Birgitt; Fuchs-Baumgartinger, Andrea; Nedorost, Nora; Saalmüller, Armin; Schwendenwein, Ilse; Rütgen, Barbara C; Hammer, Sabine E

    2016-08-01

    Feline alimentary lymphoma is the most common hematopoietic neoplasia in cats. It affects mainly the small intestines and is most frequently of T-cell origin. Evaluation of a fine needle aspirate is often the first step in the diagnostic work-up. Differentiation between a resident mature lymphocyte population as encountered in inflammatory bowel disease and small cell lymphoma cannot be achieved by cytology alone. Even full thickness biopsies evaluated by histopathology can be inconclusive. These cases warrant the application of complementary tools like PCR-based T-cell receptor (TCR) clonality testing for confirmation. The aim of this study was to optimize the DNA extraction protocol for formalin fixed and paraffin embedded tissues (FFPE) and to establish a heteroduplex analysis to enhance resolution of the PCR fragments of the T-cell receptor gamma (TCRG) V-J gene. The new protocols resulted in improved quantity and quality of the extracted DNA. Heteroduplex analysis of the samples improved the resolution of the electrophoresis results so that rules for interpretation of the different patterns could be established. Application of this improved setup detected clonal rearrangements in at least one TCRG primer reaction in 31 of 36 of our feline intestinal lymphoma samples after DNA quality testing.

  11. Clonality Analysis of Immunoglobulin Gene Rearrangement by Next-Generation Sequencing in Endemic Burkitt Lymphoma Suggests Antigen Drive Activation of BCR as Opposed to Sporadic Burkitt Lymphoma

    Science.gov (United States)

    Amato, Teresa; Abate, Francesco; Piccaluga, Pierpaolo; Iacono, Michele; Fallerini, Chiara; Renieri, Alessandra; De Falco, Giulia; Ambrosio, Maria Raffaella; Mourmouras, Vaselious; Ogwang, Martin; Calbi, Valeria; Rabadan, Roul; Hummel, Michael; Pileri, Stefano; Bellan, Cristiana

    2016-01-01

    Objectives: Recent studies using next-generation sequencing (NGS) analysis disclosed the importance of the intrinsic activation of the B-cell receptor (BCR) pathway in the pathogenesis of sporadic Burkitt lymphoma (sBL) due to mutations of TCF3/ID3 genes. Since no definitive data are available on the genetic landscape of endemic Burkitt (eBL), we first assessed the mutation frequency of TCF3/ID3 in eBL compared with sBL and subsequently the somatic hypermutation status of the BCR to answer whether an extrinsic activation of BCR signaling could also be demonstrated in Burkitt lymphoma. Methods: We assessed the mutations of TCF3/ID3 by RNAseq and the BCR status by NGS analysis of the immunoglobulin genes (IGs). Results: We detected mutations of TCF3/ID3 in about 30% of the eBL cases. This rate is significantly lower than that detected in sBL (64%). The NGS analysis of IGs revealed intraclonal diversity, suggesting an active targeted somatic hypermutation process in eBL compared with sBL. Conclusions: These findings support the view that the antigenic pressure plays a key role in the pathogenetic pathways of eBL, which may be partially distinct from those driving sBL development. PMID:26712879

  12. Rearrangement and evolution of mitochondrial genomes in parrots.

    Science.gov (United States)

    Eberhard, Jessica R; Wright, Timothy F

    2016-01-01

    Mitochondrial genome rearrangements that result in control region duplication have been described for a variety of birds, but the mechanisms leading to their appearance and maintenance remain unclear, and their effect on sequence evolution has not been explored. A recent survey of mitochondrial genomes in the Psittaciformes (parrots) found that control region duplications have arisen independently at least six times across the order. We analyzed complete mitochondrial genome sequences from 20 parrot species, including representatives of each lineage with control region duplications, to document the gene order changes and to examine effects of genome rearrangements on patterns of sequence evolution. The gene order previously reported for Amazona parrots was found for four of the six independently derived genome rearrangements, and a previously undescribed gene order was found in Prioniturus luconensis, representing a fifth clade with rearranged genomes; the gene order resulting from the remaining rearrangement event could not be confirmed. In all rearranged genomes, two copies of the control region are present and are very similar at the sequence level, while duplicates of the other genes involved in the rearrangement show signs of degeneration or have been lost altogether. We compared rates of sequence evolution in genomes with and without control region duplications and did not find a consistent acceleration or deceleration associated with the duplications. This could be due to the fact that most of the genome rearrangement events in parrots are ancient, and additionally, to an effect of body size on evolutionary rate that we found for mitochondrial but not nuclear sequences. Base composition analyses found that relative to other birds, parrots have unusually strong compositional asymmetry (AT- and GC-skew) in their coding sequences, especially at fourfold degenerate sites. Furthermore, we found higher AT skew in species with control region duplications. One

  13. Rearrangement and evolution of mitochondrial genomes in parrots.

    Science.gov (United States)

    Eberhard, Jessica R; Wright, Timothy F

    2016-01-01

    Mitochondrial genome rearrangements that result in control region duplication have been described for a variety of birds, but the mechanisms leading to their appearance and maintenance remain unclear, and their effect on sequence evolution has not been explored. A recent survey of mitochondrial genomes in the Psittaciformes (parrots) found that control region duplications have arisen independently at least six times across the order. We analyzed complete mitochondrial genome sequences from 20 parrot species, including representatives of each lineage with control region duplications, to document the gene order changes and to examine effects of genome rearrangements on patterns of sequence evolution. The gene order previously reported for Amazona parrots was found for four of the six independently derived genome rearrangements, and a previously undescribed gene order was found in Prioniturus luconensis, representing a fifth clade with rearranged genomes; the gene order resulting from the remaining rearrangement event could not be confirmed. In all rearranged genomes, two copies of the control region are present and are very similar at the sequence level, while duplicates of the other genes involved in the rearrangement show signs of degeneration or have been lost altogether. We compared rates of sequence evolution in genomes with and without control region duplications and did not find a consistent acceleration or deceleration associated with the duplications. This could be due to the fact that most of the genome rearrangement events in parrots are ancient, and additionally, to an effect of body size on evolutionary rate that we found for mitochondrial but not nuclear sequences. Base composition analyses found that relative to other birds, parrots have unusually strong compositional asymmetry (AT- and GC-skew) in their coding sequences, especially at fourfold degenerate sites. Furthermore, we found higher AT skew in species with control region duplications. One

  14. Structure of the Escherichia coli Antitoxin MqsA (YgiT/b3021) Bound to Its Gene Promoter Reveals Extensive Domain Rearrangements and the Specificity of Transcriptional Regulation

    Energy Technology Data Exchange (ETDEWEB)

    B Brown; T Wood; W Peti; R Page

    2011-12-31

    Bacterial cultures, especially biofilms, produce a small number of persister cells, a genetically identical subpopulation of wild type cells that are metabolically dormant, exhibit multidrug tolerance, and are highly enriched in bacterial toxins. The gene most highly up-regulated in Escherichia coli persisters is mqsR, a ribonuclease toxin that, along with mqsA, forms a novel toxin-antitoxin (TA) system. Like all known TA systems, both the MqsR-MqsA complex and MqsA alone regulate their own transcription. Despite the importance of TA systems in persistence and biofilms, very little is known about how TA modules, and antitoxins in particular, bind and recognize DNA at a molecular level. Here, we report the crystal structure of MqsA bound to a 26-bp fragment from the mqsRA promoter. We show that MqsA binds DNA predominantly via its C-terminal helix-turn-helix domain, with direct binding of recognition helix residues Asn{sup 97} and Arg{sup 010} to the DNA major groove. Unexpectedly, the structure also revealed that the MqsA N-terminal domain interacts with the DNA phosphate backbone. This results in a more than 105{sup o} rotation of the N-terminal domains between the free and complexed states, an unprecedented rearrangement for an antitoxin. The structure also shows that MqsA bends the DNA by more than 55{sup o} in order to achieve symmetrical binding. Finally, using a combination of biochemical and NMR studies, we show that the DNA sequence specificity of MqsA is mediated by direct readout.

  15. IgH/TCR基因重排与EB病毒原位杂交联合分析在淋巴瘤诊断中的应用%The application of conjoint analysis of IgH/TCR gene rearrangements and EB virus in situ hybridization in diagnosis of lymphoma

    Institute of Scientific and Technical Information of China (English)

    周薇; 黎刚; 修芸

    2014-01-01

    目的:探讨免疫球蛋白重链/T细胞受体(IgH/TCR)基因重排检测联合EB病毒(EBV)原位杂交在淋巴瘤诊断中的应用,分析EBV+-B细胞淋巴瘤的细胞学及基因组学特征、鉴别诊断要点,以缩短诊断时间,减少误诊。方法采用IgH/TCR基因重排与EB原位杂交联合分析诊断EBV+-B细胞淋巴瘤1例,分析其免疫组化特征、EBV原位杂交、基因重排结果。结果 EBV+-B细胞淋巴瘤临床上主要表现为淋巴结增大,常伴骨髓和外周血浸润。淋巴结活检显示其结构破坏,淋巴滤泡减少,淋巴结高度增生性病变,可见轻至中度异型淋巴细胞,淋巴窦扩张,组织细胞增生。免疫组化证实EBV感染的细胞毒性B细胞构成病变主体;EBV原位杂交显示部分淋巴细胞核阳性;基因重排提示IgH、免疫球蛋白轻链(Igκ)基因发生克隆性重排,TCRγ无克隆性重排。结论 EBV+-B细胞淋巴瘤从形态学上难以与伯基特淋巴瘤、慢性淋巴细胞白血病等淋巴瘤区分,早期诊断困难。联合应用IgH/TCR基因重排与EBV原位杂交技术对EBV+-B细胞淋巴瘤的诊断有较高准确性。%Objective To investigate the application of immunoglobulin heavy chain/T cell receptor (IgH/TCR) gene re-arrangement and epstein-barr virus(EBV) in situ hybridization in diagnosing lymphoma,analyzing cytological feature and genomic features of EBV+-B cell lymphoma and discriminating the points of diagnosis ,in order to shorten the diagnostic time and avoid misdiagnosis. Methods A total of 1 case with diagnosis of EBV+-B cell lymphoma by IgH/TCR gene rearrangements combined with EB in situ hybridization analysis was performed to analyze its immunohistochemical characteristics ,EBV situ hybridization and results of gene rearrangement. Results The major clinical manifestation of EBV+-B cell lymphoma was lymphadenopathy , which often accompanied by infiltration of the bone marrow and peripheral

  16. The potential of clofarabine in MLL-rearranged infant acute lymphoblastic leukaemia.

    Science.gov (United States)

    Stumpel, Dominique J P M; Schneider, Pauline; Pieters, Rob; Stam, Ronald W

    2015-09-01

    MLL-rearranged acute lymphoblastic leukaemia (ALL) in infants is the most difficult-to-treat type of childhood ALL, displaying a chemotherapy-resistant phenotype, and unique histone modifications, gene expression signatures and DNA methylation patterns. MLL-rearranged infant ALL responds remarkably well to nucleoside analogue drugs in vitro, such as cytarabine and cladribine, and to the demethylating agents decitabine and zebularine as measured by cytotoxicity assays. These observations led to the inclusion of cytarabine into the treatment regimens currently used for infants with ALL. However, survival chances for infants with MLL-rearranged ALL do still not exceed 30-40%. Here we explored the in vitro potential of the novel nucleoside analogue clofarabine for MLL-rearranged infant ALL. Therefore we used both cell line models as well as primary patient cells. Compared with other nucleoside analogues, clofarabine effectively targeted primary MLL-rearranged infant ALL cells at the lowest concentrations, with median LC50 values of ∼25 nM. Interestingly, clofarabine displayed synergistic cytotoxic effects in combination with cytarabine. Furthermore, at concentrations of 5-10nM clofarabine induced demethylation of the promoter region of the tumour suppressor gene FHIT (Fragile Histidine Triad), a gene typically hypermethylated in MLL-rearranged ALL. Demethylation of the FHIT promoter region was accompanied by subtle re-expression of this gene both at the mRNA and protein level. We conclude that clofarabine is an interesting candidate for further studies in MLL-rearranged ALL in infants. PMID:26188848

  17. Detection and Tracking of NY-ESO-1-Specific CD8+ T Cells by High-Throughput T Cell Receptor β (TCRB Gene Rearrangements Sequencing in a Peptide-Vaccinated Patient.

    Directory of Open Access Journals (Sweden)

    Manami Miyai

    Full Text Available Comprehensive immunological evaluation is crucial for monitoring patients undergoing antigen-specific cancer immunotherapy. The identification and quantification of T cell responses is most important for the further development of such therapies. Using well-characterized clinical samples from a high responder patient (TK-f01 in an NY-ESO-1f peptide vaccine study, we performed high-throughput T cell receptor β-chain (TCRB gene next generation sequencing (NGS to monitor the frequency of NY-ESO-1-specific CD8+ T cells. We compared these results with those of conventional immunological assays, such as IFN-γ capture, tetramer binding and limiting dilution clonality assays. We sequenced human TCRB complementarity-determining region 3 (CDR3 rearrangements of two NY-ESO-1f-specific CD8+ T cell clones, 6-8L and 2F6, as well as PBMCs over the course of peptide vaccination. Clone 6-8L possessed the TCRB CDR3 gene TCRBV11-03*01 and BJ02-01*01 with amino acid sequence CASSLRGNEQFF, whereas 2F6 possessed TCRBV05-08*01 and BJ02-04*01 (CASSLVGTNIQYF. Using these two sequences as models, we evaluated the frequency of NY-ESO-1-specific CD8+ T cells in PBMCs ex vivo. The 6-8L CDR3 sequence was the second most frequent in PBMC and was present at high frequency (0.7133% even prior to vaccination, and sustained over the course of vaccination. Despite a marked expansion of NY-ESO-1-specific CD8+ T cells detected from the first through 6th vaccination by tetramer staining and IFN-γ capture assays, as evaluated by CDR3 sequencing the frequency did not increase with increasing rounds of peptide vaccination. By clonal analysis using 12 day in vitro stimulation, the frequency of B*52:01-restricted NY-ESO-1f peptide-specific CD8+ T cells in PBMCs was estimated as only 0.0023%, far below the 0.7133% by NGS sequencing. Thus, assays requiring in vitro stimulation might be underestimating the frequency of clones with lower proliferation potential. High-throughput TCRB

  18. Detection and Tracking of NY-ESO-1-Specific CD8+ T Cells by High-Throughput T Cell Receptor β (TCRB) Gene Rearrangements Sequencing in a Peptide-Vaccinated Patient.

    Science.gov (United States)

    Miyai, Manami; Eikawa, Shingo; Hosoi, Akihiro; Iino, Tamaki; Matsushita, Hirokazu; Isobe, Midori; Uenaka, Akiko; Udono, Heiichiro; Nakajima, Jun; Nakayama, Eiichi; Kakimi, Kazuhiro

    2015-01-01

    Comprehensive immunological evaluation is crucial for monitoring patients undergoing antigen-specific cancer immunotherapy. The identification and quantification of T cell responses is most important for the further development of such therapies. Using well-characterized clinical samples from a high responder patient (TK-f01) in an NY-ESO-1f peptide vaccine study, we performed high-throughput T cell receptor β-chain (TCRB) gene next generation sequencing (NGS) to monitor the frequency of NY-ESO-1-specific CD8+ T cells. We compared these results with those of conventional immunological assays, such as IFN-γ capture, tetramer binding and limiting dilution clonality assays. We sequenced human TCRB complementarity-determining region 3 (CDR3) rearrangements of two NY-ESO-1f-specific CD8+ T cell clones, 6-8L and 2F6, as well as PBMCs over the course of peptide vaccination. Clone 6-8L possessed the TCRB CDR3 gene TCRBV11-03*01 and BJ02-01*01 with amino acid sequence CASSLRGNEQFF, whereas 2F6 possessed TCRBV05-08*01 and BJ02-04*01 (CASSLVGTNIQYF). Using these two sequences as models, we evaluated the frequency of NY-ESO-1-specific CD8+ T cells in PBMCs ex vivo. The 6-8L CDR3 sequence was the second most frequent in PBMC and was present at high frequency (0.7133%) even prior to vaccination, and sustained over the course of vaccination. Despite a marked expansion of NY-ESO-1-specific CD8+ T cells detected from the first through 6th vaccination by tetramer staining and IFN-γ capture assays, as evaluated by CDR3 sequencing the frequency did not increase with increasing rounds of peptide vaccination. By clonal analysis using 12 day in vitro stimulation, the frequency of B*52:01-restricted NY-ESO-1f peptide-specific CD8+ T cells in PBMCs was estimated as only 0.0023%, far below the 0.7133% by NGS sequencing. Thus, assays requiring in vitro stimulation might be underestimating the frequency of clones with lower proliferation potential. High-throughput TCRB sequencing using NGS

  19. Characteristics of T-cell receptor beta gene rearrangement and its role in the detection of minimal residual disease in childhood T-cell acute lymphoblastic leukemia%儿童急性T淋巴细胞白血病T细胞受体β链基因重排的特点及其在微小残留病定量检测中的意义

    Institute of Scientific and Technical Information of China (English)

    刘婕好; 李志刚; 高超; 崔蕾; 吴敏媛

    2008-01-01

    Objective To explore the characteristics of T-cell receptor beta (TCRβ) gene rearrangement in children with T-cell acute lymphoblastic leukemia (T-ALL) and establish a system for quantitative detection of minimal residual disease (MRD) by real-time quantitative PCR (RQ-PCR) targeting the TCRβ gene rearrangement. Methods Multiplex PCR designed by the BIOMED-2 was used to detect TCRβ gene rearrangement in the bone marrow samples of 26 children with T-ALL. Sequences of junctional region were then compared and analyzed in IMGT database. Allele specific oligonucleotide (ASO) upstream primers were designed complementary to the V-D-J or D-J junctional region of TCRβ gene rearrangements. Samples at diagnosis were serially diluted in DNA obtained from mononuclear cells (MNC) from a pool of 20 healthy donors to generate the patient-specific standard curves. Subsequently, TCRβ RQ-PCR was applied to six patients to quantify MRD with germline Jβ primer/probe combinations. To determine the quantity and quality of DNA, we also used RQ-PCR for the N-ras gene.Results Clonal rearrangements were identified in 92.3% of the children with T-ALL ( Vβ-Dβ-Jβ rearrangements in 84.6% and Dβ-Jβ rearrangements in 50% ). Comparative sequence analysis of 42 TCRβ recombination revealed that two downstream Vβ families (BV5, BV6) were preferentially used. The segment Jβ2. 7 was dominant in childhood T-ALL. Jβ1. 3, Jβ2.4, and Jβ2.6 were not detected. The slope of the standard curves was from - 3.54 to -3.37 with the intercepts between 19.35 and 20.51. The correlation coefficients of all the 6 standard curves were ≥0.98. None of the cases had a quantitative range of RQ-PCR lower than 10. During the follow-up, an increased incidence of MRD was found before relapse. Conclusions RQ-PCR, which is a highly sensitive and specific method for detection of TCRβ gene rearrangements, will be of high value to study MRD in T-ALL. Close monitoring of MRD is of great importance for prognosis and

  20. Telomerase activation by genomic rearrangements in high-risk neuroblastoma.

    Science.gov (United States)

    Peifer, Martin; Hertwig, Falk; Roels, Frederik; Dreidax, Daniel; Gartlgruber, Moritz; Menon, Roopika; Krämer, Andrea; Roncaioli, Justin L; Sand, Frederik; Heuckmann, Johannes M; Ikram, Fakhera; Schmidt, Rene; Ackermann, Sandra; Engesser, Anne; Kahlert, Yvonne; Vogel, Wenzel; Altmüller, Janine; Nürnberg, Peter; Thierry-Mieg, Jean; Thierry-Mieg, Danielle; Mariappan, Aruljothi; Heynck, Stefanie; Mariotti, Erika; Henrich, Kai-Oliver; Gloeckner, Christian; Bosco, Graziella; Leuschner, Ivo; Schweiger, Michal R; Savelyeva, Larissa; Watkins, Simon C; Shao, Chunxuan; Bell, Emma; Höfer, Thomas; Achter, Viktor; Lang, Ulrich; Theissen, Jessica; Volland, Ruth; Saadati, Maral; Eggert, Angelika; de Wilde, Bram; Berthold, Frank; Peng, Zhiyu; Zhao, Chen; Shi, Leming; Ortmann, Monika; Büttner, Reinhard; Perner, Sven; Hero, Barbara; Schramm, Alexander; Schulte, Johannes H; Herrmann, Carl; O'Sullivan, Roderick J; Westermann, Frank; Thomas, Roman K; Fischer, Matthias

    2015-10-29

    Neuroblastoma is a malignant paediatric tumour of the sympathetic nervous system. Roughly half of these tumours regress spontaneously or are cured by limited therapy. By contrast, high-risk neuroblastomas have an unfavourable clinical course despite intensive multimodal treatment, and their molecular basis has remained largely elusive. Here we have performed whole-genome sequencing of 56 neuroblastomas (high-risk, n = 39; low-risk, n = 17) and discovered recurrent genomic rearrangements affecting a chromosomal region at 5p15.33 proximal of the telomerase reverse transcriptase gene (TERT). These rearrangements occurred only in high-risk neuroblastomas (12/39, 31%) in a mutually exclusive fashion with MYCN amplifications and ATRX mutations, which are known genetic events in this tumour type. In an extended case series (n = 217), TERT rearrangements defined a subgroup of high-risk tumours with particularly poor outcome. Despite a large structural diversity of these rearrangements, they all induced massive transcriptional upregulation of TERT. In the remaining high-risk tumours, TERT expression was also elevated in MYCN-amplified tumours, whereas alternative lengthening of telomeres was present in neuroblastomas without TERT or MYCN alterations, suggesting that telomere lengthening represents a central mechanism defining this subtype. The 5p15.33 rearrangements juxtapose the TERT coding sequence to strong enhancer elements, resulting in massive chromatin remodelling and DNA methylation of the affected region. Supporting a functional role of TERT, neuroblastoma cell lines bearing rearrangements or amplified MYCN exhibited both upregulated TERT expression and enzymatic telomerase activity. In summary, our findings show that remodelling of the genomic context abrogates transcriptional silencing of TERT in high-risk neuroblastoma and places telomerase activation in the centre of transformation in a large fraction of these tumours.

  1. Telomerase activation by genomic rearrangements in high-risk neuroblastoma.

    Science.gov (United States)

    Peifer, Martin; Hertwig, Falk; Roels, Frederik; Dreidax, Daniel; Gartlgruber, Moritz; Menon, Roopika; Krämer, Andrea; Roncaioli, Justin L; Sand, Frederik; Heuckmann, Johannes M; Ikram, Fakhera; Schmidt, Rene; Ackermann, Sandra; Engesser, Anne; Kahlert, Yvonne; Vogel, Wenzel; Altmüller, Janine; Nürnberg, Peter; Thierry-Mieg, Jean; Thierry-Mieg, Danielle; Mariappan, Aruljothi; Heynck, Stefanie; Mariotti, Erika; Henrich, Kai-Oliver; Gloeckner, Christian; Bosco, Graziella; Leuschner, Ivo; Schweiger, Michal R; Savelyeva, Larissa; Watkins, Simon C; Shao, Chunxuan; Bell, Emma; Höfer, Thomas; Achter, Viktor; Lang, Ulrich; Theissen, Jessica; Volland, Ruth; Saadati, Maral; Eggert, Angelika; de Wilde, Bram; Berthold, Frank; Peng, Zhiyu; Zhao, Chen; Shi, Leming; Ortmann, Monika; Büttner, Reinhard; Perner, Sven; Hero, Barbara; Schramm, Alexander; Schulte, Johannes H; Herrmann, Carl; O'Sullivan, Roderick J; Westermann, Frank; Thomas, Roman K; Fischer, Matthias

    2015-10-29

    Neuroblastoma is a malignant paediatric tumour of the sympathetic nervous system. Roughly half of these tumours regress spontaneously or are cured by limited therapy. By contrast, high-risk neuroblastomas have an unfavourable clinical course despite intensive multimodal treatment, and their molecular basis has remained largely elusive. Here we have performed whole-genome sequencing of 56 neuroblastomas (high-risk, n = 39; low-risk, n = 17) and discovered recurrent genomic rearrangements affecting a chromosomal region at 5p15.33 proximal of the telomerase reverse transcriptase gene (TERT). These rearrangements occurred only in high-risk neuroblastomas (12/39, 31%) in a mutually exclusive fashion with MYCN amplifications and ATRX mutations, which are known genetic events in this tumour type. In an extended case series (n = 217), TERT rearrangements defined a subgroup of high-risk tumours with particularly poor outcome. Despite a large structural diversity of these rearrangements, they all induced massive transcriptional upregulation of TERT. In the remaining high-risk tumours, TERT expression was also elevated in MYCN-amplified tumours, whereas alternative lengthening of telomeres was present in neuroblastomas without TERT or MYCN alterations, suggesting that telomere lengthening represents a central mechanism defining this subtype. The 5p15.33 rearrangements juxtapose the TERT coding sequence to strong enhancer elements, resulting in massive chromatin remodelling and DNA methylation of the affected region. Supporting a functional role of TERT, neuroblastoma cell lines bearing rearrangements or amplified MYCN exhibited both upregulated TERT expression and enzymatic telomerase activity. In summary, our findings show that remodelling of the genomic context abrogates transcriptional silencing of TERT in high-risk neuroblastoma and places telomerase activation in the centre of transformation in a large fraction of these tumours. PMID:26466568

  2. Clinical characteristics and prognosis of concurrent positive t(14;18) and myc gene rearrangement ;in diffuse large B cell lymphoma%t(14;18)和 myc 基因重排双阳性弥漫性大 B 细胞淋巴瘤的临床特征和预后

    Institute of Scientific and Technical Information of China (English)

    张宏伟; 白敏; 苏丽萍; 陈振文; 王列样; 贺建霞; 郑玉萍; 韩维娥; 杨斌; 王艳丽; 赵志强

    2016-01-01

    Objective To study the incidence of positive t(14;18) and myc gene rearrangement, and the clinical features and prognosis of concurrent positive t ( 14;18 ) and myc gene rearrangement“ double-hit lymphoma” (DHL) in diffuse large B cell lymphoma.Me thods The positive t(14;18) and myc gene rearrangement in 106 cases of DLBCL were analyzed using interphase fluorescent in situ hybridization ( FISH ) technique. The expression of myc and bcl-2 proteins was determined by immunohistochemistry.The relationship of positive t ( 14;18) and myc gene rearrangement with clinical features, pathogenesis and prognosis for the patients was analyzed.SPSS 16.0 software was used for statistical analysis.Results Among the 106 cases, there were 27 (25.5%) cases with positive t(14;18) and 13 (12.3%) cases with myc gene rearrangement, and 7 cases (6.6%) of DLBCL with concurrent t(14; 18)-positive and myc gene rearrangement.A relationship was observed between positive t ( 14;18 ) and myc gene rearrangement ( P=0.019) .The follow-up data showed that the 7 DHL patients were in age of 528-4 years, the International Prognostic Index (IPI) scores were 3 in two cases, 4 in four cases and 5 in one case, and the ECOG scores were 3 in all the7 cases .Four patients had bone marrow involvement and were combined with leukemia.The survival time ranged from 0.5 to 6 months, with a median survival of 4 months.The univariate analysis showed that B symptom, Ann Arbor stage, ECOG score, LDH level, IPI score, immunophenotype, bcl-2 protein expression, myc protein expression,and myc gene rearrangement were all associated with poor prognosis ( P<0.05 for all) .The multivariate analysis using a COX proportional hazard model confirmed that ECOG score, bcl-2 protein expression, myc protein expression , myc gene rearrangement, and immunophenotype were independent prognostic factors affecting survival ( P<0.05 for all) , among them, the myc gene rearrangement was the strongest prognostic factor ( OR=4.337,P<0

  3. Sequence features contributing to chromosomal rearrangements in Neisseria gonorrhoeae.

    Directory of Open Access Journals (Sweden)

    Russell Spencer-Smith

    Full Text Available Through whole genome sequence alignments, breakpoints in chromosomal synteny can be identified and the sequence features associated with these determined. Alignments of the genome sequences of Neisseria gonorrhoeae strain FA1090, N.gonorrhoeae strain NCCP11945, and N. gonorrhoeae strain TCDC-NG08107 reveal chromosomal rearrangements that have occurred. Based on these alignments and dot plot pair-wise comparisons, the overall chromosomal arrangement of strain NCCP11945 and TCDC-NG08107 are very similar, with no large inversions or translocations. The insertion of the Gonococcal Genetic Island in strain NCCP11945 is the most prominent distinguishing feature differentiating these strains. When strain NCCP11945 is compared to strain FA1090, however, 14 breakpoints in chromosomal synteny are identified between these gonococcal strains. The majority of these, 11 of 14, are associated with a prophage, IS elements, or IS-like repeat enclosed elements which appear to have played a role in the rearrangements observed. Additional rearrangements of small regions of the genome are associated with pilin genes. Evidence presented here suggests that the rearrangements of blocks of sequence are mediated by activation of prophage and associated IS elements and reintegration elsewhere in the genome or by homologous recombination between IS-like elements that have generated inversions.

  4. Highly variable rates of genome rearrangements between hemiascomycetous yeast lineages.

    Directory of Open Access Journals (Sweden)

    2006-03-01

    Full Text Available Hemiascomycete yeasts cover an evolutionary span comparable to that of the entire phylum of chordates. Since this group currently contains the largest number of complete genome sequences it presents unique opportunities to understand the evolution of genome organization in eukaryotes. We inferred rates of genome instability on all branches of a phylogenetic tree for 11 species and calculated species-specific rates of genome rearrangements. We characterized all inversion events that occurred within synteny blocks between six representatives of the different lineages. We show that the rates of macro- and microrearrangements of gene order are correlated within individual lineages but are highly variable across different lineages. The most unstable genomes correspond to the pathogenic yeasts Candida albicans and Candida glabrata. Chromosomal maps have been intensively shuffled by numerous interchromosomal rearrangements, even between species that have retained a very high physical fraction of their genomes within small synteny blocks. Despite this intensive reshuffling of gene positions, essential genes, which cluster in low recombination regions in the genome of Saccharomyces cerevisiae, tend to remain syntenic during evolution. This work reveals that the high plasticity of eukaryotic genomes results from rearrangement rates that vary between lineages but also at different evolutionary times of a given lineage.

  5. 伴11q23/MLL基因重排急性淋巴细胞白血病短期内广泛髓外、髓内复发1例并文献复习%Short-term extensive extramedullary and intramedullary relapse of acute lymphoblastic leukemia with 11q23/MLL gene rearrangement : a case report and literature review

    Institute of Scientific and Technical Information of China (English)

    韩乔燕; 孙淼; 吴玲玉

    2013-01-01

    A case of short-term extensive extramedullary and intramedullary relapse of acute lymphoblastic leukemia with 11q23/MLL gene rearrangement was reported and related literature were reviewed.Clinical manifestations,laboratory findings,diagnosis and treatment of the patient were analyzed.The patient had acute onset,rapid progression,short survival and poor results after multiple chemotherapy.MLL-related leukemia is a disease with complicated clinical manifestations.Early diagnosis,timely development of a more reasonable and individual program is the key to improve the prognosis.

  6. TPR-MET oncogenic rearrangement: detection by polymerase chain reaction amplification of the transcript and expression in human tumor cell lines.

    OpenAIRE

    Soman, N R; Wogan, G N; Rhim, J S

    1990-01-01

    Activation of the MET protooncogene by a rearrangement involving the fusion of TPR and MET specific gene sequences has been observed in a human osteosarcoma cell line (HOS) treated in vitro with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). No information has been available about the possible occurrence of this rearrangement in human tumors. To facilitate rapid screening of human cell lines and tumor samples for this specific gene rearrangement, we developed a sensitive detection method based ...

  7. Rearrangements of organic peroxides and related processes

    Science.gov (United States)

    Yaremenko, Ivan A; Vil’, Vera A; Demchuk, Dmitry V

    2016-01-01

    Summary This review is the first to collate and summarize main data on named and unnamed rearrangement reactions of peroxides. It should be noted, that in the chemistry of peroxides two types of processes are considered under the term rearrangements. These are conventional rearrangements occurring with the retention of the molecular weight and transformations of one of the peroxide moieties after O–O-bond cleavage. Detailed information about the Baeyer−Villiger, Criegee, Hock, Kornblum−DeLaMare, Dakin, Elbs, Schenck, Smith, Wieland, and Story reactions is given. Unnamed rearrangements of organic peroxides and related processes are also analyzed. The rearrangements and related processes of important natural and synthetic peroxides are discussed separately. PMID:27559418

  8. Mouse Model for ROS1-Rearranged Lung Cancer

    OpenAIRE

    Yasuhito Arai; Yasushi Totoki; Hiroyuki Takahashi; Hiromi Nakamura; Natsuko Hama; Takashi Kohno; Koji Tsuta; Akihiko Yoshida; Hisao Asamura; Michihiro Mutoh; Fumie Hosoda; Hitoshi Tsuda; Tatsuhiro Shibata

    2013-01-01

    Genetic rearrangement of the ROS1 receptor tyrosine kinase was recently identified as a distinct molecular signature for human non-small cell lung cancer (NSCLC). However, direct evidence of lung carcinogenesis induced by ROS1 fusion genes remains to be verified. The present study shows that EZR-ROS1 plays an essential role in the oncogenesis of NSCLC harboring the fusion gene. EZR-ROS1 was identified in four female patients of lung adenocarcinoma. Three of them were never smokers. Interstiti...

  9. Immunoglobulin genes

    Energy Technology Data Exchange (ETDEWEB)

    Honjo, T. (Kyoto Univ. (Japan)); Alt, F.W. (Columbia Univ., Dobbs Ferry, NY (USA). Hudson Labs.); Rabbitts, T.H. (Medical Research Council, Cambridge (UK))

    1989-01-01

    This book reports on the structure, function, and expression of the genes encoding antibodies in normal and neoplastic cells. Topics covered are: B Cells; Organization and rearrangement of immunoglobin genes; Immunoglobin genes in disease; Immunoglobin gene expression; and Immunoglobin-related genes.

  10. Genome rearrangement affects RNA virus adaptability on prostate cancer cells

    Directory of Open Access Journals (Sweden)

    Kendra ePesko

    2015-04-01

    Full Text Available Gene order is often highly conserved within taxonomic groups, such that organisms with rearranged genomes tend to be less fit than wildtype gene orders, and suggesting natural selection favors genome architectures that maximize fitness. But it is unclear whether rearranged genomes hinder adaptability: capacity to evolutionarily improve in a new environment. Negative-sense nonsegmented RNA viruses (order Mononegavirales have specific genome architecture: 3′ UTR – core protein genes – envelope protein genes – RNA-dependent RNA-polymerase gene – 5′ UTR. To test how genome architecture affects RNA virus evolution, we examined vesicular stomatitis virus (VSV variants with the nucleocapsid (N gene moved sequentially downstream in the genome. Because RNA polymerase stuttering in VSV replication causes greater mRNA production in upstream genes, N-gene translocation towards the 5’ end leads to stepwise decreases in N transcription, viral replication and progeny production, and also impacts the activation of type 1 interferon mediated antiviral responses. We evolved VSV gene-order variants in two prostate cancer cell lines: LNCap cells deficient in innate immune response to viral infection, and PC3 cells that mount an IFN stimulated anti-viral response to infection. We observed that gene order affects phenotypic adaptability (reproductive growth; viral suppression of immune function, especially on PC3 cells that strongly select against virus infection. Overall, populations derived from the least-fit ancestor (most-altered N position architecture adapted fastest, consistent with theory predicting populations with low initial fitness should improve faster in evolutionary time. Also, we observed correlated responses to selection, where viruses improved across both hosts, rather than suffer fitness trade-offs on unselected hosts. Whole genomics revealed multiple mutations in evolved variants, some of which were conserved across selective

  11. Influence of genetic background on the occurrence of chromosomal rearrangements in Saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    Potier Serge

    2009-03-01

    Full Text Available Abstract Background Chromosomal rearrangements such as duplications and deletions are key factors in evolutionary processes because they promote genomic plasticity. Although the genetic variations in the Saccharomyces cerevisiae species have been well documented, there is little known to date about the impact of the genetic background on the appearance of rearrangements. Results Using the same genetic screening, the type of rearrangements and the mutation rates observed in the S288c S. cerevisiae strain were compared to previous findings obtained in the FL100 background. Transposon-associated rearrangements, a major chromosomal rearrangement event selected in FL100, were not detected in S288c. The mechanisms involved in the occurrence of deletions and duplications in the S288c strain were also tackled, using strains deleted for genes implicated in homologous recombination (HR or non-homologous end joining (NHEJ. Our results indicate that an Yku80p-independent NHEJ pathway is involved in the occurrence of these rearrangements in the S288c background. Conclusion The comparison of two different S. cerevisiae strains, FL100 and S288c, allowed us to conclude that intra-species genomic variations have an important impact on the occurrence of chromosomal rearrangement and that this variability can partly be explained by differences in Ty1 retrotransposon activity.

  12. Application of BIOMED-2 primers in immunoglobulin gene rearrangement analysis of ocular adnexal lymphoma:a pilot study%应用BIOMED-2引物检测眼附属器淋巴瘤Ig基因重排的初步研究

    Institute of Scientific and Technical Information of China (English)

    王玉川; 王犁明; 郝朋; 应铭; 韩瑞芳; 林锦镛

    2010-01-01

    Objective To assess the practical value of BIOMED-2 primers in the diagnosis of ocular adnexal lymphoma by PCR. Methods DNA was extracted from 63 formalin-fixed paraffin-embedded (FFPE) ocular adnexal lymphoma specimens. The DNA quality was evaluated by PCR-based amplification of housekeeping gene β-actin. IgH_B and IgK_B primers of BIOMED-2 standardized clonality analysis system were used to evaluate the immunoglobin gene rearrangements. PCR products were analyzed using capillary electrophoresis and GeneScan software. Results 76.2% (48/63) of FFPE samples produced amplifiable DNA for detection of Ig gene rearrangements. Positive detection rates by BIOMED-2 IgH_B and IgK_B primers were 79. 2% (38/48) and 68. 8% (33/48) , respectively, with a combined positive detection rate of 91. 7% (44/48). Conclusions IgH_B and IgK_R primers of BIOMED-2 are suitable for the detection of clonal rearrangements of Ig gene using FFPE specimens of ocular adnexal lymphomas.%目的 初步评价BIOMED-2引物在辅助诊断眼附属器淋巴瘤的应用价值.方法 收集63例眼附属器淋巴瘤,均为甲醛固定的石蜡包埋标本,提取基因组DNA并通过扩增管家基因β-actin检测其质量,应用BIOMED-2标准化基因重排检测系统中IgH_B和IgK_B两套多重PCR引物进行Ig基因的PCR扩增,并利用基因扫描技术对扩增产物进行克隆性分析.结果 76.2%(48/63)淋巴瘤石蜡包埋标本的DNA可扩增出300 bp大小的β-actin,适于基因重排检测.IgH_B和IgK_B多重PCR引物的淋巴瘤检出率分别为79.2%(38/48)和68.8%(33/48),二者联合的检出率为91.7%(44/48).结论 应用较少的BIOMED-2引物结合基因扫描技术能检测出大多数眼附属器淋巴瘤,对临床病理诊断具有较高的辅助价值.

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

    Science.gov (United States)

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

    2015-01-01

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

  14. Interphase FISH detection of BCL2 rearrangement in follicular lymphoma using breakpoint-flanking probes

    NARCIS (Netherlands)

    Vaandrager, J W; Schuuring, E; Raap, T; Philippo, K; Kleiverda, K; Kluin, P

    2000-01-01

    Rearrangement of the BCL2 gene is an important parameter for the differential diagnosis of non-Hodgkin lymphomas. Although a relatively large proportion of breakpoints is clustered, many are missed by standard PCR. A FISH assay is therefore desired. Up to now, a lack of probes flanking the BCL2 gene

  15. Immunohistochemical detection of ROS1 is useful for identifying ROS1 rearrangements in lung cancers.

    Science.gov (United States)

    Yoshida, Akihiko; Tsuta, Koji; Wakai, Susumu; Arai, Yasuhito; Asamura, Hisao; Shibata, Tatsuhiro; Furuta, Koh; Kohno, Takashi; Kushima, Ryoji

    2014-05-01

    The recent discovery and characterization of an oncogenic ROS1 gene fusion in a subset of lung cancers has raised significant clinical interest because small molecule inhibitors may be effective to these tumors. As lung cancers with ROS1 rearrangements comprise only 1-3% of lung adenocarcinomas, patients with such tumors must be identified to gain optimal benefit from molecular therapy. Recently, immunohistochemical analyses using a novel anti-ROS1 rabbit monoclonal antibody (D4D6) have shown promise for accurate identification of ROS1-rearranged cancers. To validate this finding, we compared the immunostaining results of tissue microarrays (TMAs) containing 17 ROS1-rearranged and 253 ROS1-non-rearranged lung carcinomas. All 17 ROS1-rearranged cancers showed ROS1 immunoreactivity mostly in a diffuse and moderate-to-strong manner with an H-score range of 5-300 (median, 260). In contrast, 69% of ROS1-non-rearranged cancers lacked detectable immunoreactivity, whereas the remaining 31% showed reactivity mainly in a weak or focal manner. The H-score for the entire ROS1-non-rearranged group ranged from 0 to 240 (median, 0). The difference in H-score between the two cohorts was statistically significant, and the H-score cutoff (≥150) allowed optimal discrimination (94% sensitivity and 98% specificity). Similar but slightly less-specific performance was achieved using the extent of diffuse (≥75%) staining or ≥2+ staining intensity as cutoffs. CD74-ROS1 and EZR-ROS1 fusions were significantly associated with at least focal globular immunoreactivity and plasma membranous accentuation, respectively, and these patterns were specific to ROS1-rearranged cases. Although full-length ROS1 is expressed in some ROS1-non-rearranged cases, we showed that establishment of an optimal set of interpretative criteria makes ROS1 immunohistochemistry a valuable method to rapidly and accurately screen lung cancer patients for appropriate molecular therapy. PMID:24186139

  16. Delineating Rearrangements in Single Yeast Artificial Chromosomes by Quantitative DNA Fiber Mapping

    Energy Technology Data Exchange (ETDEWEB)

    Weier, Heinz-Ulrich G.; Greulich-Bode, Karin M.; Wu, Jenny; Duell, Thomas

    2009-09-18

    Cloning of large chunks of human genomic DNA in recombinant systems such as yeast or bacterial artificial chromosomes has greatly facilitated the construction of physical maps, the positional cloning of disease genes or the preparation of patient-specific DNA probes for diagnostic purposes. For this process to work efficiently, the DNA cloning process and subsequent clone propagation need to maintain stable inserts that are neither deleted nor otherwise rearranged. Some regions of the human genome; however, appear to have a higher propensity than others to rearrange in any host system. Thus, techniques to detect and accurately characterize such rearrangements need to be developed. We developed a technique termed 'Quantitative DNA Fiber Mapping (QDFM)' that allows accurate tagging of sequence elements of interest with near kilobase accuracy and optimized it for delineation of rearrangements in recombinant DNA clones. This paper demonstrates the power of this microscopic approach by investigating YAC rearrangements. In our examples, high-resolution physical maps for regions within the immunoglobulin lambda variant gene cluster were constructed for three different YAC clones carrying deletions of 95 kb and more. Rearrangements within YACs could be demonstrated unambiguously by pairwise mapping of cosmids along YAC DNA molecules. When coverage by YAC clones was not available, distances between cosmid clones were estimated by hybridization of cosmids onto DNA fibers prepared from human genomic DNA. In addition, the QDFM technology provides essential information about clone stability facilitating closure of the maps of the human genome as well as those of model organisms.

  17. Rearrangement of Legal Holidays Opens Hot Debate

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    @@ On November 9, the National Development and Reform Commission conducted a poll regarding the rearrangement of national legal holidays on its official website.After a year of research and study, a framework for the changes has been completed.

  18. Input-output rearrangement of isolated converters

    DEFF Research Database (Denmark)

    Madsen, Mickey Pierre; Kovacevic, Milovan; Mønster, Jakob Døllner;

    2015-01-01

    This paper presents a new way of rearranging the input and output of isolated converters. The new arrangement posses several advantages, as increased voltage range, higher power handling capabilities, reduced voltage stress and improved efficiency, for applications where galvanic isolation...

  19. BIOMED-2系统引物用于检测T细胞淋巴瘤石蜡样本T细胞受体γ基因重排的研究%Application of BIOMED-2 primers in analysis of T-cell receptor γ gene rearrangements in paraffin-embedded tissue specimens of T-cell lymphoma

    Institute of Scientific and Technical Information of China (English)

    唐源; 江炜; 李雷; 纪洪; 李韵; 李甘地; 刘卫平

    2009-01-01

    目的 了解BIOMED-2系统T细胞受体(TCR)γ引物组合对T细胞淋巴瘤的常规石蜡包埋组织样本中TCR基因重排的检出情况及其实用性.方法 用酚/氯仿法提取55例各种组织类型的T细胞淋巴瘤石蜡包埋组织样本的DNA并通过扩增看家基因β-globin检测其质量,利用BIOMED-2系统TCR-γ引物组合和TCR-γ基因通用型引物(TVG/TJX)对55例进行TCR基因重排检测,比较二者的检出率并进行统计学分析.结果 BIOMED-2系统TCR-γ引物组合和TCRγ基因通用型引物(TVG/TJX)的TCR基因重排检出率分别为76.4%和60.0%,前者高于后者,二者的差异无统计学意义(P>0.05).结论 BIOMED-2系统TCRγ引物组合适用于本组T细胞淋巴瘤石蜡包埋组织样本的TCR基因重排检测.%Objective To evaluate the practical values of PCR detectable T-cell receptor (TCR) gene rearrangement in paraffin embedded tissue samples in the diagnosis of T-cell malignancies using BIOMED-2 PCR multiplex tubes TCRγ(A + B). Methods Traditional phenol-chloroform method was used to extract DNA from 55 cases of archival paraffin embedded tissues samples of T-cell malignancies and the DNA quality was evaluated by PCR-based amplification of housekeeping gone β-globin. The selected BIOMED-2 PCR multiplex tubes TCRγ(A + B) were used to detect TCR gene rearrangement and comparison with the results of universal TCR primers (TVG/TJX) was performed. Results Positive detection rates by the BIOMED-2 multiplex tubes TCRγ(A + B) and the universal primers (TVG/TJX) were 76.4% and 60.0%, respectively. There were not statistical difference between the methods (P > 0.05). Conclusion BIOMED-2 multiplex tubes TCRγ(A + B) is suitable for detection of clonal rearrangements of TCR genes in current archival paraffin embeded tissue samples of T-cell malignancies.

  20. 应用SYBR GreenⅠ实时荧光定量聚合酶链反应检测常染色体隐性遗传早发性帕金森综合征的parkin基因外显子重排突变%Analysis of exon rearrangements in the parkin gene in patients with autosomal recessive early-onset parkinsonism using SYBR Green Ⅰ Real-time PCR

    Institute of Scientific and Technical Information of China (English)

    唐北沙; 严新翔; 聂利珞; 郭纪锋; 张海南; 张学伟; 王磊; 沈璐; 江泓; 夏昆

    2009-01-01

    目的 建立应用SYBR GreenⅠ实时荧光定量聚合酶链反应(Real-time PCR,RT-PCR)检测parkin基因外显子重排突变的技术平台,应用该技术对常染色体隐性遗传早发型帕金森综合征(autosomal recessive early-onset parkinsonism,AREP) 家系进行parkin基因外显子重排突变分析.方法 应用SYBR GreenⅠRT-PCR技术对32个中国AREP家系进行parkin基因外显子重排突变分析.结果 14个家系先证者存在parkin基因外显子重排突变,其中3个为纯合缺失突变、3个为复杂杂合缺失突变和8个杂合缺失突变,未发现外显子重复突变,突变主要累及第2~4号外显子.结论 建立了应用SYBR GreenⅠRT-PCR技术检测parkin基因外显子重排突变的基因检测平台;中国AREP 家系的parkin基因外显子重排突变频率为43.8%,与国外报道相似.%Objective To develop a method of detection exon rearrangements in the parkin gene (PARK2) using SYBR Green Ⅰ real-time PCR and to analyze PARK2 exon rearrangement mutations in families with autosomal recessive early-onset parkinsonism (AREP) using this method. Methods Exon rearrangement in PARK2 was screened by SYBR Green Ⅰ real-time PCR in 32 families with AREP. Results Exon rearrangement mutations were found in 14 families, including 3 compound heterozygous deletions;3 homozygous deletions;and 8 heterozygous deletions. No duplication mutation was found. Hotspot for exon rearrangements clustered in exons 2 through 4. Conclusions We have developed a gene test method using SYBR Green Ⅰ Real-time PCR to detect exon rearrangements in the gene PARK2. The frequency of PARK2 mutation is 43.8% in Chinese families with AREP. This frequency is similar to reported findings in other countries.

  1. Comparative study between primary mediastinal B-cell lymphoma and non-mediastinal diffuse large B-cell lymphoma by immunoglobulin gene rearrangement and Epstein-Barr virus infection detection%原发性纵隔B细胞淋巴瘤与非纵隔弥漫性大B细胞淋巴瘤在基因重排检测与EB病毒感染方面的对比研究

    Institute of Scientific and Technical Information of China (English)

    钟定荣; 凌庆; 师晓华; 梁智勇; 刘彤华

    2012-01-01

    Objective To investigate the differences between primary mediastinal B-cell lymphoma (PMBCL) and non-mediastinal conventional diffuse large B-cell common lymphoma (DLBCL) in immunoglobulin gene rearrangement and EB virus infections.Methods Twenty cases of PMBCL and 30 cases of non-mediastinal DLBCL were collected from September,2000 to May,2011.Pathological data were retrospectively analysed.Immunoglobulin heavy chain and light chain gene rearrangements and EBER in-situ hybridization were performed.Results Six of 20 cases of PMBCL showed monoclonal gene rearrangement,all of which were weakly detected.Twenty-seven of 30 cases of ordinary diffuse large B-cell lymphoma showed monoclonal gene rearrangement,which were strongly detected ( 90.0% ).Only 1 of 20 cases PMBCL and 2 of 30 cases of DLBCL were positive for EBER in-situ hybridization.Conclusions The detection rate of immunoglobulin gene rearrangement is significantly lower in PMBCL than that of non-mediastinal DLBCL.However,EB virus infection rates are very low in both types of lymphomas.%目的 探讨原发性纵隔B细胞淋巴瘤(PMBCL)与非纵隔弥漫性大B细胞淋巴瘤(DLBCL)在基因重排检测与EB病毒感染方面的差异.方法 收集2000年9月至2011年5月北京协和医院手术切除的PMBCL 20例,选取同期非纵隔DLBCL 30例作为对照,进行回顾性病理学分析并进行重链和轻链基因重排检测、EBER原位杂交检测.结果 20例PMBCL中6例基因重排检测呈单克隆性,均为弱阳性条带;30例DLBCL中27例基因重排检测呈单克隆性(90.0%),均为强阳性条带;EBER在20例PMBCL中检测到1例阳性,在30例DLBCL中检测到2例阳性.结论 PMBCL在重链和轻链的基因重排检测方面单克隆率低,而非纵隔DLBCL单克隆率高,二者具有显著差异;但原位杂交检测EBER,二者感染率均低,无明显区别.

  2. Mouse model for ROS1-rearranged lung cancer.

    Directory of Open Access Journals (Sweden)

    Yasuhito Arai

    Full Text Available Genetic rearrangement of the ROS1 receptor tyrosine kinase was recently identified as a distinct molecular signature for human non-small cell lung cancer (NSCLC. However, direct evidence of lung carcinogenesis induced by ROS1 fusion genes remains to be verified. The present study shows that EZR-ROS1 plays an essential role in the oncogenesis of NSCLC harboring the fusion gene. EZR-ROS1 was identified in four female patients of lung adenocarcinoma. Three of them were never smokers. Interstitial deletion of 6q22-q25 resulted in gene fusion. Expression of the fusion kinase in NIH3T3 cells induced anchorage-independent growth in vitro, and subcutaneous tumors in nude mice. This transforming ability was attributable to its kinase activity. The ALK/MET/ROS1 kinase inhibitor, crizotinib, suppressed fusion-induced anchorage-independent growth of NIH3T3 cells. Most importantly, established transgenic mouse lines specifically expressing EZR-ROS1 in lung alveolar epithelial cells developed multiple adenocarcinoma nodules in both lungs at an early age. These data suggest that the EZR-ROS1 is a pivotal oncogene in human NSCLC, and that this animal model could be valuable for exploring therapeutic agents against ROS1-rearranged lung cancer.

  3. Mouse Model for ROS1-Rearranged Lung Cancer

    Science.gov (United States)

    Takahashi, Hiroyuki; Nakamura, Hiromi; Hama, Natsuko; Kohno, Takashi; Tsuta, Koji; Yoshida, Akihiko; Asamura, Hisao; Mutoh, Michihiro; Hosoda, Fumie; Tsuda, Hitoshi; Shibata, Tatsuhiro

    2013-01-01

    Genetic rearrangement of the ROS1 receptor tyrosine kinase was recently identified as a distinct molecular signature for human non-small cell lung cancer (NSCLC). However, direct evidence of lung carcinogenesis induced by ROS1 fusion genes remains to be verified. The present study shows that EZR-ROS1 plays an essential role in the oncogenesis of NSCLC harboring the fusion gene. EZR-ROS1 was identified in four female patients of lung adenocarcinoma. Three of them were never smokers. Interstitial deletion of 6q22–q25 resulted in gene fusion. Expression of the fusion kinase in NIH3T3 cells induced anchorage-independent growth in vitro, and subcutaneous tumors in nude mice. This transforming ability was attributable to its kinase activity. The ALK/MET/ROS1 kinase inhibitor, crizotinib, suppressed fusion-induced anchorage-independent growth of NIH3T3 cells. Most importantly, established transgenic mouse lines specifically expressing EZR-ROS1 in lung alveolar epithelial cells developed multiple adenocarcinoma nodules in both lungs at an early age. These data suggest that the EZR-ROS1 is a pivotal oncogene in human NSCLC, and that this animal model could be valuable for exploring therapeutic agents against ROS1-rearranged lung cancer. PMID:23418494

  4. Insights into structural variations and genome rearrangements in prokaryotic genomes.

    Science.gov (United States)

    Periwal, Vinita; Scaria, Vinod

    2015-01-01

    Structural variations (SVs) are genomic rearrangements that affect fairly large fragments of DNA. Most of the SVs such as inversions, deletions and translocations have been largely studied in context of genetic diseases in eukaryotes. However, recent studies demonstrate that genome rearrangements can also have profound impact on prokaryotic genomes, leading to altered cell phenotype. In contrast to single-nucleotide variations, SVs provide a much deeper insight into organization of bacterial genomes at a much better resolution. SVs can confer change in gene copy number, creation of new genes, altered gene expression and many other functional consequences. High-throughput technologies have now made it possible to explore SVs at a much refined resolution in bacterial genomes. Through this review, we aim to highlight the importance of the less explored field of SVs in prokaryotic genomes and their impact. We also discuss its potential applicability in the emerging fields of synthetic biology and genome engineering where targeted SVs could serve to create sophisticated and accurate genome editing.

  5. Chromosomal Rearrangements as Barriers to Genetic Homogenization between Archaic and Modern Humans.

    Science.gov (United States)

    Rogers, Rebekah L

    2015-12-01

    Chromosomal rearrangements, which shuffle DNA throughout the genome, are an important source of divergence across taxa. Using a paired-end read approach with Illumina sequence data for archaic humans, I identify changes in genome structure that occurred recently in human evolution. Hundreds of rearrangements indicate genomic trafficking between the sex chromosomes and autosomes, raising the possibility of sex-specific changes. Additionally, genes adjacent to genome structure changes in Neanderthals are associated with testis-specific expression, consistent with evolutionary theory that new genes commonly form with expression in the testes. I identify one case of new-gene creation through transposition from the Y chromosome to chromosome 10 that combines the 5'-end of the testis-specific gene Fank1 with previously untranscribed sequence. This new transcript experienced copy number expansion in archaic genomes, indicating rapid genomic change. Among rearrangements identified in Neanderthals, 13% are transposition of selfish genetic elements, whereas 32% appear to be ectopic exchange between repeats. In Denisovan, the pattern is similar but numbers are significantly higher with 18% of rearrangements reflecting transposition and 40% ectopic exchange between distantly related repeats. There is an excess of divergent rearrangements relative to polymorphism in Denisovan, which might result from nonuniform rates of mutation, possibly reflecting a burst of transposable element activity in the lineage that led to Denisovan. Finally, loci containing genome structure changes show diminished rates of introgression from Neanderthals into modern humans, consistent with the hypothesis that rearrangements serve as barriers to gene flow during hybridization. Together, these results suggest that this previously unidentified source of genomic variation has important biological consequences in human evolution. PMID:26399483

  6. 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

  7. Detection of 11q23/MLL gene rearrangement in hematological malignancies with fluorescence in situ hybridization assay%间期荧光原位杂交技术检测恶性血液病的11q23/MLL基因重排

    Institute of Scientific and Technical Information of China (English)

    彭智; 冯文莉; 肖志坚; 周迎春; 刘光平; 刘基铎

    2008-01-01

    目的 分析伴有11q23/MLL基因重排的恶性血液病的细胞遗传学特点,探讨荧光原位杂交技术( FISH)在诊断及鉴定恶性血液病11q23/MLL基因重排中的价值.方法 用间期FISH分析11q23/MLL基因易位细胞的30例恶性血液病患者的核型特征, 用MLL双色分离探针绿色标记在 (5′MLL, 光谱绿) 和 (3′MLL, 光谱桔红).结果 应用常规细胞遗传学及间期FISH分析白血病患者30例,结果显示11q23+/MLL+患者9例(30.0%),11q23-/MLL+患者4例(13.3%),11q23+/MLL-患者2例(6.7%),11q23-/MLL-患者15例,检测到部分病例染色体核型分析与间期FISH方法检测11q23异常与MLL基因重排不一致.结论 FISH在检测11q23/MLL基因重排方面与传统的常规细胞遗传学相比具有检出率高的优势,能更有效、直观地分析恶性血液病的染色体异常,对于恶性血液病的诊断以及异常染色体的检出具有广泛的应用前景.%Objective To analyze the cytogenetical characteristic of 11q23/MLL gene rearrangement in hematological malignancies and to investigate the value of fluorescence in situ hybridization (FISH) assay in the diagnosis and appraisal of 11q23/MLL gene rearrangement.Methods FISH assay was performed to analyze the karyotypic characteristic of 11q23/MLL gene rearranged cells in 30 patients with hematological malignancies. The dual color probe was adopted. 5′MLL was labeled with spectrum green and 3′MLL labeled with spectrum orange.Results The incidence of 11q23+/MLL+ in acute leukemia (AL) patients was 30.0% (10 out of 30 cases) and 11q23-/MLL+ was 13.3% (4 cases) , and 11q23+/MLL- was 6.7% (2 cases) and the karyotype of 15 cases was normal. For some patients, different results were obtained by using conentional cytogenetical analysis and interphased FISH assay for detecting 11q23/MLL gene rearrangements.Conclusion FISH assay has greater advantage over cytogenetical study in the analysis of 11q23/MLL abnormality. It is also a promising tool in

  8. Detection of immunoglobulin gene rearrangements by PCR using BIOMED-2 multiplex protocols in acute lymphoblastic leukemia patients%BIOMED-2引物系统检测急性淋巴细胞白血病患者免疫球蛋白基因重排

    Institute of Scientific and Technical Information of China (English)

    李洁; 徐兵; 宋小燕; 陈国枢; 周淑芸

    2009-01-01

    Objective To investigate the sensitivity of BIOMED-2 primer system in adult acute lymphoblastic leukemia (AIJ,) patients Ig gene rearrangement, and to analyze their frequency, corearrangement pattern, utilization of V, D and J genes and composition of junctional regions. Methods Amplification of rearranged IgH (complete and incomplete), IgK, IgK-Kde and IgL was performed in standard PCR in 29 adult ALL patients. Monoclonal PCR products were subjected directly to DNA sequencing. Sequences were identified by comparison with all known human Ig germline sequences to analyze the recombination patterns, somatic mutations and germline gene segments usage. Results IgH, incomplete IgH, IgK, igK-Kde and Igl, rearrangements were found with positive rate of 70.8%, 12.5% , 29.2% , 25.0% and 0 of B-ALL patients, respectively. All B-ALL patients displayed at least one pattern of Ig gene rearrangements. In TALL, one of five patients was found with incomplete IgH rearrangement, two patients were found with IgK rearrangements and two patients were PCR-negative. The sequence analysis showed that the most frequently used V, D, J segments in adult B-ALL patients were from VH3/VH4 families, DH3 family and JH6 family, respectively. Four of five IgK rearrangement used VκI family. 23.5% B-ALL IgH contained scattered replacement mutations with replacement to silent substitution ratio < 1 in complementarity determining regions. Conclusion BIOMED-2 multiplex PCR analysis strategy is a reliable and useful technique in the adult BALL patients.%目的 探讨BIOMED-2引物系统检测成人急性淋巴细胞白血病(ALL)患者Ig基因重排的敏感性,分析Ig基因重排方式、各胚系基因的利用频率等.方法 采用BIOMED-2引物系统扩增29例成人ALL患者Ig重链(IgH)和Ig轻链(IgL)重排基因.将PCR产物直接测序,使用IMGT/V-QUEST等生物信息资源分析B细胞-ALL(B-ALL)患者IgH和IgL基因重排类型、胚系基因片段利用及体细胞突变情况.结果 24

  9. Contribution of Large Genomic Rearrangements in Italian Lynch Syndrome Patients: Characterization of a Novel Alu-Mediated Deletion

    Directory of Open Access Journals (Sweden)

    Francesca Duraturo

    2013-01-01

    Full Text Available Lynch syndrome is associated with germ-line mutations in the DNA mismatch repair (MMR genes, mainly MLH1 and MSH2. Most of the mutations reported in these genes to date are point mutations, small deletions, and insertions. Large genomic rearrangements in the MMR genes predisposing to Lynch syndrome also occur, but the frequency varies depending on the population studied on average from 5 to 20%. The aim of this study was to examine the contribution of large rearrangements in the MLH1 and MSH2 genes in a well-characterised series of 63 unrelated Southern Italian Lynch syndrome patients who were negative for pathogenic point mutations in the MLH1, MSH2, and MSH6 genes. We identified a large novel deletion in the MSH2 gene, including exon 6 in one of the patients analysed (1.6% frequency. This deletion was confirmed and localised by long-range PCR. The breakpoints of this rearrangement were characterised by sequencing. Further analysis of the breakpoints revealed that this rearrangement was a product of Alu-mediated recombination. Our findings identified a novel Alu-mediated rearrangement within MSH2 gene and showed that large deletions or duplications in MLH1 and MSH2 genes are low-frequency mutational events in Southern Italian patients with an inherited predisposition to colon cancer.

  10. A single oncogenic enhancer rearrangement causes concomitant EVI1 and GATA2 deregulation in leukemia.

    Science.gov (United States)

    Gröschel, Stefan; Sanders, Mathijs A; Hoogenboezem, Remco; de Wit, Elzo; Bouwman, Britta A M; Erpelinck, Claudia; van der Velden, Vincent H J; Havermans, Marije; Avellino, Roberto; van Lom, Kirsten; Rombouts, Elwin J; van Duin, Mark; Döhner, Konstanze; Beverloo, H Berna; Bradner, James E; Döhner, Hartmut; Löwenberg, Bob; Valk, Peter J M; Bindels, Eric M J; de Laat, Wouter; Delwel, Ruud

    2014-04-10

    Chromosomal rearrangements without gene fusions have been implicated in leukemogenesis by causing deregulation of proto-oncogenes via relocation of cryptic regulatory DNA elements. AML with inv(3)/t(3;3) is associated with aberrant expression of the stem-cell regulator EVI1. Applying functional genomics and genome-engineering, we demonstrate that both 3q rearrangements reposition a distal GATA2 enhancer to ectopically activate EVI1 and simultaneously confer GATA2 functional haploinsufficiency, previously identified as the cause of sporadic familial AML/MDS and MonoMac/Emberger syndromes. Genomic excision of the ectopic enhancer restored EVI1 silencing and led to growth inhibition and differentiation of AML cells, which could be replicated by pharmacologic BET inhibition. Our data show that structural rearrangements involving the chromosomal repositioning of a single enhancer can cause deregulation of two unrelated distal genes, with cancer as the outcome.

  11. T细胞受体γ引物组合检测蕈样肉芽肿基因重排的研究%Application of BIOMED-2 primers in the detection of T cell receptor γ gene rearrangements in patients with mycosis fungoides

    Institute of Scientific and Technical Information of China (English)

    陈柳青; 陈金波; 段逸群; 李东升; 董碧麟; 张红梅; 俞鑫

    2013-01-01

    Objective To estimate the value of BIOMED-2 primers for the detection of T cell receptor γ (TCR-γ) gene rearrangements in different types of specimens from patients with mycosis fungoides (MF).Methods Totally,15 paraffin-embedded tissue specimens,14 fresh tissue specimens and 18 whole blood specimens were obtained from 28 patients with MF,and subjected to DNA extraction.BIOMED-2 multiplex PCR tubes TCRγ (A+B) were used for the analysis of TCRγgene rearrangements.Data were processed by SPSS 13.0 software,and statistical analysis was done by chi-square test and Fisher's exact probability test.Results TCR-γ gene rearrangements were detected in 3 paraffin-embedded tissue specimens,11 fresh tissue specimens and 12 blood specimens,with significant differences in the detection rate between the three samples (x2 =13.047,P < 0.01).The fresh tissue samples showed a significantly higher detection rate than the paraffin-embedded tissue samples (X2 =12.523,P < 0.01).The detection rate of TCRγgene rearrangements was 3/6 in paraffin-embedded tissue samples collected in 2011,significantly higher than that in the other 9 paraffin-embedded tissue samples collected before 2011 (Fisher's exact probability test,P =0.044),but similar to that in 14 fresh tissue specimens (12/14,Fisher's exact probability test,P =0.044).Decreased detection rate of TCRγ gene rearrangements was observed in blood samples compared with fresh tissue specimens,but no statistical difference was observed between the two types of specimens (x2 =2.358,P > 0.05).Conclusions BIOMED-2 multiplex PCR tubes TCRγ(A+B) are suitable for the detection of clonal rearrangements of TCRγgene in different types of specimens,especially in fresh tissue specimens,from patients with MF.%目的 探讨BIOMED-2系统T细胞受体(TCR)γ引物组合在蕈样肉芽肿(MF)患者不同来源标本中TCRγ基因重排检测中的价值.方法 收集28例MF患者15份石蜡组织样本、14份新鲜皮损及18份全血

  12. Assessment of BIOMED-2 assays for detection of clonal Ig gene rearrangements in mature B-cell lymphomas%BIOMED-2聚合酶链反应Ig基因重排对成熟非霍奇金B细胞淋巴瘤诊断的价值

    Institute of Scientific and Technical Information of China (English)

    张婧; 吴迎辉; 孔海鹰; 周小鸽; 金哈斯; 吴晓明; 张丹丹; 宫丽平

    2009-01-01

    目的 探讨BIOMED-2聚合酶链反应(PCR)在成熟非霍奇金B细胞淋巴瘤(B-NHL)诊断中的价值.方法 收集成熟B-NHL组织标本72例,其中弥漫性大B细胞淋巴瘤37例,黏膜相关淋巴组织结外边缘区淋巴瘤35例为研究对象,并以反应性增生病变25例作为对照.提取以上组织的DNA,并以PCR来检测其完整性和可扩增性,选取质量合格的DNA.85.6%(83/97)的样品DNA长度>300 bp,其中60例成熟B-NHL和23例反应性增生可用于BIOMED-2 PCR检测免疫球蛋白重链(IgH)和kappa轻链(IgK)基因重排的克隆性.结果 利用BIOMED-2 PCR检测的60例成熟B-NHL中,57例存在Ig基因的克隆性重排,其检测敏感性为95%,23例反应性增生病例中未出现Ig基因的克隆性重排,其检测特异性为100%.结论 BIOMED-2 PCR适用于石蜡包埋组织.该方法具有很高的敏感性和特异性,对成熟B-NHL诊断的辅助价值很高.%Objective To evaluate the efficiency of the BIOMED-2 PCR assay and its implication in the diagnosis of mature B-cell non-Hodgkin's lymphomas. Methods Clinical, morphological and immunohistochemical features of 72 cases of non-Hodgkin's lymphomas were studied, including 25 reactive lymphoid hyperplasia, 37 diffuse large B cell lymphomas (DLBCL) and 35 extranodal marginal zone lymphomas of mucosa associated lymphoid tissues (MALT lymphoma and in addition, 25 cases of reactive lymphoid hyperplasia were used as the controls). DNA was exacted from the paraffin embedded formalin fixed tissue blocks and the quality of DNA was assessed using the BIOMED-2 specimen control reaction. Adequate samples were then analyzed by BIOMED-2 for immunoglobulin heavy and kappa light chain rearrangements. Results Adequate DNA was obtained in 83 of 97 samples, including 60 mature B cell lymphomas and 23 reactive lymphoid hyperplasia. Clonal B-cell gene rearrangements were detected in 57 of 60(95%) lymphomas. In contrast, clonal Ig gene rearrangements were not detected in any of the 23

  13. Generation and Analysis of Transposon Ac/Ds-Induced Chromosomal Rearrangements in Rice Plants.

    Science.gov (United States)

    Xuan, Yuan Hu; Peterson, Thomas; Han, Chang-Deok

    2016-01-01

    Closely-located transposable elements (TEs) have been known to induce chromosomal breakage and rearrangements via alternative transposition. To study genome rearrangements in rice, an Ac/Ds system has been employed. This system comprises an immobile Ac element expressed under the control of CaMV 35S promoter, and a modified Ds element. A starter line carried Ac and a single copy of Ds at the OsRLG5 (Oryza sativa receptor-like gene 5). To enhance the transpositional activity, seed-derived calli were cultured and regenerated into plants. Among 270 lines regenerated from the starter, one line was selected that contained a pair of inversely-oriented Ds elements at the OsRLG5 (Oryza sativa receptor-like gene 5). The selected line was again subjected to tissue culture to obtain a regenerant population. Among 300 regenerated plants, 107 (36 %) contained chromosomal rearrangements including deletions, duplications, and inversions of various sizes. From 34 plants, transposition mechanisms leading to such genomic rearrangements were analyzed. The rearrangements were induced by sister chromatid transposition (SCT), homologous recombination (HR), and single chromatid transposition (SLCT). Among them, 22 events (65 %) were found to be transmitted to the next generation. These results demonstrate a great potential of tissue culture regeneration and the Ac/Ds system in understanding alternative transposition mechanisms and in developing chromosome engineering in plants.

  14. Generation and Analysis of Transposon Ac/Ds-Induced Chromosomal Rearrangements in Rice Plants.

    Science.gov (United States)

    Xuan, Yuan Hu; Peterson, Thomas; Han, Chang-Deok

    2016-01-01

    Closely-located transposable elements (TEs) have been known to induce chromosomal breakage and rearrangements via alternative transposition. To study genome rearrangements in rice, an Ac/Ds system has been employed. This system comprises an immobile Ac element expressed under the control of CaMV 35S promoter, and a modified Ds element. A starter line carried Ac and a single copy of Ds at the OsRLG5 (Oryza sativa receptor-like gene 5). To enhance the transpositional activity, seed-derived calli were cultured and regenerated into plants. Among 270 lines regenerated from the starter, one line was selected that contained a pair of inversely-oriented Ds elements at the OsRLG5 (Oryza sativa receptor-like gene 5). The selected line was again subjected to tissue culture to obtain a regenerant population. Among 300 regenerated plants, 107 (36 %) contained chromosomal rearrangements including deletions, duplications, and inversions of various sizes. From 34 plants, transposition mechanisms leading to such genomic rearrangements were analyzed. The rearrangements were induced by sister chromatid transposition (SCT), homologous recombination (HR), and single chromatid transposition (SLCT). Among them, 22 events (65 %) were found to be transmitted to the next generation. These results demonstrate a great potential of tissue culture regeneration and the Ac/Ds system in understanding alternative transposition mechanisms and in developing chromosome engineering in plants. PMID:27557685

  15. 利用Fine-tiling aCGH分析TCR基因重排鉴定T细胞白血病克隆%Analysis of TCR gene rearrangement for identification of T cell leukemia clone by using Fine-tiling aCGH

    Institute of Scientific and Technical Information of China (English)

    郑海涛; 叶铁真; 陈少华; 杨力建; 卢育洪; 李扬秋

    2011-01-01

    AIM: To establish a new method which analyzes T cell receptor (TCR) gene rearrangement for identification of T cells acute lymphoblastic leukemia (T-ALL)clone, it will provide the basis for the study of T-ALL including the chromosome translocation involving TCR loci.METHODS: Total DNA was isolated from peripheral blood mononuclear cells (PBMC) of one case with T-ALL. Using the fine-tiling array comparative genomic hybridization (finetiling aCGH) to analyze the genomic DNA differences of the case and control group, we could find the breakpoints and their position in the chromosomes. According to the preliminary results, we could design the specific primers for the positions of the breakpoints relative to sequence. Furthermore, the ligation-mediated PCR (LM-PCR) and sequence analysis were used to identify the TCR gene rearrangement.And TCR gene expression was detected by RT-PCR. RESULTS: The fine-tiling aCGH results of the T-ALL showed that the TCRα/δ locus of chromosome 14 appeared four breakpoints, corresponding to TCR Vδ1, Vδ2, Jδl and Jδ2.By LM-PCR, sequencing and sequence analysis, TCR gene of the case of T-ALL was involved in Vδ1Dδ2Dδ3Jδl,Vδ2Dδ3Jδ2 rearrangement. RT-PCR results also confirmed the expression of these TCR gene rearrangements. CONCLUSION: The results demonstrated that fine-tiling aCGH and LM-PCR techniques could be used to identify the TCR gene rearrangement as one of the best perfect methods.And it was also a way to find some fusion genes involving in TCR gene.%目的:建立基于分析T细胞受体(TCR)基因重排而确定T细胞-急性淋巴细胞白血病(T-ALL)克隆的新方法,为研究T-ALL中涉及TCR基因位点的染色体易位提供基础.方法:提取1例T-ALL患者外周血单个核细胞(PBMC)的总DNA,利用精细定位的寡核苷酸阵列比较基因组杂交(fine-tiling aCGH)分析样本与对照组基因组DNA的差异,了解不同染色体上可能的断裂点和具体的位点,根据所提供的初步结果,

  16. Rearrangement of cluster structure during fission processes

    DEFF Research Database (Denmark)

    Lyalin, Andrey G.; Obolensky, Oleg I.; Solov'yov, Andrey V.;

    2004-01-01

    groups of atoms from the parent cluster is largely independent of the isomer form of the parent cluster. The importance of rearrangement of the cluster structure during the fission process is elucidated. This rearrangement may include transition to another isomer state of the parent cluster before actual......Results of molecular dynamics simulations of fission reactions $Na_10^2+ -->Na_7^++ Na_3^+ and Na_18^2+--> 2Na_9^+ are presented. The dependence of the fission barriers on the isomer structure of the parent cluster is analysed. It is demonstrated that the energy necessary for removing homothetic...

  17. Recent Developments in the Reformatsky-Claisen Rearrangement

    Directory of Open Access Journals (Sweden)

    Susumi Hatakeyama

    2012-11-01

    Full Text Available The rearrangement of allyl a-bromoacetates with Zn dust is known as the Reformatsky-Claisen rearrangement. Whereas the Ireland-Claisen rearrangement has been widely used in the synthesis of a diverse range of natural products, the Zn-mediated Reformatsky-Claisen rearrangement has not been utilized so often. In this article, we will provide an overview of recent advances in the Reformatsky-Claisen rearrangement field, including the In-mediated Reformatsky-Claisen rearrangement we have recently developed.

  18. A single oncogenic enhancer rearrangement causes concomitant EVI1 and GATA2 deregulation in leukemia

    NARCIS (Netherlands)

    Gröschel, Stefan; Sanders, Mathijs A; Hoogenboezem, Remco; de Wit, Elzo; Bouwman, Britta A M; Erpelinck, Claudia; van der Velden, Vincent H J; Havermans, Marije; Avellino, Roberto; van Lom, Kirsten; Rombouts, Elwin J; van Duin, Mark; Döhner, Konstanze; Beverloo, H Berna; Bradner, James E; Döhner, Hartmut; Löwenberg, Bob; Valk, Peter J M; Bindels, Eric M J; de Laat, Wouter; Delwel, Ruud

    2014-01-01

    Chromosomal rearrangements without gene fusions have been implicated in leukemogenesis by causing deregulation of proto-oncogenes via relocation of cryptic regulatory DNA elements. AML with inv(3)/t(3;3) is associated with aberrant expression of the stem-cell regulator EVI1. Applying functional geno

  19. 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...

  20. ROS1-rearranged lung cancer: a clinicopathologic and molecular study of 15 surgical cases.

    Science.gov (United States)

    Yoshida, Akihiko; Kohno, Takashi; Tsuta, Koji; Wakai, Susumu; Arai, Yasuhito; Shimada, Yoko; Asamura, Hisao; Furuta, Koh; Shibata, Tatsuhiro; Tsuda, Hitoshi

    2013-04-01

    Recent discovery of ROS1 gene fusion in a subset of lung cancers has raised clinical interest, because ROS1 fusion-positive cancers are reportedly sensitive to kinase inhibitors. To better understand these tumors, we examined 799 surgically resected non-small cell lung cancers by reverse transcriptase polymerase chain reaction and identified 15 tumors harboring ROS1 fusion transcripts (2.5% of adenocarcinomas). The most frequent fusion partner was CD74 followed by EZR. The affected patients were often younger nonsmoking female individuals, and they had overall survival rates similar to those of the ROS1 fusion-negative cancer patients. All the ROS1 fusion-positive tumors were adenocarcinomas except 1, which was an adenosquamous carcinoma. Histologic examination identified an at least focal presence of either solid growth with signet-ring cells or cribriform architecture with abundant extracellular mucus in 53% of the cases. These 2 patterns are reportedly also characteristic of anaplastic lymphoma kinase (ALK)-rearranged lung cancers, and our data suggest a phenotypic resemblance between the ROS1-rearranged and ALK-rearranged tumors. All tumors except 1 were immunoreactive to thyroid transcription factor-1. Fluorescence in situ hybridization using ROS1 break-apart probes revealed positive rearrangement signals in 23% to 93% of the tumor cells in ROS1 fusion-positive cancers, which were readily distinguished using a 15% cutoff value from 50 ROS1 fusion-negative tumors tested, which showed 0% to 6% rearrangement signals. However, this perfect test performance was achieved only when isolated 3' signals were included along with classic split signals in the definition of rearrangement positivity. Fluorescence in situ hybridization signal patterns were unrelated to 5' fusion partner genes. All ROS1 fusion-positive tumors lacked alteration of EGFR, KRAS, HER2, ALK, and RET genes. PMID:23426121

  1. Dynamics of genome rearrangement in bacterial populations.

    Directory of Open Access Journals (Sweden)

    Aaron E Darling

    Full Text Available Genome structure variation has profound impacts on phenotype in organisms ranging from microbes to humans, yet little is known about how natural selection acts on genome arrangement. Pathogenic bacteria such as Yersinia pestis, which causes bubonic and pneumonic plague, often exhibit a high degree of genomic rearrangement. The recent availability of several Yersinia genomes offers an unprecedented opportunity to study the evolution of genome structure and arrangement. We introduce a set of statistical methods to study patterns of rearrangement in circular chromosomes and apply them to the Yersinia. We constructed a multiple alignment of eight Yersinia genomes using Mauve software to identify 78 conserved segments that are internally free from genome rearrangement. Based on the alignment, we applied Bayesian statistical methods to infer the phylogenetic inversion history of Yersinia. The sampling of genome arrangement reconstructions contains seven parsimonious tree topologies, each having different histories of 79 inversions. Topologies with a greater number of inversions also exist, but were sampled less frequently. The inversion phylogenies agree with results suggested by SNP patterns. We then analyzed reconstructed inversion histories to identify patterns of rearrangement. We confirm an over-representation of "symmetric inversions"-inversions with endpoints that are equally distant from the origin of chromosomal replication. Ancestral genome arrangements demonstrate moderate preference for replichore balance in Yersinia. We found that all inversions are shorter than expected under a neutral model, whereas inversions acting within a single replichore are much shorter than expected. We also found evidence for a canonical configuration of the origin and terminus of replication. Finally, breakpoint reuse analysis reveals that inversions with endpoints proximal to the origin of DNA replication are nearly three times more frequent. Our findings

  2. Recurrent rearrangement during adaptive evolution in an interspecific yeast hybrid suggests a model for rapid introgression.

    Directory of Open Access Journals (Sweden)

    Barbara Dunn

    2013-03-01

    Full Text Available Genome rearrangements are associated with eukaryotic evolutionary processes ranging from tumorigenesis to speciation. Rearrangements are especially common following interspecific hybridization, and some of these could be expected to have strong selective value. To test this expectation we created de novo interspecific yeast hybrids between two diverged but largely syntenic Saccharomyces species, S. cerevisiae and S. uvarum, then experimentally evolved them under continuous ammonium limitation. We discovered that a characteristic interspecific genome rearrangement arose multiple times in independently evolved populations. We uncovered nine different breakpoints, all occurring in a narrow ~1-kb region of chromosome 14, and all producing an "interspecific fusion junction" within the MEP2 gene coding sequence, such that the 5' portion derives from S. cerevisiae and the 3' portion derives from S. uvarum. In most cases the rearrangements altered both chromosomes, resulting in what can be considered to be an introgression of a several-kb region of S. uvarum into an otherwise intact S. cerevisiae chromosome 14, while the homeologous S. uvarum chromosome 14 experienced an interspecific reciprocal translocation at the same breakpoint within MEP2, yielding a chimaeric chromosome; these events result in the presence in the cell of two MEP2 fusion genes having identical breakpoints. Given that MEP2 encodes for a high-affinity ammonium permease, that MEP2 fusion genes arise repeatedly under ammonium-limitation, and that three independent evolved isolates carrying MEP2 fusion genes are each more fit than their common ancestor, the novel MEP2 fusion genes are very likely adaptive under ammonium limitation. Our results suggest that, when homoploid hybrids form, the admixture of two genomes enables swift and otherwise unavailable evolutionary innovations. Furthermore, the architecture of the MEP2 rearrangement suggests a model for rapid introgression, a

  3. Mutations and Rearrangements in the Genome of Sulfolobus solfataricus P2

    DEFF Research Database (Denmark)

    Redder, P.; Garrett, R. A.

    2006-01-01

    of different types of mutation and possible rearrangements that can occur in the genome, the pyrEF locus was examined for mutations that were isolated after selection with 5-fluoroorotic acid. About two-thirds of the 130 mutations resulted from insertions of mobile elements, including insertion sequence (IS...... deletions, insertions, and a duplication, were observed, and about one-fifth of the mutations occurred elsewhere in the genome, possibly in an orotate transporter gene. One mutant exhibited a 5-kb genomic rearrangement at the pyrEF locus involving a two-step IS element-dependent reaction, and its boundaries......The genome of Sulfolobus solfataricus P2 carries a larger number of transposable elements than any other sequenced genome from an archaeon or bacterium and, as a consequence, may be particularly susceptible to rearrangement and change. In order to gain more insight into the natures and frequencies...

  4. Breaking Good: Accounting for Fragility of Genomic Regions in Rearrangement Distance Estimation.

    Science.gov (United States)

    Biller, Priscila; Guéguen, Laurent; Knibbe, Carole; Tannier, Eric

    2016-01-01

    Models of evolution by genome rearrangements are prone to two types of flaws: One is to ignore the diversity of susceptibility to breakage across genomic regions, and the other is to suppose that susceptibility values are given. Without necessarily supposing their precise localization, we call "solid" the regions that are improbably broken by rearrangements and "fragile" the regions outside solid ones. We propose a model of evolution by inversions where breakage probabilities vary across fragile regions and over time. It contains as a particular case the uniform breakage model on the nucleotidic sequence, where breakage probabilities are proportional to fragile region lengths. This is very different from the frequently used pseudouniform model where all fragile regions have the same probability to break. Estimations of rearrangement distances based on the pseudouniform model completely fail on simulations with the truly uniform model. On pairs of amniote genomes, we show that identifying coding genes with solid regions yields incoherent distance estimations, especially with the pseudouniform model, and to a lesser extent with the truly uniform model. This incoherence is solved when we coestimate the number of fragile regions with the rearrangement distance. The estimated number of fragile regions is surprisingly small, suggesting that a minority of regions are recurrently used by rearrangements. Estimations for several pairs of genomes at different divergence times are in agreement with a slowly evolvable colocalization of active genomic regions in the cell.

  5. Comparative analysis of clinicoradiologic characteristics of lung adenocarcinomas with ALK rearrangements or EGFR mutations

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, J.Y.; Zheng, J.; Chen, X.; Zhou, J.Y. [Zhejiang University, Department of Respiratory Disease, Thoracic Disease Center, First Affiliated Hospital, College of Medicine, Hangzhou (China); Yu, Z.F.; Xiao, W.B.; Jiang, L.N. [Zhejiang University, Department of Radiology, First Affiliated Hospital, College of Medicine, Hangzhou (China); Zhao, J.; Sun, K.; Wang, B.; Ding, W. [Zhejiang University, Department of Pathology, First Affiliated Hospital, College of Medicine, Hangzhou (China)

    2015-05-01

    To compare the clinicoradiologic features of tumours with echinoderm anaplastic lymphoma kinase (ALK) rearrangements, epidermal growth factor receptor (EGFR) mutations, or wild type (WT) for both genes in a cohort of patients with lung adenocarcinoma to identify useful characteristics of different gene statuses. In 346 lung adenocarcinoma patients, ALK rearrangements were confirmed with fluorescence in situ hybridisation, and EGFR mutations were determined by pyrosequencing assay. Patients were divided into three groups: ALK rearrangement (ALK+ group, n = 48), EGFR mutation (EGFR+ group, n = 166), and WT for both genes (WT group, n = 132). Chest computed tomography (CT) examinations were performed in all patients. The percentages of ground-glass opacity volume (pGGO) and tumour shadow disappearance rate (TDR) were measured using semi-automated nodule assessment software. The pGGO was significantly lower in the ALK+ group (25.1 % ± 24.3) than in the EGFR+ group (37.2 % ± 25.7, p < 0.001) and the WT group (36.1 % ± 24.6, p = 0.001). The TDR in the ALK+ group (17.3 % ± 25.1) was significantly lower than in the EGFR+ group (26.8 % ± 24.9, p = 0.002) and the WT group (25.7 % ± 24.6, p = 0.003). Solid pattern with lower incidence of lobulated border, finely spiculated margins, pleural retraction, and bubble-like lucency on CT imaging are the main characteristics of ALK rearrangement tumours. (orig.)

  6. BRCA sequencing and large rearrangement testing in young Black women with breast cancer

    OpenAIRE

    Pal, Tuya; Bonner, Devon; Cragun, Deborah; Johnson, Sharland; Akbari, Mohammad; Servais, Lily; Narod, Steven; Vadaparampil, Susan

    2013-01-01

    Young Black women in the United States are disproportionately afflicted with breast cancer, a proportion of which may be due to BRCA1 and BRCA2 (BRCA) gene mutations. In a cancer registry-based sample of young Black women with breast cancer, we evaluated: (1) the prevalence of BRCA mutations detected through full gene sequencing and large rearrangements testing and (2) proportions that accessed genetic services pre-dating study enrollment. Black women diagnosed with invasive breast cancer ≤ag...

  7. Detection of Gene Rearrangement in Bone Marrow of Patients with Non Hodgkin's Lymphoma by BIOMED-2 Protocols%BIOMED-2方法检测恶性淋巴瘤骨髓侵犯的基因重排研究

    Institute of Scientific and Technical Information of China (English)

    童奕; 乔纯; 吴若淇; 刘澎; 周新

    2011-01-01

    This study was purposed to explore the feasibility of BIOMED-2 protocols for detection of immunoglobin (IG) and T-cell receptor (TCR) gene clonal rearrangement in bone marrow of Non-Hodgkin's lymphoma ( NHL) patients, and to evaluate its clinical value. Gene clonal rearrangment(IGH,IGK,IGL,TCRf3,TCRy,TCR8) was detected by using BIOMED-2 protocols in 73 bone marrow examples of NHL patients. The PCR results were compared with the cytomorphologic examination of bone marrow. The correlation between PCR detection results and clinical stage, pathological factors were also evaluated. The results showed that clonal IG or TCR gene rearrangements were found in 31 of 73 cases(42.5% ), higher than the positive rate of cytological analysis(24.7% , 18/73, p<0.05). IG/TCR clonality rates were 40.0% (22/55) for B-NHL and 50% (9/18) for T-NHL. IG/TCR clonality rates detected in patients with BI/IV stage were higher than those with I / II stage(p <0.05). It is concluded that BIOMED-2 protocols are effective methods for detection of abnormalities in bone marrow in patients with lymphoma, and are superior to cytomorphologic examination. The positive rate of PCR detection is correlated with Ann Arbor stage, but is not related with malignant degree, age, treatment status, B symptoms or the involvement of spleen.%本研究探讨BIOMED-2方法检测非霍奇金淋巴瘤(NHL)患者骨髓中免疫球蛋白(IG)和T细胞受体(TCR)基因克隆性重排的可行性,并初步评价其临床价值.采用BIOMED-2系统检测73例NHL( B-NHL 55例,T-NHL 18例)患者骨髓中IGH、IGK、IGL基因和TCRβ、TCRγ、TCRδ基因的克隆性重排,与骨髓穿刺细胞形态学进行比较,评价其与病理特征、临床分期等的相关性.结果表明:73例NHL中31例检测出IG或TCR基因重排,阳性率42.5%,高于骨髓穿刺细胞形态学阳性率24.7% (18/73),差异具有统计学意义(p<0.05);其中B-NHL阳性率为40.0% (22/55),T-NHL阳性率为50.0% (9/18),两

  8. Antibody-Based Detection of ERG Rearrangement-Positive Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Kyung Park

    2010-07-01

    Full Text Available TMPRSS2-ERG gene fusions occur in 50% of prostate cancers and result in the overexpression of a chimeric fusion transcript that encodes a truncated ERG product. Previous attempts to detect truncated ERG products have been hindered by a lack of specific antibodies. Here, we characterize a rabbit anti-ERG monoclonal antibody (clone EPR 3864; Epitomics, Burlingame, CA using immunoblot analysis on prostate cancer cell lines, synthetic TMPRSS2-ERG constructs, chromatin immunoprecipitation, and immunofluorescence. We correlated ERG protein expression with the presence of ERG gene rearrangements in prostate cancertissues using a combined immunohistochemistry(IHC and fluorescence in situ hybridization (FISH analysis. We independently evaluated two patient cohorts and observed ERG expression confined to prostate cancer cells and high-grade prostatic intraepithelial reoplasia associated with ERG-positive cancer, as well as vessels and lymphocytes (where ERG has a known biologic role. Image analysis of 131 cases demonstrated nearly 100% sensitivity for detecting ERG rearrangement prostate cancer, with only 2 (1.5% of 131 cases demonstrating strong ERG protein expression without any known ERG gene fusion. The combired pathology evaluation of 207 patient tumors for ERG protein expression had 95.7% sensitivity and 96.5% specificity for determining ERG rearrangement prostate cancer. Ir conclusion, this study qualifies a specific anti-ERG antibody and demonstrates exquisite association between ERG gene rearrangement and truncated ERG protein product expression. Giver the ease of performing IHC versus FISH, ERG protein expression may be useful for molecularly subtypirg prostate cancer based or ERG rearrangement status and suggests clinical utility it prostate needle biopsy evaluation.

  9. Enhancing bilinear subspace learning by element rearrangement.

    Science.gov (United States)

    Xu, Dong; Yan, Shuicheng; Lin, Stephen; Huang, Thomas S; Chang, Shih-Fu

    2009-10-01

    The success of bilinear subspace learning heavily depends on reducing correlations among features along rows and columns of the data matrices. In this work, we study the problem of rearranging elements within a matrix in order to maximize these correlations so that information redundancy in matrix data can be more extensively removed by existing bilinear subspace learning algorithms. An efficient iterative algorithm is proposed to tackle this essentially integer programming problem. In each step, the matrix structure is refined with a constrained Earth Mover's Distance procedure that incrementally rearranges matrices to become more similar to their low-rank approximations, which have high correlation among features along rows and columns. In addition, we present two extensions of the algorithm for conducting supervised bilinear subspace learning. Experiments in both unsupervised and supervised bilinear subspace learning demonstrate the effectiveness of our proposed algorithms in improving data compression performance and classification accuracy.

  10. Catalytic synthesis of amides via aldoximes rearrangement.

    Science.gov (United States)

    Crochet, Pascale; Cadierno, Victorio

    2015-02-14

    Amide bond formation reactions are among the most important transformations in organic chemistry because of the widespread occurrence of amides in pharmaceuticals, natural products and biologically active compounds. The Beckmann rearrangement is a well-known method to generate secondary amides from ketoximes. However, under the acidic conditions commonly employed, aldoximes RHC=NOH rarely rearrange into the corresponding primary amides RC(=O)NH2. In recent years, it was demonstrated that this atom-economical transformation can be carried out efficiently and selectively with the help of metal catalysts. Several homogeneous and heterogenous systems have been described. In addition, protocols offering the option to generate the aldoximes in situ from the corresponding aldehydes and hydroxylamine, or even from alcohols, have also been developed, as well as a series of tandem processes allowing the access to N-substituted amide products. In this Feature article a comprehensive overview of the advances achieved in this particular research area is presented.

  11. Zinc Finger Nuclease induced DNA double stranded breaks and rearrangements in MLL

    Energy Technology Data Exchange (ETDEWEB)

    Do, To Uyen [Graduate Group in Immunology, University of California Davis, Davis, CA 95616 (United States); Department of Radiation Oncology, University of California Davis, Sacramento CA 95817 (United States); Ho, Bay; Shih, Shyh-Jen [Department of Radiation Oncology, University of California Davis, Sacramento CA 95817 (United States); Vaughan, Andrew, E-mail: Andrew.vaughan@ucdmc.ucdavis.edu [Graduate Group in Immunology, University of California Davis, Davis, CA 95616 (United States); Department of Radiation Oncology, University of California Davis, Sacramento CA 95817 (United States)

    2012-12-15

    Highlights: ► A Zinc Finger Nuclease (ZFN) targeting a leukemogenic hot spot for rearrangement in MLL is created. ► The novel ZFN efficiently cleaves MLL exon 13. ► Despite MLL cleavage and evidence of mis-repair, no leukemogenic translocations were produced. ► MLL cleavage alone is insufficient to generate leukemogenic translocations. - Abstract: Radiation treatment or chemotherapy has been linked with a higher risk of secondary cancers such as therapy related Acute Myeloid Leukemia (tAML). Several of these cancers have been shown to be correlated to the introduction of double stranded breaks (DSB) and rearrangements within the Mixed Lineage Leukemia (MLL) gene. We used Zinc Finger Nucleases (ZFNs) to introduce precise cuts within MLL to examine how a single DNA DSB might lead to chromosomal rearrangements. A ZFN targeting exon 13 within the Breakpoint Cluster Region of MLL was transiently expressed in a human lymphoblast cell line originating from a CML patient. Although FISH analysis showed ZFN DSB at this region increased the rate of MLL fragmentation, we were unable to detect leukemogenic rearrangements or translocations via inverse PCR. Interestingly, gene fragmentation as well as small interstitial deletions, insertions and base substitutions increased with the inhibition of DNA-PK, suggesting repair of this particular DSB is linked to non-homologous end joining (NHEJ). Although mis-repair of DSBs may be necessary for the initiation of leukemogenic translocations, a MLL targeted DNA break alone is insufficient.

  12. Simple and rapid in vivo generation of chromosomal rearrangements using CRISPR/Cas9 technology.

    Science.gov (United States)

    Blasco, Rafael B; Karaca, Elif; Ambrogio, Chiara; Cheong, Taek-Chin; Karayol, Emre; Minero, Valerio G; Voena, Claudia; Chiarle, Roberto

    2014-11-20

    Generation of genetically engineered mouse models (GEMMs) for chromosomal translocations in the endogenous loci by a knockin strategy is lengthy and costly. The CRISPR/Cas9 system provides an innovative and flexible approach for genome engineering of genomic loci in vitro and in vivo. Here, we report the use of the CRISPR/Cas9 system for engineering a specific chromosomal translocation in adult mice in vivo. We designed CRISPR/Cas9 lentiviral vectors to induce cleavage of the murine endogenous Eml4 and Alk loci in order to generate the Eml4-Alk gene rearrangement recurrently found in non-small-cell lung cancers (NSCLCs). Intratracheal or intrapulmonary inoculation of lentiviruses induced Eml4-Alk gene rearrangement in lung cells in vivo. Genomic and mRNA sequencing confirmed the genome editing and the production of the Eml4-Alk fusion transcript. All mice developed Eml4-Alk-rearranged lung tumors 2 months after the inoculation, demonstrating that the CRISPR/Cas9 system is a feasible and simple method for the generation of chromosomal rearrangements in vivo.

  13. Molecular characterization of a balanced rearrangement of chromosome 12 in two siblings with Noonan syndrome.

    Science.gov (United States)

    Yatsenko, Svetlana A; del Valle Torrado, Maria; Fernandes, Priscilla H; Wiszniewska, Joanna; Gallego, Marta; Herrera, Jorge; Bacino, Carlos A

    2009-12-01

    The etiology of Noonan syndrome (NS) has been greatly elucidated with the discovery of the disease causative genes PTPN11, KRAS, SOS1, and RAF1, all involved in the RAS/MAPK-signaling cascade. Given that overall mutations are identified in about 70% of patients, identification of other NS associated genes remains a high priority to fully understand the etiopathogenesis of the condition. We report two affected siblings with an apparently balanced rearrangement of chromosome 12 ins(12)(q12p11.2p12.3) which segregates with the Noonan phenotype. The rearrangement was inherited from the phenotypically normal mother who had mosaicism for the derivative chromosome 12. There were no mutations of PTPN11, KRAS, SOS1, or RAF1 genes detected in the probands. Using fluorescence in situ hybridization analysis we identified the three breakpoints involved at 12p12.3, 12p11.2, and 12q12. By microarray analysis, there were no gains or losses near the breakpoints. Neither, the PTPN11 or KRAS region on chromosome 12 was involved in the rearrangement. We hypothesize that other NS candidate gene(s) may be located in the breakpoint regions of chromosome 12 causing the Noonan phenotype in both of these children.

  14. A case report of CIC-rearranged undifferentiated small round cell sarcoma in the cerebrum.

    Science.gov (United States)

    Ito, Mayumi; Ishikawa, Misawo; Kitajima, Masateru; Narita, Jun; Hattori, Shinya; Endo, Otone; Goto, Keisuke

    2016-10-01

    CIC-rearranged undifferentiated small round cell sarcoma (CIC-rearranged USRCS) is a recently established type of Ewing-like small round cell sarcomas, characterized by CIC gene rearrangement, most commonly CIC-DUX4 fusion. This report presents the second case of CIC-rearranged USRCS arising primarily in the cerebrum. A 64-year-old otherwise healthy woman presented with a 1 × 1 cm sized hemorrhagic subcortical tumor in the left temporo-parietal lobe. The tumor repeatedly recurred, and the patient underwent three surgeries, chemotherapy with doxorubicin and ifosfamide, and radiotherapy, as well as gamma knife surgery. Systemic examination revealed no other extracranial masses. Imprint cytology revealed small to moderate-sized round-to-ovoid tumor cells with mild pleomorphism and variations in size and shape. The nuclei contained finely granular chromatin, and some had easily-recognizable nucleoli. The tumor exhibited a mainly cytoplasmic pattern of CD99 immunostaining, rather than a diffuse membranous pattern. The tumor also exhibited diffuse positivity for calretinin and p16, as well as partial positivity for WT1 (nuclear and cytoplasmic staining pattern) and D2-40. FISH assessment showed CIC split signals. In conclusion, CIC-rearranged USRCSs can occur primarily in the cerebrum. It would be impossible to diagnose them through cytology alone, but cytology would be useful to rule out other small round cell brain tumors including gliomas, lymphomas, carcinomas, and germinoma. Immunohistochemical analysis including tests for CD99, calretinin, and WT1 would help to suggest CIC-rearranged USRCSs and distinguish them from Ewing sarcomas. Additionally, immunohistochemistry for p16 might be useful in the diagnosis. Diagn. Cytopathol. 2016;44:828-832. © 2016 Wiley Periodicals, Inc. PMID:27324529

  15. Utility of NUT gene expression and rearrangement in diagnosis of NUT midline carcinoma in upper respiratory tract%睾丸核蛋白表达和基因重排在上呼吸道睾丸核蛋白中线癌中的应用

    Institute of Scientific and Technical Information of China (English)

    方微; Christopher A. French; Michael J. Cameron; 韩一丁; 刘红刚

    2012-01-01

    目的 探讨睾丸核蛋白(NUT)抗体表达及基因重排在上呼吸道NUT中线癌(NMC)中的应用,以及NMC的发病情况、临床病理学特点、诊断及其鉴别诊断.方法 收集北京同仁医院病理科1990年至2010年诊断的上呼吸道小圆细胞型恶性肿瘤163例,包括低分化鳞状细胞癌(31例)及未分化癌(1例)、非角化型未分化鼻咽癌(60例)、小细胞神经内分泌癌(6例)及其他非上皮性小圆细胞型恶性肿瘤(65例).分析其临床特征及病理学特点,行EB病毒编码的小RNA探针(EBER)原位杂交检测及NUT单克隆抗体的免疫组织化学EnVision法染色.NUT抗体阳性表达的病例以荧光原位杂交(FISH)法检测NUT基因重排、以免疫组织化学染色方法标记角蛋白(AEI/AE3、CK7、CK8)、p63及神经内分泌标志物(神经元特异性烯醇化酶、突触素、嗜铬粒素A、S-100蛋白、CD56).结果 (1)3例低分化鳞状细胞癌及1例未分化癌中发现NUT抗体呈强阳性核表达,约占该组病例的12.5% (4/32),占本组上皮性恶性肿瘤的4.1% (4/98),全部病例的2.5% (4/163);其年龄范围为42~59岁;其他各组病例NUT抗体均为阴性;(2)4例NUT抗体阳性表达的病例其瘤细胞均表达角蛋白及p63,而神经内分泌标志物及EBER检测均阴性;(3)4例NUT阳性表达的病例中2例FISH检测证实有NUT基因重排,此2例患者死亡,另2例未检测到NUT基因重排,患者存活(分别为40及12个月).结论 (1)NMC是发生于上呼吸道的少见小圆细胞型恶性肿瘤,既往被归于低分化鳞状细胞癌及未分化癌中,其NUT抗体阳性表达及NUT基因重排阳性;(2)NMC好发于中线器官,特别是鼻腔鼻窦,与EB病毒感染无关,临床病程及预后有所不同;(3)NUT免疫组织化学染色及FISH检测在其诊断及鉴别诊断中发挥主要作用.%Objective To investigate the importance of expression of the NUT gene and its rearrangement in diagnosing NUT midline carcinoma

  16. ETV6-RUNX1 Rearrangement in Tunisian Pediatric B-Lineage Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Abir Gmidène

    2009-01-01

    Full Text Available In this study, Forty-one out of fifty-seven Tunisian children with B-lineage acute lymphoblastic leukemia (B-ALL, and without cytogenetically detectable recurrent abnormalities at the time of the diagnosis, were evaluated by fluorescence in situ hybridization (FISH for the t(12;21. This translocation leads ETV6-RUNX1 (previously TEL-AML1 fusion gene. 16 patients (28% had ETV6-RUNX1 rearrangement. In addition to this rearrangement, two cases showed a loss of the normal ETV6 allele, and three others showed an extra signal of the RUNX1 gene. Seven patients without ETV6-RUNX1 rearrangement showed extra signals of the RUNX1 gene. One out of the 7 patients was also associated with a t(3;12 identified by FISH. This is the first Tunisian study in which we report the incidence of t(12;21 among childhood B-lineage ALL and in which we have found multiple copies of RUNX1. Finally, our findings confirm that additional or secondary genetic changes are commonly encountered in pediatric B-lineage ALL with ETV6-RUNX1 gene fusion which is envisaged to play a pivotal role in disease progression.

  17. Adiabatic Rearrangement of Hollow PV Towers

    Directory of Open Access Journals (Sweden)

    Eric A Hendricks

    2010-10-01

    Full Text Available Diabatic heating from deep moist convection in the hurricane eyewall produces a towering annular structure of elevated potential vorticity (PV. This structure has been referred to as a hollow PV tower. The sign reversal of the radial gradient of PV satisfies the Charney-Stern necessary condition for combined barotropic-baroclinic instability. For thin enough annular structures, small perturbations grow exponentially, extract energy from the mean flow, and lead to hollow tower breakdown, with significant vortex structural and intensity change. The three-dimensional adiabatic rearrangements of two prototypical hurricane-like hollow PV towers (one thick and one thin are examined in an idealized framework. For both hollow towers, dynamic instability causes air parcels with high PV to be mixed into the eye preferentially at lower levels, where unstable PV wave growth rates are the largest. Little or no mixing is found to occur at upper levels. The mixing at lower and middle levels is most rapid for the breakdown of the thin hollow tower, consistent with previous barotropic results. For both hollow towers, this advective rearrangement of PV affects the tropical cyclone structure and intensity in a number of ways. First, the minimum central pressure and maximum azimuthal mean velocity simultaneously decrease, consistent with previous barotropic results. Secondly, isosurfaces of absolute angular momentum preferentially shift inward at low levels, implying an adiabatic mechanism by which hurricane eyewall tilt can form. Thirdly, a PV bridge, similar to that previously found in full-physics hurricane simulations, develops as a result of mixing at the isentropic levels where unstable PV waves grow most rapidly. Finally, the balanced mass field resulting from the PV rearrangement is warmer in the eye between 900 and 700 hPa. The location of this warming is consistent with observed warm anomalies in the eye, indicating that in certain instances the hurricane

  18. Rearrangement of Barcelona serveis municipals customer services

    OpenAIRE

    Fullana Roger, Cristina

    2015-01-01

    This document presents the report for the Final Degree Thesis. The subject of the project is the Rearrangement of the Customer Services of the public company Barcelona Serveis Municipals (B:SM). The project is classified in the Management area and it details the definition and adaptation process of a new model in the customer services of B:SM. The origin of the project stands on the opening of the new Calàbria facilities. The purpose of the project is to identify the problems in the curren...

  19. Chromosomal rearrangement in autotetraploid plants of Arabidopsis thaliana.

    Science.gov (United States)

    Weiss, H; Maluszynska, J

    2000-01-01

    Recent development of cytogenetic techniques has facilitated significant progress in Arabidopsis thaliana karyotype studies. Double-target FISH with rRNA genes provides makers that allow individual chromosome in the genome to be distinguished. Those studies have revealed that the number and position of rDNA loci is ecotype-specific. Arabidopsis is believed to be a true diploid (x = 5) with numerous ecotypes (accessions) and only a very few natural polyploid populations reported. Few studies were undertaken to induce polyploidy in Arabidopsis, however none of those gave the cytogenetic characteristics of polyploid plants. Our analysis of chromosome pairing of colchicine-induced autotetraploid Arabidopsis (Wilna ecotype) revealed preferential bivalent pairing in PMCs (pollen mother cells). In order to attempt to explain this phenomenon, first of all more detailed cytogenetic studies of autopolyploid plants have been undertaken. The localization of 45S and 5S rDNA loci in the diploid and autotetraploid plants revealed that Wilna ecotypes belongs to the group of Arabidopsis accessions with only two 5S rDNA loci present in a genome. Furthermore, the rearrangement of 45S rDNA locus in autopolyploid, when compared to the diploid plants of the same ecotype, was revealed. These results are interesting also in the context of the recently emphasised role of polyploidy in plant evolution and speciation. Arabidopsis, despite having small chromosomes, is a good system to study chromosome behaviour in relation to diploidization of autopolyploids and to evaluate the degree of chromosomal rearrangements during this process. PMID:11433970

  20. 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.

  1. A transgenic system for generation of transposon Ac/Ds-induced chromosome rearrangements in rice

    OpenAIRE

    Yu, Chuanhe; Han, FangPu; Zhang, Jianbo; Birchler, James; Peterson, Thomas

    2012-01-01

    The maize Activator (Ac)/Dissociation (Ds) transposable element system has been used in a variety of plants for insertional mutagenesis. Ac/Ds elements can also generate genome rearrangements via alternative transposition reactions which involve the termini of closely linked transposons. Here, we introduced a transgene containing reverse-oriented Ac/Ds termini together with an Ac transposase gene into rice (Oryza sativa ssp. japonica cv. Nipponbare). Among the transgenic progeny, we identifie...

  2. Delineating Rearrangements in Single Yeast Artificial Chromosomes by Quantitative DNA Fiber Mapping

    OpenAIRE

    Weier, Heinz-Ulrich G.; Greulich-Bode, Karin M.; Wu, Jenny; Duell, Thomas

    2009-01-01

    Cloning of large chunks of human genomic DNA in recombinant systems such as yeast or bacterial artificial chromosomes has greatly facilitated the construction of physical maps, the positional cloning of disease genes or the preparation of patient-specific DNA probes for diagnostic purposes. For this process to work efficiently, the DNA cloning process and subsequent clone propagation need to maintain stable inserts that are neither deleted nor otherwise rearranged. Some regions of the human g...

  3. 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.

  4. 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.

  5. NOTCH2 is neither rearranged nor mutated in t(1;19 positive oligodendrogliomas.

    Directory of Open Access Journals (Sweden)

    Magdalena Benetkiewicz

    Full Text Available The combined deletion of 1p and 19q chromosomal arms is frequent in oligodendrogliomas (OD and has recently been shown to be mediated by an unbalanced t(1;19 translocation. Recent studies of 1p/19q co-deleted OD suggest that the NOTCH2 gene is implicated in oligodendrocyte differentiation and may be involved in this rearrangement. The objective of the present study was to analyze the NOTCH2 locus either as a chromosomal translocation locus that may be altered by the 1p/19q recurrent rearrangement or as a gene that may be inactivated by a two hit process. We performed an array-CGH analysis of 15 ODs presenting 1p/19q co-deletion using a high-density oligonucleotide microarray spanning 1p and 19q pericentromeric regions with 377 bp average probe spacing. We showed that the 1p deletion extends to the centromere of chromosome 1 and includes the entire NOTCH2 gene. No internal rearrangement of this gene was observed. This strongly suggests that the t(1;19 translocation does not lead to an abnormal NOTCH2 structure. The analysis of the entire NOTCH2 coding sequence was performed in four cases and did not reveal any mutation therefore indicating that NOTCH2 does not harbor genetic characteristics of a tumor suppressor gene. Finally, the detailed analysis of chromosome 19 pericentromeric region led to the identification of two breakpoint clusters at 19p12 and 19q11-12. Interestingly, these two regions share a large stretch of homology. Together with previous observations of similarities between chromosome 1 and 19 alphoid sequences, this suggests that the t(1;19 translocation arises from complex intra and interchromosomal rearrangements.This is the first comprehensive deletion mapping by high density oligo-array of the 1p/19q co-deletion in oligodendroglioma tumors using a methodological approach superior to others previously applied. As such this paper provides clear evidence that the NOTCH2 gene is not physically rearranged by t(1;19 translocation of

  6. Bootstrapping phylogenies inferred from rearrangement data

    Directory of Open Access Journals (Sweden)

    Lin Yu

    2012-08-01

    Full Text Available Abstract Background Large-scale sequencing of genomes has enabled the inference of phylogenies based on the evolution of genomic architecture, under such events as rearrangements, duplications, and losses. Many evolutionary models and associated algorithms have been designed over the last few years and have found use in comparative genomics and phylogenetic inference. However, the assessment of phylogenies built from such data has not been properly addressed to date. The standard method used in sequence-based phylogenetic inference is the bootstrap, but it relies on a large number of homologous characters that can be resampled; yet in the case of rearrangements, the entire genome is a single character. Alternatives such as the jackknife suffer from the same problem, while likelihood tests cannot be applied in the absence of well established probabilistic models. Results We present a new approach to the assessment of distance-based phylogenetic inference from whole-genome data; our approach combines features of the jackknife and the bootstrap and remains nonparametric. For each feature of our method, we give an equivalent feature in the sequence-based framework; we also present the results of extensive experimental testing, in both sequence-based and genome-based frameworks. Through the feature-by-feature comparison and the experimental results, we show that our bootstrapping approach is on par with the classic phylogenetic bootstrap used in sequence-based reconstruction, and we establish the clear superiority of the classic bootstrap for sequence data and of our corresponding new approach for rearrangement data over proposed variants. Finally, we test our approach on a small dataset of mammalian genomes, verifying that the support values match current thinking about the respective branches. Conclusions Our method is the first to provide a standard of assessment to match that of the classic phylogenetic bootstrap for aligned sequences. Its

  7. REARRANGEMENT IN THE B-GENOME FROM DIPLOID PROGENITOR TO WHEAT ALLOPOLYPOLID

    Directory of Open Access Journals (Sweden)

    Salina E.A.

    2012-08-01

    Full Text Available Three key periods that were accompanied by considerable rearrangements in the B genome of wheat and its progenitor can be considered. The first period covers the period from the divergence of diploid Triticum and Aegilops species from their common progenitor (2.5–6 million years ago to formation of the tetraploid T. diccocoides (about 500 thousand years ago. Significant genomic rearrangements in the diploid progenitor of the B genome, Ae. speltoides (SS genome, involved a considerable amplification of repeated DNA sequences, which led to an increase in the number of heterochromatin blocks on chromosomes relative to other diploid Aegilops and Triticum species. Our analysis has demonstrated that during this period the Spelt1 repeats intensively amplified as well as several mobile elements proliferated, in particular, the genome-specific gypsy LTR-retrotransposon Fatima and CACTA DNA-transposon Caspar. The second period in the B-genome evolution was associated with the emergence of tetraploid (BBAA genome and its subsequent evolution. The third most important event leading to the next rearrangement of the B genome took place relatively recently, 7000–9500 years ago, being associated with the emergence of hexaploid wheat with the genomic formula BBAADD. The evolution of the B/S genome involved intergenomic and intragenomic translocations and chromosome inversions. So far, five rearrangements in the B-genome chromosomes of polyploid wheats has been observed and described; the majority of them took place during the formation and evolution of tetraploid species. The mapping of the S-genome chromosomes and comparison with the B-genome chromosome maps have demonstrated that individual rearrangements pre-existed in Ae. speltoides; moreover, Ae. speltoides is polymorphic for these rearrangements.Chromosome 5B is nearly 870 Mbp (5BL = 580 Mbp and 5BS = 290 Mbp and is known to carry important genes controlling the key aspects of wheat biology, in

  8. Primary cutaneous diffuse large B-cell lymphoma, leg type: a study of clinicopathology,immunophenotype and gene rearrangement%原发性皮肤腿型弥漫性大B细胞淋巴瘤七例临床病理学及基因重排研究

    Institute of Scientific and Technical Information of China (English)

    王婷婷; 贾玲; 廖文俊; 陈柳青; 陈喜雪; 熊亚; 郝飞; 朱学骏; 杨希川

    2015-01-01

    Objective To study the clinicopathologic features,immunophenotype and gene rearrangement of primary cutaneous diffuse large B-cell lymphoma,leg type (PCLBCL).Methods Seven cases of PCLBCL were enrolled into the study.Clinicopathologic analysis,immunohistochemical staining and gene rearrangement for IgH and Igκ were undertaken in the study.Results All the seven cases were male,and the median age was 72 years.Patients usually presented with multiple purple tumors,nodules,papules and infiltrative plaques.Two patients had a history of leg injury before onset,and one had mosquito bites.Histologically,the tumor involved the dermis and subcutis with dense and diffuse infiltrative pattern composing of centroblasts and/or immunoblasts.Immunohistochemical staining showed that seven cases (7/7) expressed CD20,six (6/6) expressed bcl-2,four (4/4) expressed MUM-1,four (4/5) expressed CD79a,four (4/5) expressed PAX-5 and four (4/6)expressed bcl-6,respectively.All cases did not express CD3ε,CD45RO,CD1O and CD30.IgH gene rearranged bands were detected in three (3/6)cases and Igκ was detected in one (1/5) case.Six of the seven cases died and the remaining patient,who was 44-year-old,was alive after 22 months of follow-up.Conclusions PCLBCL is rare,predominantly affects elderly male patients.PCLBCL has poor prognosis and high mortality,but younger patients seem to have better prognosis.Some cases had a history of trauma or mosquito bites.The relationship between the history and the onset of PCLBCL needs further evaluation.%目的 探讨原发性皮肤腿型弥漫性大B细胞淋巴瘤(PCLBCL)的临床病理学特点.方法 对7例PCLBCL患者的临床病理资料进行分析,并行免疫组织化学染色及IgH和Igκ基因重排检测.结果 7例均为男性,中位年龄72岁,临床表现为多发的紫红色肿块、结节、丘疹、浸润性斑块.2例有外伤史,1例有蚊虫叮咬史.组织学上肿瘤位于真皮及皮下脂肪层,常见无浸润带.瘤细

  9. 利用石蜡包埋组织进行BIOMED-2标准化IG/TCR基因重排检测在淋巴瘤诊断中的意义%Significance of BIOMED-2 standardized IG/TCR gene rearrangement detection in paraffin-embedded section in lymphoma diagnosis

    Institute of Scientific and Technical Information of China (English)

    艾晓非; 付骞千; 王君; 郑迎春; 韩聪; 李庆华; 孙琦; 汝昆

    2014-01-01

    Objective To explore the feasibility of detecting lymphoma with the application of BIOMED-2 standardized immunoglobulin/T cell receptor (IG/TCR) gene rearrangement system in formalin fixed paraffin-embedded (FFPE) tissue samples,and to discuss the relationship between the longest amplification fragment of extracted DNA and positive detection rate of different IGH V-J primers.Methods DNA was extracted from 50 cases of FFPE tissue samples.Multiplex-PCR amplifications were performed and then the IG/TCR gene rearrangements were analyzed using BIOMED-2 standardized clonality analysis system.Results ①When the DNA concentration was diluted to 50-100 ng/μl from 100-500 ng/μtl,the proportion of the longest amplification fragment (300-400 bp) of DNA was improved from 10.0% to 90.0% in 30 cases of diffuse large B cell lymphoma (DLBCL) wax roll samples (P<0.01).The positive rate of IGH+IGK was increased from 46.7% to 83.3%,the difference was statistically significant (P=0.006).The lengths of the longest amplification fragments of DNA were all longer than 300bp in the paraffin section samples of DLBCL.The positive rate of IGH + IGK of these samples was 96.7%.The difference of the positive rate of IGH+IGK between the wax roll samples and the paraffin section samples had no statistical significance (P=0.195).②When the concentration of DNA was high,most of the longest amplification fragments of extracted DNA were 100 bp or 200bp,and the detection rate of short fragment IGH FR3 was more stable than that of long fragment IGH FR1.③The clonality analysis of TCRG+TCRB in all 13 cases of peripheral T cell lymphoma samples showed positive results,while no positive IG/TCR clones were found in 7 cases of reactive lymphoid tissue hyperplasia in control group.Conclusion Dilution of DNA is the only method to improve not only the proportion of longest fragment amplification but also the detection rate of clonality.The detection rate of IGH FR3 would not be affected by the

  10. Level rearrangement in three-body systems

    CERN Document Server

    Richard, Jean-Marc

    2016-01-01

    We study systems of three bosons bound by a long-range interaction supplemented by a short-range potential of variable strength. This generalizes the usual two-body exotic atoms where the Coulomb interaction is modified by nuclear forces at short distances. The energy shift due to the short-range part of the interaction combines two-body terms similar to the ones entering the Trueman-Deser formula, and three-body contributions. A phenomenon of level rearrangement is observed, similar to the Zel'dovich effect, by the onset of an additional stable level which is eventually absorbed by the two-body threshold energy, and can be interpreted as an Efimov-like state of the short-range potential.

  11. ImmunoGlobulin galaxy (IGGalaxy) for simple determination and quantitation of immunoglobulin heavy chain rearrangements from NGS

    NARCIS (Netherlands)

    M.J. Moorhouse (Michael); D. van Zessen (David); H. IJspeert (Hanna); S. Hiltemann (Saskia); S. Horsman (Sebastiaan); P.J. van der Spek (Peter); M. van der Burg (Mirjam); A. Stubbs (Andrew)

    2014-01-01

    textabstractBackground: Sequence analysis of immunoglobulin heavy chain (IGH) gene rearrangements and frequency analysis is a powerful tool for studying the immune repertoire, immune responses and immune dysregulation in health and disease. The challenge is to provide user friendly, secure and repro

  12. Mechanisms for Nonrecurrent Genomic Rearrangements Associated with CMT1A or HNPP: Rare CNVs as a Cause for Missing Heritability

    NARCIS (Netherlands)

    F. Zhang; P. Seeman; P. Liu; M.A.J. Weterman; C. Gonzaga-Jauregui; C.F. Towne; S.D. Batish; E. de Vriendt; P. de Jonghe; B. Rautenstrauss; K.H. Krause; M. Khajavi; J. Posadka; A. Vandenberghe; F. Palau; L. van Maldergem; F. Baas; V. Timmerman; J.R. Lupski

    2010-01-01

    Genomic rearrangements involving the peripheral myelin protein gene (PMP22) in human chromosome 17p12 are associated with neuropathy: duplications cause Charcot-Marie-Tooth disease type IA (CMT1A), whereas deletions lead to hereditary neuropathy with liability to pressure palsies (HNPP). Our previou

  13. Generation of genetically stable recombinant rotaviruses containing novel genome rearrangements and heterologous sequences by reverse genetics.

    Science.gov (United States)

    Navarro, Aitor; Trask, Shane D; Patton, John T

    2013-06-01

    The rotavirus (RV) genome consists of 11 segments of double-stranded RNA (dsRNA). Typically, each segment contains 5' and 3' untranslated regions (UTRs) that flank an open reading frame (ORF) encoding a single protein. RV variants with segments of atypical size owing to sequence rearrangements have been described. In many cases, the rearrangement originates from a partial head-to-tail sequence duplication that initiates after the stop codon of the ORF, leaving the protein product of the segment unaffected. To probe the limits of the RV genome to accommodate additional genetic sequence, we used reverse genetics to insert duplications (analogous to synthetic rearrangements) and heterologous sequences into the 3' UTR of the segment encoding NSP2 (gene 8). The approach allowed the recovery of recombinant RVs that contained sequence duplications (up to 200 bp) and heterologous sequences, including those for FLAG, the hepatitis C virus E2 epitope, and the internal ribosome entry site of cricket paralysis virus. The recombinant RVs grew to high titer (>10(7) PFU/ml) and remained genetically stable during serial passage. Despite their longer 3' UTRs, rearranged RNAs of recombinant RVs expressed wild-type levels of protein in vivo. Competitive growth experiments indicated that, unlike RV segments with naturally occurring sequence duplications, genetically engineered segments were less efficiently packaged into progeny viruses. Thus, features of naturally occurring rearranged segments, other than their increased length, contribute to their enhanced packaging phenotype. Our results define strategies for developing recombinant RVs as expression vectors, potentially leading to next-generation RV vaccines that induce protection against other infectious agents. PMID:23536662

  14. The Superiority of Allogeneic Hematopoietic Stem Cell Transplantation Over Chemotherapy Alone in the Treatment of Acute Myeloid Leukemia Patients with Mixed Lineage Leukemia (MLL) Rearrangements

    Science.gov (United States)

    Yang, Hua; Huang, Sai; Zhu, Cheng-Ying; Gao, Li; Zhu, Hai-Yan; Lv, Na; Jing, Yu; Yu, Li

    2016-01-01

    Background Acute myeloid leukemia (AML) patients with mixed lineage leukemia (MLL) gene rearrangements always had a very poor prognosis. In this study, we report the incidence of MLL rearrangements in AML patients using gene analysis, as well as the clinical significance and prognostic features of these rearrangements. Material/Methods This retrospective study took place from April 2008 to November 2011 in the People’s Liberation Army General Hospital. A total 433 AML patients were screened by multiple nested reverse transcription polymerase chain reaction (RT-PCR) to determine the incidence of the 11 MLL gene rearrangements. There were 68 cases of MLL gene rearrangements, for a positive rate of 15.7%. A total of 24 patients underwent allogeneic hematopoietic stem cell transplantation (Allo-HSCT), and 34 patients received at least 4 cycles of chemotherapy. Ten patients were lost to follow-up. Results The median follow-up was 29 months. The complete remission (CR) rate was 85.4%. The overall survival (OS) was 57.4±5.9 months for the Allo-HSCT group and 21.0±2.1 months for the chemotherapy group. The Allo-HSCT group had superior survival compared with the chemotherapy group (5-year OS: 59±17% vs. 13±8%, P0.05). Multivariate analysis showed that transplantation, platelets >50×109/L at onset, and CR are associated with a better OS in MLL rearranged AML patients. Patients with thrombocytopenia and extramedullary involvement were prone to relapse. Conclusions Our results suggest that Allo-HSCT is superior to chemotherapy alone for treating MLL rearranged AML patients. Patients treated with Allo-HSCT have a better prognosis and a longer survival. CR is an independent prognostic factor for OS, and extramedullary involvement is an independent prognostic factor for DFS. MLL rearranged AML patients with thrombocytopenia at onset <50×109 had very bad OS and DFS. PMID:27373985

  15. Therapy-related acute myeloid leukemia with eosinophilia, basophilia, t(4;14)(q12;q24) and PDGFRA rearrangement: a case report and review of the literature

    OpenAIRE

    Zhou, Jun; Papenhausen, Peter; Shao, Haipeng

    2015-01-01

    The myeloid and lymphoid neoplasms with eosinophilia and PDGFRA gene rearrangements usually show a good response to Imatinib and are typically associated with a normal karyotype, occasionally exhibiting a secondary chromosomal abnormality associated with clonal evolution. Five variant translocations involving PDGFRA have been reported. Here, we report a rare case of therapy-related acute myeloid leukemia with PDGFRA rearrangement after chemotherapy for prior B lymphoblastic leukemia (B-ALL). ...

  16. Split hand/split foot malformation, deafness, and mental retardation with a complex cytogenetic rearrangement involving 7q21.3.

    OpenAIRE

    Ignatius, J.; Knuutila, S; Scherer, S W; Trask, B; Kere, J

    1996-01-01

    Split hand/split foot malformation (SHSF) has been described in several patients associated with cytogenetically visible rearrangements involving chromosome 7q. Characterisation of these patients has led to localisation of an autosomal dominant form of SHSF to 7q21-22; the locus has been designated SHFM1. We describe a patient with a complex, apparently balanced cytogenetic rearrangement, including a translocation breakpoint at 7q21.3 near the DSS1 gene. In addition to ectrodactyly of all fou...

  17. Recurrent DNA inversion rearrangements in the human genome

    DEFF Research Database (Denmark)

    Flores, Margarita; Morales, Lucía; Gonzaga-Jauregui, Claudia;

    2007-01-01

    Several lines of evidence suggest that reiterated sequences in the human genome are targets for nonallelic homologous recombination (NAHR), which facilitates genomic rearrangements. We have used a PCR-based approach to identify breakpoint regions of rearranged structures in the human genome...

  18. Symmetric Rearrangements Around Infinity with Applications to Levy Processes

    CERN Document Server

    Drewitz, Alexander; Sun, Rongfeng

    2011-01-01

    We prove a new rearrangement inequality for multiple integrals, which partly generalizes a result of Friedberg and Luttinger (1976) and can be interpreted as involving symmetric rearrangements of domains around infinity. As applications, we prove two comparison results for general Levy processes and their symmetric rearrangements. The first application concerns the survival probability of a point particle in a Poisson field of moving traps following independent Levy motions. We show that the survival probability can only increase if the point particle does not move, and the traps and the Levy motions are symmetrically rearranged. This essentially generalizes an isoperimetric inequality of Peres and Sousi (2011) for the Wiener sausage. In the second application, we show that the q-capacity of a Borel measurable set for a Levy process can only increase if the set and the Levy process are symmetrically rearranged. This result generalizes an inequality obtained by Watanabe (1983) for symmetric Levy processes.

  19. Catalytic rearrangement of the chloroallyl ethers of p-cresol

    International Nuclear Information System (INIS)

    The rearrangement of a series of p-cresol ethers (β- and γ-chloro-, βγ- and βγ,γ-trichloroallyl), catalyzed by boron trifluoride etherate, was studied. Increase in the number of chlorine atoms in the allyl unit of the ether hinders the rearrangement, and its mechanism changes in the investigated series of ethers from intramolecular [3,3]-sigmatropic (with inversion of the allyl unit) to intermolecular, which corresponds to electrophilic substitution in the aromatic ring (without inversion). The presence of the chlorine atom at the β position of the allyl unit promotes rearrangement by a concerted intramolecular mechanism, while a chlorine atom at the γ position promotes rearrangement by an intermolecular stage mechanism. Two chlorine atoms at the γ position give rise mainly to the intermolecular rearrangement path

  20. Anaplastic Lymphoma Kinase Rearrangement in Digestive Tract Cancer: Implication for Targeted Therapy in Chinese Population.

    Directory of Open Access Journals (Sweden)

    Jianming Ying

    Full Text Available Anaplastic lymphoma kinase (ALK rearrangements define a subgroup of lung cancer which is eligible to targeted kinase inhibition. The aim of this study is to observe the incidence rate of ALK fusion in a large cohort of Chinese digestive tract cancer patients.Tissue microarray (TMA was constructed from 808 digestive tract cancer cases, including 169 esophageal squamous cell carcinoma, 182 gastric cancer and 457 colorectal cancer (CRC cases. We tested all cases for ALK expression via a fully automated immunohistochemistry (IHC assay. The IHC-positive cases were subjected to fluorescence in situ hybridization (FISH, real-time polymerase chain reaction (qRT-PCR, target gene enrichment and sequencing for confirmation of ALK gene rearrangement and discovery of novel fusion partner.Among the tested cases, 2 (0.44% CRC cases showed positive both by IHC and FISH. By qRT-PCR, EML4-ALK fusion was found in one IHC-positive CRC case. In another IHC-positive CRC case, target gene enrichment and sequencing revealed ALK was fused to a novel partner, spectrin beta non-erythrocytic 1 (SPTBN1. One gastric cancer case showed partially positive IHC result, but no fusion was found by FISH and gene sequencing.The incidence rate of ALK gene fusion in Chinese CRC patients was 0.44%,but not detectable in gastric and esophageal cancers. The novel SPTBN1 -ALK fusion, together with other ALK fusion genes, may become a potential target for anti-ALK therapy.

  1. DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage.

    Science.gov (United States)

    Zody, Michael C; Garber, Manuel; Adams, David J; Sharpe, Ted; Harrow, Jennifer; Lupski, James R; Nicholson, Christine; Searle, Steven M; Wilming, Laurens; Young, Sarah K; Abouelleil, Amr; Allen, Nicole R; Bi, Weimin; Bloom, Toby; Borowsky, Mark L; Bugalter, Boris E; Butler, Jonathan; Chang, Jean L; Chen, Chao-Kung; Cook, April; Corum, Benjamin; Cuomo, Christina A; de Jong, Pieter J; DeCaprio, David; Dewar, Ken; FitzGerald, Michael; Gilbert, James; Gibson, Richard; Gnerre, Sante; Goldstein, Steven; Grafham, Darren V; Grocock, Russell; Hafez, Nabil; Hagopian, Daniel S; Hart, Elizabeth; Norman, Catherine Hosage; Humphray, Sean; Jaffe, David B; Jones, Matt; Kamal, Michael; Khodiyar, Varsha K; LaButti, Kurt; Laird, Gavin; Lehoczky, Jessica; Liu, Xiaohong; Lokyitsang, Tashi; Loveland, Jane; Lui, Annie; Macdonald, Pendexter; Major, John E; Matthews, Lucy; Mauceli, Evan; McCarroll, Steven A; Mihalev, Atanas H; Mudge, Jonathan; Nguyen, Cindy; Nicol, Robert; O'Leary, Sinéad B; Osoegawa, Kazutoyo; Schwartz, David C; Shaw-Smith, Charles; Stankiewicz, Pawel; Steward, Charles; Swarbreck, David; Venkataraman, Vijay; Whittaker, Charles A; Yang, Xiaoping; Zimmer, Andrew R; Bradley, Allan; Hubbard, Tim; Birren, Bruce W; Rogers, Jane; Lander, Eric S; Nusbaum, Chad

    2006-04-20

    Chromosome 17 is unusual among the human chromosomes in many respects. It is the largest human autosome with orthology to only a single mouse chromosome, mapping entirely to the distal half of mouse chromosome 11. Chromosome 17 is rich in protein-coding genes, having the second highest gene density in the genome. It is also enriched in segmental duplications, ranking third in density among the autosomes. Here we report a finished sequence for human chromosome 17, as well as a structural comparison with the finished sequence for mouse chromosome 11, the first finished mouse chromosome. Comparison of the orthologous regions reveals striking differences. In contrast to the typical pattern seen in mammalian evolution, the human sequence has undergone extensive intrachromosomal rearrangement, whereas the mouse sequence has been remarkably stable. Moreover, although the human sequence has a high density of segmental duplication, the mouse sequence has a very low density. Notably, these segmental duplications correspond closely to the sites of structural rearrangement, demonstrating a link between duplication and rearrangement. Examination of the main classes of duplicated segments provides insight into the dynamics underlying expansion of chromosome-specific, low-copy repeats in the human genome. PMID:16625196

  2. Context-based FISH localization of genomic rearrangements within chromosome 15q11.2q13 duplicons

    Directory of Open Access Journals (Sweden)

    Knoll Joan HM

    2011-08-01

    Full Text Available Abstract Background Segmental duplicons (SDs predispose to an increased frequency of chromosomal rearrangements. These rearrangements can cause a diverse range of phenotypes due to haploinsufficiency, in cis positional effects or gene interruption. Genomic microarray analysis has revealed gene dosage changes adjacent to duplicons, but the high degree of similarity between duplicon sequences has confounded unequivocal assignment of chromosome breakpoints within these intervals. In this study, we localize rearrangements within duplicon-enriched regions of Angelman/Prader-Willi (AS/PWS syndrome chromosomal deletions with fluorescence in situ hybridization (FISH. Results Breakage intervals in AS deletions were localized recursively with short, coordinate-defined, single copy (SC and low copy (LC genomic FISH probes. These probes were initially coincident with duplicons and regions of previously reported breakage in AS/PWS. Subsequently, probes developed from adjacent genomic intervals more precisely delineated deletion breakage intervals involving genes, pseudogenes and duplicons in 15q11.2q13. The observed variability in the deletion boundaries within previously described Class I and Class II deletion AS samples is related to the local genomic architecture in this chromosomal region. Conclusions Chromosome 15 abnormalities associated with SDs were precisely delineated at a resolution equivalent to genomic Southern analysis. This context-dependent approach can define the boundaries of chromosome rearrangements for other genomic disorders associated with SDs.

  3. Cinteny: flexible analysis and visualization of synteny and genome rearrangements in multiple organisms

    Directory of Open Access Journals (Sweden)

    Meller Jaroslaw

    2007-03-01

    Full Text Available Abstract Background Identifying syntenic regions, i.e., blocks of genes or other markers with evolutionary conserved order, and quantifying evolutionary relatedness between genomes in terms of chromosomal rearrangements is one of the central goals in comparative genomics. However, the analysis of synteny and the resulting assessment of genome rearrangements are sensitive to the choice of a number of arbitrary parameters that affect the detection of synteny blocks. In particular, the choice of a set of markers and the effect of different aggregation strategies, which enable coarse graining of synteny blocks and exclusion of micro-rearrangements, need to be assessed. Therefore, existing tools and resources that facilitate identification, visualization and analysis of synteny need to be further improved to provide a flexible platform for such analysis, especially in the context of multiple genomes. Results We present a new tool, Cinteny, for fast identification and analysis of synteny with different sets of markers and various levels of coarse graining of syntenic blocks. Using Hannenhalli-Pevzner approach and its extensions, Cinteny also enables interactive determination of evolutionary relationships between genomes in terms of the number of rearrangements (the reversal distance. In particular, Cinteny provides: i integration of synteny browsing with assessment of evolutionary distances for multiple genomes; ii flexibility to adjust the parameters and re-compute the results on-the-fly; iii ability to work with user provided data, such as orthologous genes, sequence tags or other conserved markers. In addition, Cinteny provides many annotated mammalian, invertebrate and fungal genomes that are pre-loaded and available for analysis at http://cinteny.cchmc.org. Conclusion Cinteny allows one to automatically compare multiple genomes and perform sensitivity analysis for synteny block detection and for the subsequent computation of reversal distances

  4. Clinicopathologic characteristics andtherapeutic responses ofChinese patients withnon-small cell lung cancer who harbor an anaplastic lymphoma kinase rearrangement

    Institute of Scientific and Technical Information of China (English)

    ShaFu; HaiYunWang; FangWang; MaYanHuang; LingDeng; XiaoZhang; ZuLuYe; JianYong Shao

    2015-01-01

    Introduction:The rearrangement of the anaplastic lymphoma kinase (ALK) gene accounts for approximately 1%–6%of lung adenocarcinoma cases and deifnes a molecular subgroup of tumors characterized by clinical sensitivity toALK inhibitors such as crizotinib. This study aimed to identify the relationship betweenALK rearrangement and the clinico‑pathologic characteristics of non‑small cell lung cancer (NSCLC) and to analyze the therapeutic responses of crizotinib and conventional chemotherapy toALK rearrangement in NSCLC patients. Methods:A total of 487 lung cancer patients who underwent testing forALK rearrangement in our department were included in this study.ALK rearrangement was examined by using lfuorescence insitu hybridization (FISH) assay. Results:Among the 487 patients, 44 (9.0%) were diagnosed withALK rearrangement by using FISH assay. In 123 patients with adenocarcinoma who were non‑smokers and of a young age (≤58years old), the frequency ofALK rearrangement was 20.3% (25/123). Short overall survival (OS) was associated with non‑adenocarcinoma tumor type (P=0.006), poorly differentiated tumors (P=0.001), advanced‑stage tumors (P<0.001), smoking history (P=0.008), and wild‑type epidermal growth factor receptor (EGFR) (P=0.008). Moreover, patients with poorly differentiated and advanced‑stage tumors had a shorter time to cancer progression compared with those with well differentiated (P=0.023) and early‑stage tumors (P=0.001), respectively. Conclusions:ALK‑rearranged NSCLC tends to occur in younger individuals who are either non‑smokers or light smokers with adenocarcinoma. Patients withALK rearrangement might beneift fromALK inhibitor therapy.

  5. TPR-MET oncogenic rearrangement: Detection by polymerase chain reaction amplification of the transcript and expression in human tumor cells lines

    International Nuclear Information System (INIS)

    Activation of the MET protooncogene by a rearrangement involving the fusion of TPR and MET specific gene sequences has been observed in a human osteosarcoma cell line (HOS) treated in vitro with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). No information has been available about the possible occurrence of this rearrangement in human tumors. To facilitate rapid screening of human cell lines and tumor samples for this specific gene rearrangement; the authors developed a sensitive detection method based on polymerase chain reaction (PCR) amplification of TPR-MET mRNA. cDNA was generated from cellular transcripts by using one of the PCR primers, which was then used as a template for PCR amplification of a 205-base-pair region carrying the breakpoint. An end-labeled internal probe was hybridized in solution to an aliquot of the PCR product for detecting amplification. Cells could be directly screened by the assay without prior isolation of RNA. A 205-base-pair DNA fragment characteristic of the TRP-MET rearrangement was detected in cell lines previously known to contain this altered sequence. The rearrangement was also detected at very low levels in the parental (nontransformed) cell line, HOS TE-85. A preliminary survey of cell lines derived from a variety of human tumors indicates that TPR-MET rearrangement occurred and was expressed at very low frequencies by cells from 7 of 14 tumors of nonhematopoietic origin

  6. Deletional rearrangement in the human T-cell receptor α-chain locus

    International Nuclear Information System (INIS)

    The antigen-specific receptor on the surface of mature T lymphocytes is a heterodimer consisting of polypeptides termed α and β. In the course of characterizing human T-cell tumors with an immature (CD4-, CD8-) surface phenotype, the authors detected a 2-kilobase α-related transcript. Analysis of cDNA clones corresponding to this transcript established that a genetic element (which they call TEA, for T early α) located between the α-chain variable- and joining-region genes had been spliced to the α constant region. The TEA transcript is present early in thymocyte ontogeny, and its expression declines during T-cell maturation. More important, the TEA area functions as an active site for rearrangement within the α gene locus. Blot hybridization of restriction enzyme-digested DNA with a TEA probe revealed a narrowly limited pattern of rearrangement in polyclonal thymic DNA, surprisingly different from the pattern expected for the mature α gene with its complex diversity. These DNA blots also showed that TEA is generally present in the germ-line configuration in cells expressing the γδ heterodimeric receptor and is deleted from mature (αβ-expressing) T-lymphocyte tumors and lines. Moreover, the TEA transcript lacked a long open reading frame for protein but instead possessed multiple copies of a repetitive element resembling those utilized in the heavy-chain class switch of the immunoglobulin genes. The temporal nature of the rearrangements and expression detected by TEA suggests that this recombination could mediate a transition between immature (γδ-expressing) T cells and mature (αβ-expressing) T cells

  7. Deletional rearrangement in the human T-cell receptor. cap alpha. -chain locus

    Energy Technology Data Exchange (ETDEWEB)

    de Villartay, J.P.; Lewis, D.; Hockett, R.; Waldmann, T.A.; Korsmeyer, S.J.; Cohen, D.I.

    1987-12-01

    The antigen-specific receptor on the surface of mature T lymphocytes is a heterodimer consisting of polypeptides termed ..cap alpha.. and ..beta... In the course of characterizing human T-cell tumors with an immature (CD4/sup -/, CD8/sup -/) surface phenotype, the authors detected a 2-kilobase ..cap alpha..-related transcript. Analysis of cDNA clones corresponding to this transcript established that a genetic element (which they call TEA, for T early ..cap alpha..) located between the ..cap alpha..-chain variable- and joining-region genes had been spliced to the ..cap alpha.. constant region. The TEA transcript is present early in thymocyte ontogeny, and its expression declines during T-cell maturation. More important, the TEA area functions as an active site for rearrangement within the ..cap alpha.. gene locus. Blot hybridization of restriction enzyme-digested DNA with a TEA probe revealed a narrowly limited pattern of rearrangement in polyclonal thymic DNA, surprisingly different from the pattern expected for the mature ..cap alpha.. gene with its complex diversity. These DNA blots also showed that TEA is generally present in the germ-line configuration in cells expressing the ..gamma..delta heterodimeric receptor and is deleted from mature (..cap alpha beta..-expressing) T-lymphocyte tumors and lines. Moreover, the TEA transcript lacked a long open reading frame for protein but instead possessed multiple copies of a repetitive element resembling those utilized in the heavy-chain class switch of the immunoglobulin genes. The temporal nature of the rearrangements and expression detected by TEA suggests that this recombination could mediate a transition between immature (..gamma..delta-expressing) T cells and mature (..cap alpha beta..-expressing) T cells.

  8. Definition of MYC genetic heteroclonality in diffuse large B-cell lymphoma with 8q24 rearrangement and its impact on protein expression.

    Science.gov (United States)

    Valera, Alexandra; Epistolio, Samantha; Colomo, Lluis; Riva, Alice; Balagué, Olga; Dlouhy, Ivan; Tzankov, Alexandar; Bühler, Marco; Haralambieva, Eugenia; Campo, Elias; Soldini, Davide; Mazzucchelli, Luca; Martin, Vittoria

    2016-08-01

    MYC rearrangement can be detected in a subgroup of diffuse large B-cell lymphoma characterized by unfavorable prognosis. In contrast to Burkitt lymphoma, the correlation between MYC rearrangement and MYC protein expression in diffuse large B-cell lymphoma is less clear, as approximately one-third of rearranged cases show negative or low expression by immunohistochemistry. To better understand whether specific characteristics of the MYC rearrangement may influence its protein expression, we investigated 43 de novo diffuse large B-cell lymphoma positive for 8q24 rearrangement by FISH, using 14 Burkitt lymphoma for comparison. Different cell populations (clones), breakpoints (classical vs non-classical FISH patterns), partner genes (IGH vs non-IGH) and immunostaining were detected and analyzed using computerized image systems. In a subgroup of diffuse large B-cell lymphoma, we observed different clones within the same tumor distinguishing the founder clone with MYC rearrangement alone from other subclones, carrying MYC rearrangement coupled with loss/extra copies of derivatives/normal alleles. This picture, which we defined MYC genetic heteroclonality, was found in 42% of cases and correlated to negative MYC expression (P=0.026). Non-classical FISH breakpoints were detected in 16% of diffuse large B-cell lymphoma without affecting expression (P=0.040). Non-IGH gene was the preferential partner of rearrangement in those diffuse large B-cell lymphoma showing MYC heteroclonality (P=0.016) and/or non-classical FISH breakpoints (P=0.058). MYC heteroclonality was not observed in Burkitt lymphoma and all cases had positive MYC expression. Non-classical FISH MYC breakpoint and non-IGH partner were found in 29 and 20% of Burkitt lymphoma, respectively. In conclusion, MYC genetic heteroclonality is a frequent event in diffuse large B-cell lymphoma and may have a relevant role in modulating MYC expression. PMID:27125356

  9. Selenium-Mediated Synthesis of Tetrasubstituted Naphthalenes through Rearrangement

    OpenAIRE

    James Tancock; Thomas Wirth

    2015-01-01

    New β-keto ester substituted stilbene derivatives have been synthesized and cyclized with selenium electrophiles in the presence of Lewis acids. This now allows access to 1,2,3,4-tetrasubstituted naphthalene derivatives as cyclization and rearrangement products.

  10. Expanding the clinical spectrum of the 16p11.2 chromosomal rearrangements: three patients with syringomyelia.

    Science.gov (United States)

    Schaaf, Christian P; Goin-Kochel, Robin P; Nowell, Kerri P; Hunter, Jill V; Aleck, Kirk A; Cox, Sarah; Patel, Ankita; Bacino, Carlos A; Shinawi, Marwan

    2011-02-01

    16p11.2 rearrangements are associated with developmental delay, cognitive impairment, autism spectrum disorder, behavioral problems (especially attention-deficit hyperactivity disorder), seizures, obesity, dysmorphic features, and abnormal head size. In addition, congenital anomalies and abnormal brain findings were frequently observed in patients with these rearrangements. We identified and performed a detailed microarray, phenotypic, and radiological characterization of three new patients with 16p11.2 rearrangements: two deletion patients and one patient with the reciprocal duplication. All patients have a heterozygous loss (deletion) or gain (duplication) corresponding to chromosomal coordinates (chr16: 29 528 190-30 107 184) with a minimal size of 579 kb. The deletion patients had language delay and learning disabilities and one met criteria for pervasive developmental disorder not otherwise specified. The duplication patient received a diagnosis of autism and had academic deficits and behavioral problems. The patients with deletion had long cervicothoracic syringomyelia and the duplication patient had long thoracolumbar syringomyelia. The syringomyelia in one patient with deletion was associated with Chiari malformation. Our findings highlight the broad spectrum of clinical and neurological manifestations in patients with 16p11.2 rearrangements. Our observation suggests that genes (or a single gene) within the implicated interval have significant roles in the pathogenesis of syringomyelia. A more comprehensive and systematic research is warranted to study the frequency and spectrum of malformations in the central nervous system in these patients.

  11. Genome-wide sequencing for the identification of rearrangements associated with Tourette syndrome and obsessive-compulsive disorder

    Directory of Open Access Journals (Sweden)

    Hooper Sean D

    2012-12-01

    Full Text Available Abstract Background Tourette Syndrome (TS is a neuropsychiatric disorder in children characterized by motor and verbal tics. Although several genes have been suggested in the etiology of TS, the genetic mechanisms remain poorly understood. Methods Using cytogenetics and FISH analysis, we identified an apparently balanced t(6,22(q16.2;p13 in a male patient with TS and obsessive-compulsive disorder (OCD. In order to map the breakpoints and to identify additional submicroscopic rearrangements, we performed whole genome mate-pair sequencing and CGH-array analysis on DNA from the proband. Results Sequence and CGH array analysis revealed a 400 kb deletion located 1.3 Mb telomeric of the chromosome 6q breakpoint, which has not been reported in controls. The deletion affects three genes (GPR63, NDUFA4 and KLHL32 and overlaps a region previously found deleted in a girl with autistic features and speech delay. The proband’s mother, also a carrier of the translocation, was diagnosed with OCD and shares the deletion. We also describe a further potentially related rearrangement which, while unmapped in Homo sapiens, was consistent with the chimpanzee genome. Conclusions We conclude that genome-wide sequencing at relatively low resolution can be used for the identification of submicroscopic rearrangements. We also show that large rearrangements may escape detection using standard analysis of whole genome sequencing data. Our findings further provide a candidate region for TS and OCD on chromosome 6q16.

  12. Simple and Rapid In Vivo Generation of Chromosomal Rearrangements using CRISPR/Cas9 Technology

    Directory of Open Access Journals (Sweden)

    Rafael B. Blasco

    2014-11-01

    Full Text Available Generation of genetically engineered mouse models (GEMMs for chromosomal translocations in the endogenous loci by a knockin strategy is lengthy and costly. The CRISPR/Cas9 system provides an innovative and flexible approach for genome engineering of genomic loci in vitro and in vivo. Here, we report the use of the CRISPR/Cas9 system for engineering a specific chromosomal translocation in adult mice in vivo. We designed CRISPR/Cas9 lentiviral vectors to induce cleavage of the murine endogenous Eml4 and Alk loci in order to generate the Eml4-Alk gene rearrangement recurrently found in non-small-cell lung cancers (NSCLCs. Intratracheal or intrapulmonary inoculation of lentiviruses induced Eml4-Alk gene rearrangement in lung cells in vivo. Genomic and mRNA sequencing confirmed the genome editing and the production of the Eml4-Alk fusion transcript. All mice developed Eml4-Alk-rearranged lung tumors 2 months after the inoculation, demonstrating that the CRISPR/Cas9 system is a feasible and simple method for the generation of chromosomal rearrangements in vivo.

  13. Targeted genomic rearrangements using CRISPR/Cas technology

    OpenAIRE

    Choi, Peter S.; Meyerson, Matthew

    2014-01-01

    Genomic rearrangements are frequently observed in cancer cells but have been difficult to generate in a highly specific manner for functional analysis. Here we report the application of CRISPR/Cas technology to successfully generate several types of chromosomal rearrangements implicated as driver events in lung cancer, including the CD74-ROS1 translocation event and the EML4-ALK and KIF5B-RET inversion events. Our results demonstrate that Cas9-induced DNA breaks promote efficient rearrangemen...

  14. Mechanisms of chromosomal rearrangement in the human genome

    OpenAIRE

    Lieber Michael R; Tsai Albert G

    2010-01-01

    Abstract Many human cancers are associated with characteristic chromosomal rearrangements, especially hematopoietic cancers such as leukemias and lymphomas. The first and most critical step in the rearrangement process is the induction of two DNA double-strand breaks (DSB). In all cases, at least one of the two DSBs is generated by a pathologic process, such as (1) randomly-positioned breaks due to ionizing radiation, free radical oxidative damage, or spontaneous hydrolysis; (2) breaks associ...

  15. Monotone equimeasurable rearrangements with non-additive probabilities

    OpenAIRE

    Ghossoub, Mario

    2011-01-01

    In the classical theory of monotone equimeasurable rearrangements of functions, “equimeasurability” (i.e. the fact the two functions have the same distribution) is defined relative to a given additive probability measure. These rearrangement tools have been successfully used in many problems in economic theory dealing with uncertainty where the monotonicity of a solution is desired. However, in all of these problems, uncertainty refers to the classical Bayesian understanding of the term, wher...

  16. The effects of graded levels of calorie restriction: VII. Topological rearrangement of hypothalamic aging networks.

    Science.gov (United States)

    Derous, Davina; Mitchell, Sharon E; Green, Cara L; Wang, Yingchun; Han, Jing Dong J; Chen, Luonan; Promislow, Daniel E L; Lusseau, David; Speakman, John R; Douglas, Alex

    2016-05-01

    Connectivity in a gene-gene network declines with age, typically within gene clusters. We explored the effect of short-term (3 months) graded calorie restriction (CR) (up to 40 %) on network structure of aging-associated genes in the murine hypothalamus by using conditional mutual information. The networks showed a topological rearrangement when exposed to graded CR with a higher relative within cluster connectivity at 40CR. We observed changes in gene centrality concordant with changes in CR level, with Ppargc1a, and Ppt1 having increased centrality and Etfdh, Traf3 and Abcc1 decreased centrality as CR increased. This change in gene centrality in a graded manner with CR, occurred in the absence of parallel changes in gene expression levels. This study emphasizes the importance of augmenting traditional differential gene expression analyses to better understand structural changes in the transcriptome. Overall our results suggested that CR induced changes in centrality of biological relevant genes that play an important role in preventing the age-associated loss of network integrity irrespective of their gene expression levels. PMID:27115072

  17. Myeloid neoplasm with prominent eosinophilia and PDGFRA rearrangement treated with imatinib mesylate

    DEFF Research Database (Denmark)

    Rathe, Mathias; Kielsgaard Kristensen, Thomas; Møller, Michael Boe;

    2010-01-01

    The FIP1L1-PDGFRA fusion gene is the most frequent genetic aberration in myeloid neoplasms associated with eosinophilia and abnormalities of PDGFRA, PDGFRB, or FGFR1. Affected patients in adult populations are very sensitive to imatinib therapy. Pediatric cases are rare and so far only one case of...... FIP1L1-PDGFRA positive disease has been reported. We report a 2-year-old female with a myeloid neoplasm associated with eosinophilia and rearrangement of PDGFRA. Treatment with imatinib resulted in complete and durable clinical, hematological, and molecular remission within 3 months after starting...

  18. Widespread rearrangement of 3D chromatin organization underlies polycomb-mediated stress-induced silencing.

    Science.gov (United States)

    Li, Li; Lyu, Xiaowen; Hou, Chunhui; Takenaka, Naomi; Nguyen, Huy Q; Ong, Chin-Tong; Cubeñas-Potts, Caelin; Hu, Ming; Lei, Elissa P; Bosco, Giovanni; Qin, Zhaohui S; Corces, Victor G

    2015-04-16

    Chromosomes of metazoan organisms are partitioned in the interphase nucleus into discrete topologically associating domains (TADs). Borders between TADs are formed in regions containing active genes and clusters of architectural protein binding sites. The transcription of most genes is repressed after temperature stress in Drosophila. Here we show that temperature stress induces relocalization of architectural proteins from TAD borders to inside TADs, and this is accompanied by a dramatic rearrangement in the 3D organization of the nucleus. TAD border strength declines, allowing for an increase in long-distance inter-TAD interactions. Similar but quantitatively weaker effects are observed upon inhibition of transcription or depletion of individual architectural proteins. Heat shock-induced inter-TAD interactions result in increased contacts among enhancers and promoters of silenced genes, which recruit Pc and form Pc bodies in the nucleolus. These results suggest that the TAD organization of metazoan genomes is plastic and can be reconfigured quickly. PMID:25818644

  19. Detection of EML4-ALK gene rearrangement in NSCLC by Ventana IHC and the challenges for diagnosis%Ventana免疫组化检测非小细胞肺癌EML4-ALK融合基因及其结果判读难点分析

    Institute of Scientific and Technical Information of China (English)

    王璇; 余波; 马恒辉; 周晓军; 石群立; 宋勇; 王建东

    2015-01-01

    目的:分析Ventana免疫组织化学染色( IHC)检测非小细胞肺癌( NSCLC)组织中EML4⁃ALK融合基因的突变情况。解析Ventana IHC结果判读的难点和陷阱,为此项检测的开展提供参考。方法回顾性分析695份Ventana IHC检测NSCLC标本,对部分标本进行了实时定量PCR( qRT⁃PCR)对照研究。结果 EML4⁃ALK在腺癌中的突变率为8�78%,鳞状细胞癌中的突变率为4�49%,总突变率为8�48%。10例Ventana IHC为(-)和(+)标本qRT⁃PCR检测为阴性;5例Ventana IHC染色(+++)标本qRT⁃PCR检测均为阳性;5例Ventana IHC(++)标本qRT⁃PCR检测1例阳性。结论 EML4⁃ALK融合基因主要发生在肺腺癌。 Ventana IHC检测结果存在判读难点和陷阱,判读需要谨慎。 EML4⁃ALK IHC检测阳性(++)的需要qRT⁃PCR或其它方法进一步证实。%Objective To analyze the occurrence of EML4⁃ALK gene rearrangement in non⁃small cell lung cancer ( NSCLC) detected by Ventana immunohistochemical staining (IHC), as to explore the challenges of Ventana IHC and provide a reference for other hospital to carry out the examination. Methods In this study, 659 cases of NSCLC were retrospectively analyzed and part of samples were checked by qRT⁃PCR. Results The occurrence rate of EML4⁃ALk in adenocarcinoma was 8�78% and in squamous cell carcinoma was 4�49%. Total occurrence in NSCLC was 8�48%. All cases with IHC staining (-) and (+) were confirmed negative mu⁃tation with qRT⁃PCR. Five cases with IHC staining (+++) were positive confirmed by qRT⁃PCR. One out of 5 cases with IHC staining (++) was confirmed positive by qRT⁃PCR. Conclusion EML4⁃ALK predominantly occurred in lung adenocarcinoma. There are some challenges in diagnosis of Ventana IHC. All cases with IHC staining (++) need to be verified by qRT⁃PCR or other methods.

  20. Cryptic genomic rearrangements in three patients with 46,XY disorders of sex development.

    Directory of Open Access Journals (Sweden)

    Maki Igarashi

    Full Text Available BACKGROUND: 46,XY disorders of sex development (46,XY DSD are genetically heterogeneous conditions. Recently, a few submicroscopic genomic rearrangements have been reported as novel genetic causes of 46,XY DSD. METHODOLOGY/PRINCIPAL FINDINGS: To clarify the role of cryptic rearrangements in the development of 46,XY DSD, we performed array-based comparative genomic hybridization analysis for 24 genetic males with genital abnormalities. Heterozygous submicroscopic deletions were identified in three cases (cases 1-3. A ∼8.5 Mb terminal deletion at 9p24.1-24.3 was detected in case 1 that presented with complete female-type external genitalia and mental retardation; a ∼2.0 Mb interstitial deletion at 20p13 was identified in case 2 with ambiguous external genitalia and short stature; and a ∼18.0 Mb interstitial deletion at 2q31.1-32 was found in case 3 with ambiguous external genitalia, mental retardation and multiple anomalies. The genital abnormalities of case 1 could be ascribed to gonadal dysgenesis caused by haploinsufficiency of DMRT1, while those of case 3 were possibly associated with perturbed organogenesis due to a deletion of the HOXD cluster. The deletion in case 2 affected 36 genes, none of which have been previously implicated in sex development. CONCLUSIONS/SIGNIFICANCE: The results indicate that cryptic genomic rearrangements constitute an important part of the molecular bases of 46,XY DSD and that submicroscopic deletions can lead to various types of 46,XY DSD that occur as components of contiguous gene deletion syndromes. Most importantly, our data provide a novel candidate locus for 46,XY DSD at 20p13.

  1. The genomic distribution of intraspecific and interspecific sequence divergence of human segmental duplications relative to human/chimpanzee chromosomal rearrangements

    OpenAIRE

    Eichler Evan E; She Xinwei; Cheng Ze; Marques-Bonet Tomàs; Navarro Arcadi

    2008-01-01

    Abstract Background It has been suggested that chromosomal rearrangements harbor the molecular footprint of the biological phenomena which they induce, in the form, for instance, of changes in the sequence divergence rates of linked genes. So far, all the studies of these potential associations have focused on the relationship between structural changes and the rates of evolution of single-copy DNA and have tried to exclude segmental duplications (SDs). This is paradoxical, since SDs are one ...

  2. Divergence of RNA polymerase α subunits in angiosperm plastid genomes is mediated by genomic rearrangement.

    Science.gov (United States)

    Blazier, J Chris; Ruhlman, Tracey A; Weng, Mao-Lun; Rehman, Sumaiyah K; Sabir, Jamal S M; Jansen, Robert K

    2016-01-01

    Genes for the plastid-encoded RNA polymerase (PEP) persist in the plastid genomes of all photosynthetic angiosperms. However, three unrelated lineages (Annonaceae, Passifloraceae and Geraniaceae) have been identified with unusually divergent open reading frames (ORFs) in the conserved region of rpoA, the gene encoding the PEP α subunit. We used sequence-based approaches to evaluate whether these genes retain function. Both gene sequences and complete plastid genome sequences were assembled and analyzed from each of the three angiosperm families. Multiple lines of evidence indicated that the rpoA sequences are likely functional despite retaining as low as 30% nucleotide sequence identity with rpoA genes from outgroups in the same angiosperm order. The ratio of non-synonymous to synonymous substitutions indicated that these genes are under purifying selection, and bioinformatic prediction of conserved domains indicated that functional domains are preserved. One of the lineages (Pelargonium, Geraniaceae) contains species with multiple rpoA-like ORFs that show evidence of ongoing inter-paralog gene conversion. The plastid genomes containing these divergent rpoA genes have experienced extensive structural rearrangement, including large expansions of the inverted repeat. We propose that illegitimate recombination, not positive selection, has driven the divergence of rpoA. PMID:27087667

  3. Divergence of RNA polymerase α subunits in angiosperm plastid genomes is mediated by genomic rearrangement

    Science.gov (United States)

    Blazier, J. Chris; Ruhlman, Tracey A.; Weng, Mao-Lun; Rehman, Sumaiyah K.; Sabir, Jamal S. M.; Jansen, Robert K.

    2016-01-01

    Genes for the plastid-encoded RNA polymerase (PEP) persist in the plastid genomes of all photosynthetic angiosperms. However, three unrelated lineages (Annonaceae, Passifloraceae and Geraniaceae) have been identified with unusually divergent open reading frames (ORFs) in the conserved region of rpoA, the gene encoding the PEP α subunit. We used sequence-based approaches to evaluate whether these genes retain function. Both gene sequences and complete plastid genome sequences were assembled and analyzed from each of the three angiosperm families. Multiple lines of evidence indicated that the rpoA sequences are likely functional despite retaining as low as 30% nucleotide sequence identity with rpoA genes from outgroups in the same angiosperm order. The ratio of non-synonymous to synonymous substitutions indicated that these genes are under purifying selection, and bioinformatic prediction of conserved domains indicated that functional domains are preserved. One of the lineages (Pelargonium, Geraniaceae) contains species with multiple rpoA-like ORFs that show evidence of ongoing inter-paralog gene conversion. The plastid genomes containing these divergent rpoA genes have experienced extensive structural rearrangement, including large expansions of the inverted repeat. We propose that illegitimate recombination, not positive selection, has driven the divergence of rpoA. PMID:27087667

  4. Genomic rearrangements of PTEN in prostate cancer

    Directory of Open Access Journals (Sweden)

    Sopheap ePhin

    2013-09-01

    Full Text Available The phosphatase and tensin homolog gene on chromosome 10q23.3 (PTEN is a negative regulator of the PIK3/Akt survival pathway and is the most frequently deleted tumor suppressor gene in prostate cancer. Monoallelic loss of PTEN is present in up to 60% of localized prostate cancers and complete loss of PTEN in prostate cancer is linked to metastasis and androgen independent progression. Studies on the genomic status of PTEN in prostate cancer initially used a two-color fluorescence in-situ hybridization (FISH assay for PTEN copy number detection in formalin fixed paraffin embedded tissue preparations. More recently, a four-color FISH assay containing two additional control probes flanking the PTEN locus with a lower false-positive rate was reported. Combined with the detection of other critical genomic biomarkers for prostate cancer such as ERG, AR, and MYC, the evaluation of PTEN genomic status has proven to be invaluable for patient stratification and management. Although less frequent than allelic deletions, point mutations in the gene and epigenetic silencing are also known to contribute to loss of PTEN function, and ultimately to prostate cancer initiation. Overall, it is clear that PTEN is a powerful biomarker for prostate cancer. Used as a companion diagnostic for emerging therapeutic drugs, FISH analysis of PTEN is promisingly moving human prostate cancer closer to more effective cancer management and therapies.

  5. Chromosome catastrophes involve replication mechanisms generating complex genomic rearrangements.

    Science.gov (United States)

    Liu, Pengfei; Erez, Ayelet; Nagamani, Sandesh C Sreenath; Dhar, Shweta U; Kołodziejska, Katarzyna E; Dharmadhikari, Avinash V; Cooper, M Lance; Wiszniewska, Joanna; Zhang, Feng; Withers, Marjorie A; Bacino, Carlos A; Campos-Acevedo, Luis Daniel; Delgado, Mauricio R; Freedenberg, Debra; Garnica, Adolfo; Grebe, Theresa A; Hernández-Almaguer, Dolores; Immken, LaDonna; Lalani, Seema R; McLean, Scott D; Northrup, Hope; Scaglia, Fernando; Strathearn, Lane; Trapane, Pamela; Kang, Sung-Hae L; Patel, Ankita; Cheung, Sau Wai; Hastings, P J; Stankiewicz, Paweł; Lupski, James R; Bi, Weimin

    2011-09-16

    Complex genomic rearrangements (CGRs) consisting of two or more breakpoint junctions have been observed in genomic disorders. Recently, a chromosome catastrophe phenomenon termed chromothripsis, in which numerous genomic rearrangements are apparently acquired in one single catastrophic event, was described in multiple cancers. Here, we show that constitutionally acquired CGRs share similarities with cancer chromothripsis. In the 17 CGR cases investigated, we observed localization and multiple copy number changes including deletions, duplications, and/or triplications, as well as extensive translocations and inversions. Genomic rearrangements involved varied in size and complexities; in one case, array comparative genomic hybridization revealed 18 copy number changes. Breakpoint sequencing identified characteristic features, including small templated insertions at breakpoints and microhomology at breakpoint junctions, which have been attributed to replicative processes. The resemblance between CGR and chromothripsis suggests similar mechanistic underpinnings. Such chromosome catastrophic events appear to reflect basic DNA metabolism operative throughout an organism's life cycle.

  6. Conditions for predicting quasistationary states by rearrangement formula

    Science.gov (United States)

    Yamaguchi, Yoshiyuki Y.; Ogawa, Shun

    2015-10-01

    Predicting the long-lasting quasistationary state for a given initial state is one of central issues in Hamiltonian systems having long-range interaction. A recently proposed method is based on the Vlasov description and uniformly redistributes the initial distribution along contours of the asymptotic effective Hamiltonian, which is defined by the obtained quasistationary state and is determined self-consistently. The method, to which we refer as the rearrangement formula, was suggested to give precise prediction under limited situations. Restricting initial states consisting of a spatially homogeneous part and small perturbation, we numerically reveal two conditions that the rearrangement formula prefers: One is a no Landau damping condition for the unperturbed homogeneous part, and the other comes from the Casimir invariants. Mechanisms of these conditions are discussed. Clarifying these conditions, we validate to use the rearrangement formula as the response theory for an external field, and we shed light on improving the theory as a nonequilibrium statistical mechanics.

  7. Low-Temperature Cationic Rearrangement in a Bulk Metal Oxide.

    Science.gov (United States)

    Li, Man-Rong; Retuerto, Maria; Stephens, Peter W; Croft, Mark; Sheptyakov, Denis; Pomjakushin, Vladimir; Deng, Zheng; Akamatsu, Hirofumi; Gopalan, Venkatraman; Sánchez-Benítez, Javier; Saouma, Felix O; Jang, Joon I; Walker, David; Greenblatt, Martha

    2016-08-16

    Cationic rearrangement is a compelling strategy for producing desirable physical properties by atomic-scale manipulation. However, activating ionic diffusion typically requires high temperature, and in some cases also high pressure in bulk oxide materials. Herein, we present the cationic rearrangement in bulk Mn2 FeMoO6 at unparalleled low temperatures of 150-300 (o) C. The irreversible ionic motion at ambient pressure, as evidenced by real-time powder synchrotron X-ray and neutron diffraction, and second harmonic generation, leads to a transition from a Ni3 TeO6 -type to an ordered-ilmenite structure, and dramatic changes of the electrical and magnetic properties. This work demonstrates a remarkable cationic rearrangement, with corresponding large changes in the physical properties in a bulk oxide at unprecedented low temperatures. PMID:27203790

  8. Progress of gene targeting in mouse

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Gene targeting is a powerful approach of study- ing the genefunction in vivo. Specific genetic modifications, including simple gene disruption, point mutations, large chromosomal deletions and rearrangements, targeted incor- poration of foreign genes, could be introduced into the mouse genome by gene targeting. Recent studies make it possible to do the gene targeting with temporal and spatial control.

  9. Isolation of germinal centerlike events from human spleen RNA. Somatic hypermutation of a clonally related VH6DJH rearrangement expressed with IgM, IgG, and IgA.

    OpenAIRE

    Varade, W S; Insel, R A

    1993-01-01

    12 rearranged human VH6 immunoglobulin heavy chain genes arising from the same rearrangement were isolated without preselection from the RNA of a fragment of human spleen. The 12 clones were isolated from a pool of 31 unique VH6 clones arising from 18 unique rearrangements. 2 of the 12 related clones were expressed with IgM, 2 with IgG, and 8 with IgA1. All the clones, including those expressing IgM, showed extensive somatic mutation of germline bases (5.6%), which was consistent with antigen...

  10. Submillisecond organic synthesis: Outpacing Fries rearrangement through microfluidic rapid mixing.

    Science.gov (United States)

    Kim, Heejin; Min, Kyoung-Ik; Inoue, Keita; Im, Do Jin; Kim, Dong-Pyo; Yoshida, Jun-ichi

    2016-05-01

    In chemical synthesis, rapid intramolecular rearrangements often foil attempts at site-selective bimolecular functionalization. We developed a microfluidic technique that outpaces the very rapid anionic Fries rearrangement to chemoselectively functionalize iodophenyl carbamates at the ortho position. Central to the technique is a chip microreactor of our design, which can deliver a reaction time in the submillisecond range even at cryogenic temperatures. The microreactor was applied to the synthesis of afesal, a bioactive molecule exhibiting anthelmintic activity, to demonstrate its potential for practical synthesis and production. PMID:27151864

  11. Submillisecond organic synthesis: Outpacing Fries rearrangement through microfluidic rapid mixing.

    Science.gov (United States)

    Kim, Heejin; Min, Kyoung-Ik; Inoue, Keita; Im, Do Jin; Kim, Dong-Pyo; Yoshida, Jun-ichi

    2016-05-01

    In chemical synthesis, rapid intramolecular rearrangements often foil attempts at site-selective bimolecular functionalization. We developed a microfluidic technique that outpaces the very rapid anionic Fries rearrangement to chemoselectively functionalize iodophenyl carbamates at the ortho position. Central to the technique is a chip microreactor of our design, which can deliver a reaction time in the submillisecond range even at cryogenic temperatures. The microreactor was applied to the synthesis of afesal, a bioactive molecule exhibiting anthelmintic activity, to demonstrate its potential for practical synthesis and production.

  12. Rearrangement of dypnones to 1,3,5-triarylbenzenes.

    Science.gov (United States)

    Deng, Kai; Huai, Qi-Yong; Shen, Zhi-Lun; Li, Hui-Jing; Liu, Chen; Wu, Yan-Chao

    2015-03-20

    Rearrangement of dypnones to 1,3,5-triarylbenzenes is described. The reaction is proposed to involve an aldol-type self-condensation of dypnones, followed by an intramolecular [2 + 2] cycloaddition and a retro-[2 + 2] cycloaddition. The reaction goes smoothly under obviously milder conditions in comparison to the cyclotrimerization of acetophenones to 1,3,5-triarylbenzenes (10 mol % of TsOH, 80 °C versus 130-148 °C). This unexpected rearrangement would provide new possible considerations in dypnone-involved organic synthesis. PMID:25740008

  13. Ultrafast infrared studies of complex ligand rearrangements in solution

    Energy Technology Data Exchange (ETDEWEB)

    Payne, Christine K.

    2003-05-31

    The complete description of a chemical reaction in solution depends upon an understanding of the reactive molecule as well as its interactions with the surrounding solvent molecules. Using ultrafast infrared spectroscopy it is possible to observe both the solute-solvent interactions and the rearrangement steps which determine the overall course of a chemical reaction. The topics addressed in these studies focus on reaction mechanisms which require the rearrangement of complex ligands and the spectroscopic techniques necessary for the determination of these mechanisms. Ligand rearrangement is studied by considering two different reaction mechanisms for which the rearrangement of a complex ligand constitutes the most important step of the reaction. The first system concerns the rearrangement of a cyclopentadienyl ring as the response of an organometallic complex to a loss of electron density. This mechanism, commonly referred to as ''ring slip'', is frequently cited to explain reaction mechanisms. However, the ring slipped intermediate is too short-lived to be observed using conventional methods. Using a combination of ultrafast infrared spectroscopy and electronic structure calculations it has been shown that the intermediate exists, but does not form an eighteen-electron intermediate as suggested by traditional molecular orbital models. The second example examines the initial steps of alkyne polymerization. Group 6 (Cr, Mo, W) pentacarbonyl species are generated photolytically and used to catalyze the polymerization of unsaturated hydrocarbons through a series of coordination and rearrangement steps. Observing this reaction on the femto- to millisecond timescale indicates that the initial coordination of an alkyne solvent molecule to the metal center results in a stable intermediate that does not rearrange to form the polymer precursor. This suggests that polymerization requires the dissociation of additional carbonyl ligands before

  14. Brueckner rearrangement energies in s-shell hypernuclei

    International Nuclear Information System (INIS)

    We consider rearrangement effects in light hypernuclei in the framework of the lowest order Brueckner theory. The energy change of the 4He core of Λ5He when the Λ hyperon is added to 4He is first estimated without much numerical computations. Next, rearrangement contributions in ΔΒΛΛ(ΛΛ6He) are estimated, which are important to deduce the strength of the ΛΛ interaction from the experimental ΔΒΛΛ(ΛΛ6He). (author)

  15. Cytogenetic, FISH and molecular characterization of 3q27/BCL-6 rearrangements in NHL

    Energy Technology Data Exchange (ETDEWEB)

    Wiodarska, I.; Styl, M.; Mecucci, C. [Univ. of Leuven (Belgium)] [and others

    1994-09-01

    Reciprocal translocations involving the chromosomal region 3q27 and one of the immunoglobulin loci at 14q32, 2p12 or 22q11 have been identified as the third most common type of chromosomal abnormality in Non Hodgkin`s lymphomas (NHLs), in addition to t(14;18) and t(8;14). These abnormalities appeared to be strongly associated with a diffuse, large cell subtype of B-cell NHL. Recently, a t(3;14) and t(3;22) have been cloned and a new transcriptional unit at 3q27, designated BCL-5, BCL-6 or LAZ3, has been identified. The gene appears to encode a new zinc finger protein with the putative function of a transcription factor. Rearrangements of the BCL-6 gene have been detected not only in cases with a typical t(3;14), t(2;3) and t(3;22), but also in a few NHL cases carrying 3q27 translocations not involving Ig genes. We report on nine B-NHL cases with a 3q27/BCL-6 rearrangement demonstrated by cytogenetic, FISH, and Southern analysis. Cytogenetic analysis complemented by FISH studies showed the presence of a classical t(3;14) or a t(3;22) in three cases and a variety of chromosomal aberrations involving the 3q27 locus in the remaining cases. Some of these translocations were not previously identified by conventional banding analysis. In three patients chromosome painting demonstrated involvement of both chromosome at the 3q24 band. We conclude: 3q27/BCL-6 rearrangements seem not to be restricted to diffuse large cell lymphoma. We here documented 3q27/BCL-6 abnormalities in Richter syndrome and follicular lymphomas. The variety of 3q27 aberrations at cytogenetic level suggests that, in addition to immunoglobulin genes, a number of other genes spreading over the human genome may deregulate BCL-6 in lymphomas. Chromosome painting is a powerful tool to demonstrate 3q27 abnormalities, not identified by conventional banding analysis.

  16. Density Functional Study on the Mechanism of Amadori Rearrangement Reaction

    Institute of Scientific and Technical Information of China (English)

    BAO Xiu-Xiu; CHEN Zu-Qin; XIE Hu-Jun

    2011-01-01

    The reaction mechanism of amadori rearrangement in the initial stage of Maillard reaction has been investigated by means of density functional theory calculations in the gaseous phase and aqueous solution. Cyclic ribose and glycine were taken as the model in the amadori rearrangement. Reaction mechanisms have been proposed, and possibility for the formation of different compounds has been evaluated through calculating the relative energy changes for different steps of the reaction by following the total mass balance. The calculations reveal that the amadori rearrangement initialized via the intramolecular rearrangement, transferring one proton from N(3) to O(4) atom. In the next step, the second proton is also transferred from N(3) to O(4) atom,corresponding to the cleavage of C(4)-O(4) bond and the release of one water molecule. Then another proton is transferred from N(3) to C(5) atom via TS3 with the reaction barrier of 58.3kcal.mol-1 after tunneling the effect correction calculated at the B3LYP/6-31+G(d) level of theory,and this step is rate limiting for the whole catalytic cycle. Ultimately, the product is generated via keto-enolic tautomerization. Present calculation could provide insights into the reaction mechanism of Maillard reaction since experimental evaluation of the role of intermediates in the Maillard reaction is quite complicated.

  17. λ-Rearrangements Characterization of Pringsheim Limit Points

    Directory of Open Access Journals (Sweden)

    Richard F. Patterson

    2007-01-01

    Full Text Available Sufficient conditions are given to assure that a four-dimensional matrix A will have the property that any double sequence x with finite P-limit point has- a λ-rearrangement z such that each finite P-limit point of x is a P-limit point of Az.

  18. Linear Secret Sharing Schemes and Rearrangements of Access Structures

    Institute of Scientific and Technical Information of China (English)

    Liang-liang Xiao; Mu-lan Liu

    2004-01-01

    In this paper we study linear secret sharing schemes by monotone span programs, according to the relation between realizing access structures by linear secret sharing schemes and computing monotone Boolean functions by monotone span programs. Weconstruct some linear secret sharing schemes. Furthermore, we study the rearrangements of access structures that is very important in practice.

  19. Beckmann rearrangement of ketoximes to lactams by triphosphazene catalyst.

    Science.gov (United States)

    Hashimoto, Masaharu; Obora, Yasushi; Sakaguchi, Satoshi; Ishii, Yasutaka

    2008-04-01

    Triphosphazene, 1,3,5-triazo-2,4,6-triphosphorine-2,2,4,4,6,6-chloride (TAPC), was found to be an efficient catalyst for the Beckmann rearrangement of cyclohexanone oxime and cyclododecanone oxime to epsilon-caprolactam and laurolactam, which are raw materials of nylon-6 and nylon-12, respectively.

  20. Lipschitz Properties in Variable Exponent Problems via Relative Rearrangement

    Institute of Scientific and Technical Information of China (English)

    Jean-Michel RAKOTOSON

    2010-01-01

    The author first studies the Lipschitz properties of the monotone and relative rearrangement mappings in variable exponent Lebesgue spaces completing the result given in[9].This paper is ended by establishing the Lipschitz properties for quasilinear problems with variable exponent when the right-hand side is in some dual spaces of a suitable Sobolev space associated to variable exponent.

  1. Clinical characteristics and outcomes of patients with primary lung adenocarcinoma harboring ALK rearrangements detected by FISH, IHC, and RT-PCR.

    Science.gov (United States)

    Wang, Jinghui; Cai, Yiran; Dong, Yujie; Nong, Jingying; Zhou, Lijuan; Liu, Guimei; Su, Dan; Li, Xi; Wu, Shafei; Chen, Xuejing; Qin, Na; Zeng, Xuan; Zhang, Haiqing; Zhang, Zongde; Zhang, Shucai

    2014-01-01

    EML4-ALK is a new driver gene of non-small cell lung cancer and a target of crizotinib. The objectives of this study were to determine the frequency of ALK rearrangements in a large cohort of patients with primary lung adenocarcinoma and to analyze the association of ALK rearrangements with clinicopathological characteristics and clinical outcomes. The roles of fluorescence in situ hybridization (FISH), Ventana immunohistochemistry (IHC), and reverse transcriptase polymerase chain reaction (RT-PCR) in the detection of ALK rearrangements were evaluated. The ALK rearrangement was detected in 430 specimens from individual patients with primary lung adenocarcinoma using FISH and Ventana IHC based on tissue microarrays. The EGFR status was detected in all of the specimens through DNA sequencing. An RT-PCR was performed on 200 of the specimens and confirmed by sequencing. Of the 430 patients, 46 (10.7%) harbored ALK rearrangements. The ALK rearrangements were associated with a younger age and the EGFR wild type in comparison with ALK-negative patients. The sensitivity and specificity of the Ventana IHC were 100% and 98.2%, respectively, and the concordance rate between the FISH and the Ventana IHC was 98.4%. The sensitivity and specificity of RT-PCR were 95.5% and 87.0%, respectively, and the concordance rate between the FISH and the RT-PCR was 89.0%. The Cox analysis indicated that an early stage and EGFR-activating mutations were independently associated with a longer OS. This study demonstrated that ALK rearrangements are associated with a younger age and the EGFR wild type rather than with other clinicopathological factors. Although the FISH and Ventana IHC have better concordance, and RT-PCR is a more sensitive method and can identify different variants or partners, the IHC and RT-PCR need to be further evaluated in clinical trials to identify their roles in guiding patients' targeted therapy using crizotinib.

  2. Clinical characteristics and outcomes of patients with primary lung adenocarcinoma harboring ALK rearrangements detected by FISH, IHC, and RT-PCR.

    Directory of Open Access Journals (Sweden)

    Jinghui Wang

    Full Text Available EML4-ALK is a new driver gene of non-small cell lung cancer and a target of crizotinib. The objectives of this study were to determine the frequency of ALK rearrangements in a large cohort of patients with primary lung adenocarcinoma and to analyze the association of ALK rearrangements with clinicopathological characteristics and clinical outcomes. The roles of fluorescence in situ hybridization (FISH, Ventana immunohistochemistry (IHC, and reverse transcriptase polymerase chain reaction (RT-PCR in the detection of ALK rearrangements were evaluated. The ALK rearrangement was detected in 430 specimens from individual patients with primary lung adenocarcinoma using FISH and Ventana IHC based on tissue microarrays. The EGFR status was detected in all of the specimens through DNA sequencing. An RT-PCR was performed on 200 of the specimens and confirmed by sequencing. Of the 430 patients, 46 (10.7% harbored ALK rearrangements. The ALK rearrangements were associated with a younger age and the EGFR wild type in comparison with ALK-negative patients. The sensitivity and specificity of the Ventana IHC were 100% and 98.2%, respectively, and the concordance rate between the FISH and the Ventana IHC was 98.4%. The sensitivity and specificity of RT-PCR were 95.5% and 87.0%, respectively, and the concordance rate between the FISH and the RT-PCR was 89.0%. The Cox analysis indicated that an early stage and EGFR-activating mutations were independently associated with a longer OS. This study demonstrated that ALK rearrangements are associated with a younger age and the EGFR wild type rather than with other clinicopathological factors. Although the FISH and Ventana IHC have better concordance, and RT-PCR is a more sensitive method and can identify different variants or partners, the IHC and RT-PCR need to be further evaluated in clinical trials to identify their roles in guiding patients' targeted therapy using crizotinib.

  3. Coexistence of minicircular and a highly rearranged mtDNA molecule suggests that recombination shapes mitochondrial genome organization.

    Science.gov (United States)

    Mao, Meng; Austin, Andrew D; Johnson, Norman F; Dowton, Mark

    2014-03-01

    Recombination has been proposed as a possible mechanism to explain mitochondrial (mt) gene rearrangements, although the issue of whether mtDNA recombination occurs in animals has been controversial. In this study, we sequenced the entire mt genome of the megaspilid wasp Conostigmus sp., which possessed a highly rearranged mt genome. The sequence of the A+T-rich region contained a number of different types of repeats, similar to those reported previously in the nematode Meloidogyne javanica, in which recombination was discovered. In Conostigmus, we detected the end products of recombination: a range of minicircles. However, using isolated (cloned) fragments of the A+T-rich region, we established that some of these minicircles were found to be polymerase chain reaction (PCR) artifacts. It appears that regions with repeats are prone to PCR template switching or PCR jumping. Nevertheless, there is strong evidence that one minicircle is real, as amplification primers that straddle the putative breakpoint junction produce a single strong amplicon from genomic DNA but not from the cloned A+T-rich region. The results provide support for the direct link between recombination and mt gene rearrangement. Furthermore, we developed a model of recombination which is important for our understanding of mtDNA evolution.

  4. The genomic distribution of intraspecific and interspecific sequence divergence of human segmental duplications relative to human/chimpanzee chromosomal rearrangements

    Directory of Open Access Journals (Sweden)

    Eichler Evan E

    2008-08-01

    Full Text Available Abstract Background It has been suggested that chromosomal rearrangements harbor the molecular footprint of the biological phenomena which they induce, in the form, for instance, of changes in the sequence divergence rates of linked genes. So far, all the studies of these potential associations have focused on the relationship between structural changes and the rates of evolution of single-copy DNA and have tried to exclude segmental duplications (SDs. This is paradoxical, since SDs are one of the primary forces driving the evolution of structure and function in our genomes and have been linked not only with novel genes acquiring new functions, but also with overall higher DNA sequence divergence and major chromosomal rearrangements. Results Here we take the opposite view and focus on SDs. We analyze several of the features of SDs, including the rates of intraspecific divergence between paralogous copies of human SDs and of interspecific divergence between human SDs and chimpanzee DNA. We study how divergence measures relate to chromosomal rearrangements, while considering other factors that affect evolutionary rates in single copy DNA. Conclusion We find that interspecific SD divergence behaves similarly to divergence of single-copy DNA. In contrast, old and recent paralogous copies of SDs do present different patterns of intraspecific divergence. Also, we show that some relatively recent SDs accumulate in regions that carry inversions in sister lineages.

  5. Molecular Characterization and Clinical Impact of TMPRSS2-ERG Rearrangement on Prostate Cancer: Comparison between FISH and RT-PCR

    Directory of Open Access Journals (Sweden)

    A. Fernández-Serra

    2013-01-01

    Full Text Available Prostate cancer (PCa is a very heterogeneous disease, and there are constraints in its current diagnosis. Serum PSA levels, digital rectal examination (DRE, and histopathologic analysis often drive to overdiagnosis and overtreatment. Since 2005, the presence of the genetic rearrangement between transmembrane-serine protease gene (TMPRSS2 and the erythroblast transformation-specific (ETS member ERG (v-ets erythroblastosis virus E26 oncogene homolog avian has been demonstrated in almost half of PCa cases. Both FISH and RT-PCR are useful tools for detecting these rearrangements, but very few comparatives between both techniques have been published. In this study, we included FFPE tumors from 294 PCa patients treated with radical prostatectomy with more than 5 years of followup. We constructed a total of 20 tissue microarrays in order to perform break-apart and tricolor probe FISH approaches that were compared with RT-PCR, showing a concordance of 80.6% (P<0.001. The presence of TMPRSS2-ERG rearrangement was observed in 56.6% of cases. No association between TMPRSS2-ERG status and clinicopathological parameters nor biochemical progression and clinical progression free survival was found. In conclusion, this study demonstrates that both FISH and RT-PCR are useful tools in the assessment of the TMPRSS2-ERG fusion gene status in PCa patients and that this genetic feature per se lacks prognostic value.

  6. SWI/SNF Subunits SMARCA4, SMARCD2 and DPF2 Collaborate in MLL-Rearranged Leukaemia Maintenance

    DEFF Research Database (Denmark)

    Cruickshank, V Adam; Sroczynska, Patrycja; Sankar, Aditya;

    2015-01-01

    tumour-suppressor function in many solid tumours; recently however, it has been reported to sustain leukaemogenic transformation in MLL-rearranged leukaemia in mice. Here we further explore the role of SMARCA4 and the two SWI/SNF subunits SMARCD2/BAF60B and DPF2/BAF45D in leukaemia. We observed the...... selective requirement for these proteins for leukaemic cell expansion and self-renewal in-vitro as well as in leukaemia. Gene expression profiling in human cells of each of these three factors suggests that they have overlapping functions in leukaemia. The gene expression changes induced by loss of the...

  7. Saucy-Marbet Rearrangements of Alkynyl Halides in the Synthesis of Highly Enantiomerically Enriched Allenyl Halides

    OpenAIRE

    Tang, Yu; Shen, Lichun; Dellaria, Becky J.; Richard P. Hsung

    2008-01-01

    A stereospecific Saucy-Marbet rearrangement of alkynyl halides is described here. These rearrangements provide an entry to highly enantiomerically enriched allenyl bromides and chlorides through excellent chirality transfer and the reservation of optical integrity of alkynyl halides.

  8. Genome sequencing of pediatric medulloblastoma links catastrophic DNA rearrangements with TP53 mutations

    DEFF Research Database (Denmark)

    Rausch, Tobias; Jones, David T W; Zapatka, Marc;

    2012-01-01

    Genomic rearrangements are thought to occur progressively during tumor development. Recent findings, however, suggest an alternative mechanism, involving massive chromosome rearrangements in a one-step catastrophic event termed chromothripsis. We report the whole-genome sequencing-based analysis ...

  9. Claisen, Cope and Related Rearrangements in the Synthesis of Flavour and Fragrance Compounds

    OpenAIRE

    Janusz Nowicki

    2000-01-01

    A review of the use of the Claisen, Cope and related [3,3]-sigmatropic rearrangements, sequential ("tandem") sigmatropic rearrangements and the "ene" reaction in the syntheses of flavour and fragrance compounds is presented.

  10. Ligand flexibility and framework rearrangement in a new family of porous metal-organic frameworks

    DEFF Research Database (Denmark)

    Hawxwell, Samuel M; Espallargas, Guillermo Mínguez; Bradshaw, Darren;

    2007-01-01

    Ligand flexibility permits framework rearrangement upon evacuation and gas uptake in a new family of porous MOFs.......Ligand flexibility permits framework rearrangement upon evacuation and gas uptake in a new family of porous MOFs....

  11. Id2 and E Proteins Orchestrate the Initiation and Maintenance of MLL-Rearranged Acute Myeloid Leukemia.

    Science.gov (United States)

    Ghisi, Margherita; Kats, Lev; Masson, Frederick; Li, Jason; Kratina, Tobias; Vidacs, Eva; Gilan, Omer; Doyle, Maria A; Newbold, Andrea; Bolden, Jessica E; Fairfax, Kirsten A; de Graaf, Carolyn A; Firth, Matthew; Zuber, Johannes; Dickins, Ross A; Corcoran, Lynn M; Dawson, Mark A; Belz, Gabrielle T; Johnstone, Ricky W

    2016-07-11

    E proteins and their antagonists, the Id proteins, are transcriptional regulators important for normal hematopoiesis. We found that Id2 acts as a key regulator of leukemia stem cell (LSC) potential in MLL-rearranged acute myeloid leukemia (AML). Low endogenous Id2 expression is associated with LSC enrichment while Id2 overexpression impairs MLL-AF9-leukemia initiation and growth. Importantly, MLL-AF9 itself controls the E-protein pathway by suppressing Id2 while directly activating E2-2 expression, and E2-2 depletion phenocopies Id2 overexpression in MLL-AF9-AML cells. Remarkably, Id2 tumor-suppressive function is conserved in t(8;21) AML. Low expression of Id2 and its associated gene signature are associated with poor prognosis in MLL-rearranged and t(8;21) AML patients, identifying the Id2/E-protein axis as a promising new therapeutic target in AML. PMID:27374225

  12. Complexity of genome evolution by segmental rearrangement in Brassica rapa revealed by sequence-level analysis

    Directory of Open Access Journals (Sweden)

    Paterson Andrew H

    2009-11-01

    Full Text Available Abstract Background The Brassica species, related to Arabidopsis thaliana, include an important group of crops and represent an excellent system for studying the evolutionary consequences of polyploidy. Previous studies have led to a proposed structure for an ancestral karyotype and models for the evolution of the B. rapa genome by triplication and segmental rearrangement, but these have not been validated at the sequence level. Results We developed computational tools to analyse the public collection of B. rapa BAC end sequence, in order to identify candidates for representing collinearity discontinuities between the genomes of B. rapa and A. thaliana. For each putative discontinuity, one of the BACs was sequenced and analysed for collinearity with the genome of A. thaliana. Additional BAC clones were identified and sequenced as part of ongoing efforts to sequence four chromosomes of B. rapa. Strikingly few of the 19 inter-chromosomal rearrangements corresponded to the set of collinearity discontinuities anticipated on the basis of previous studies. Our analyses revealed numerous instances of newly detected collinearity blocks. For B. rapa linkage group A8, we were able to develop a model for the derivation of the chromosome from the ancestral karyotype. We were also able to identify a rearrangement event in the ancestor of B. rapa that was not shared with the ancestor of A. thaliana, and is represented in triplicate in the B. rapa genome. In addition to inter-chromosomal rearrangements, we identified and analysed 32 BACs containing the end points of segmental inversion events. Conclusion Our results show that previous studies of segmental collinearity between the A. thaliana, Brassica and ancestral karyotype genomes, although very useful, represent over-simplifications of their true relationships. The presence of numerous cryptic collinear genome segments and the frequent occurrence of segmental inversions mean that inference of the positions

  13. Reproductive Incompatibility Involving Senegalese Aedes aegypti (L) Is Associated with Chromosome Rearrangements.

    Science.gov (United States)

    Dickson, Laura B; Sharakhova, Maria V; Timoshevskiy, Vladimir A; Fleming, Karen L; Caspary, Alex; Sylla, Massamba; Black, William C

    2016-04-01

    Aedes aegypti, the primary vector of dengue, yellow fever and Zika flaviviruses, consists of at least two subspecies. Aedes aegypti (Aaa) is light in color, has pale scales on the first abdominal tergite, oviposits in artificial containers, and preferentially feeds on humans. Aedes aegypti formosus (Aaf), has a dark cuticle, is restricted to sub-Saharan Africa, has no pale scales on the first abdominal tergite and frequently oviposits in natural containers. Scale patterns correlate with cuticle color in East Africa but not in Senegal, West Africa where black cuticle mosquitoes display a continuum of scaling patterns and breed domestically indoors. An earlier laboratory study did not indicate any pre- or postzygotic barriers to gene flow between Aaa and Aaf in East Africa. However, similar attempts to construct F1 intercross families between Aaa laboratory strains and Senegal Ae. aegypti (SenAae) failed due to poor F1 oviposition and low F2 egg-to-adult survival. Insemination and assortative mating experiments failed to identify prezygotic mating barriers. Backcrosses were performed to test for postzygotic isolation patterns consistent with Haldane's rule modified for species, like Aedes, that have an autosomal sex determining locus (SDL). Egg-pupal survival was predicted to be low in females mated to hybrid F1 males but average when a male mates with a hybrid F1 female. Survival was in fact significantly reduced when females mated to hybrid males but egg-pupal survival was significantly increased when males were mated to hybrid F1 females. These observations are therefore inconclusive with regards to Haldane's rule. Basic cytogenetic analyses and Fluorescent In Situ Hybridization (FISH) experiments were performed to compare SenAae strains with the IB12 strain of Aaa that was used for genome sequencing and physical mapping. Some SenAae strains had longer chromosomes than IB12 and significantly different centromeric indices on chromosomes 1 and 3. DAPI staining was

  14. Reproductive Incompatibility Involving Senegalese Aedes aegypti (L) Is Associated with Chromosome Rearrangements

    Science.gov (United States)

    Dickson, Laura B.; Sharakhova, Maria V.; Timoshevskiy, Vladimir A.; Fleming, Karen L.; Caspary, Alex; Sylla, Massamba; Black, William C.

    2016-01-01

    Aedes aegypti, the primary vector of dengue, yellow fever and Zika flaviviruses, consists of at least two subspecies. Aedes aegypti (Aaa) is light in color, has pale scales on the first abdominal tergite, oviposits in artificial containers, and preferentially feeds on humans. Aedes aegypti formosus (Aaf), has a dark cuticle, is restricted to sub-Saharan Africa, has no pale scales on the first abdominal tergite and frequently oviposits in natural containers. Scale patterns correlate with cuticle color in East Africa but not in Senegal, West Africa where black cuticle mosquitoes display a continuum of scaling patterns and breed domestically indoors. An earlier laboratory study did not indicate any pre- or postzygotic barriers to gene flow between Aaa and Aaf in East Africa. However, similar attempts to construct F1 intercross families between Aaa laboratory strains and Senegal Ae. aegypti (SenAae) failed due to poor F1 oviposition and low F2 egg-to-adult survival. Insemination and assortative mating experiments failed to identify prezygotic mating barriers. Backcrosses were performed to test for postzygotic isolation patterns consistent with Haldane’s rule modified for species, like Aedes, that have an autosomal sex determining locus (SDL). Egg-pupal survival was predicted to be low in females mated to hybrid F1 males but average when a male mates with a hybrid F1 female. Survival was in fact significantly reduced when females mated to hybrid males but egg-pupal survival was significantly increased when males were mated to hybrid F1 females. These observations are therefore inconclusive with regards to Haldane’s rule. Basic cytogenetic analyses and Fluorescent In Situ Hybridization (FISH) experiments were performed to compare SenAae strains with the IB12 strain of Aaa that was used for genome sequencing and physical mapping. Some SenAae strains had longer chromosomes than IB12 and significantly different centromeric indices on chromosomes 1 and 3. DAPI staining

  15. Reproductive Incompatibility Involving Senegalese Aedes aegypti (L) Is Associated with Chromosome Rearrangements.

    Science.gov (United States)

    Dickson, Laura B; Sharakhova, Maria V; Timoshevskiy, Vladimir A; Fleming, Karen L; Caspary, Alex; Sylla, Massamba; Black, William C

    2016-04-01

    Aedes aegypti, the primary vector of dengue, yellow fever and Zika flaviviruses, consists of at least two subspecies. Aedes aegypti (Aaa) is light in color, has pale scales on the first abdominal tergite, oviposits in artificial containers, and preferentially feeds on humans. Aedes aegypti formosus (Aaf), has a dark cuticle, is restricted to sub-Saharan Africa, has no pale scales on the first abdominal tergite and frequently oviposits in natural containers. Scale patterns correlate with cuticle color in East Africa but not in Senegal, West Africa where black cuticle mosquitoes display a continuum of scaling patterns and breed domestically indoors. An earlier laboratory study did not indicate any pre- or postzygotic barriers to gene flow between Aaa and Aaf in East Africa. However, similar attempts to construct F1 intercross families between Aaa laboratory strains and Senegal Ae. aegypti (SenAae) failed due to poor F1 oviposition and low F2 egg-to-adult survival. Insemination and assortative mating experiments failed to identify prezygotic mating barriers. Backcrosses were performed to test for postzygotic isolation patterns consistent with Haldane's rule modified for species, like Aedes, that have an autosomal sex determining locus (SDL). Egg-pupal survival was predicted to be low in females mated to hybrid F1 males but average when a male mates with a hybrid F1 female. Survival was in fact significantly reduced when females mated to hybrid males but egg-pupal survival was significantly increased when males were mated to hybrid F1 females. These observations are therefore inconclusive with regards to Haldane's rule. Basic cytogenetic analyses and Fluorescent In Situ Hybridization (FISH) experiments were performed to compare SenAae strains with the IB12 strain of Aaa that was used for genome sequencing and physical mapping. Some SenAae strains had longer chromosomes than IB12 and significantly different centromeric indices on chromosomes 1 and 3. DAPI staining was

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

    Science.gov (United States)

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

    2002-05-15

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

  17. Chromosome-specific staining to detect genetic rearrangements

    Science.gov (United States)

    Gray, Joe W.; Pinkel, Daniel; Tkachuk, Douglas; Westbrook, Carol

    2013-04-09

    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 analyzes. 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 and reagents are provided for the detection of genetic rearrangements. Probes and test kits are provided for use in detecting genetic rearrangements, particularly for use in tumor cytogenetics, in the detection of disease related loci, specifically cancer, such as chronic myelogenous leukemia (CML) and for biological dosimetry. Methods and reagents are described for cytogenetic research, for the differentiation of cytogenetically similar but genetically different diseases, and for many prognostic and diagnostic applications.

  18. Chromosome 12;15 rearrangements in patients with recurrent miscarriage

    Directory of Open Access Journals (Sweden)

    Nair S

    2006-01-01

    Full Text Available Background: An abnormal karyotype in either partner, especially featuring a translocation and/or inversion is considered to be a cause of recurrent miscarriages. It is generally assumed that recurrent miscarriage might be due to recurrent chromosomal abnormalities in the fetus due to a balanced aberration in one of the parents being inherited by the offspring in an unbalanced form. Aim: Evaluation of chromosomal rearrangements in couples with recurrent miscarriages. Materials and Methods: Peripheral blood was collected and lymphocyte cultures were set up. Slides prepared from the cell suspension were stained and screened for metaphases followed by karyotyping. Result: Balanced translocation was observed in the male partner in one case and in the female partners in the three other cases. Conclusion: Couples with recurrent miscarriage should be investigated for chromosomal rearrangements, thus helping in genetic counseling and providing the options for future pregnancies.

  19. Semiclassical asymptotic behavior and the rearrangement mechanisms for Coulomb particles

    Energy Technology Data Exchange (ETDEWEB)

    Bogdanov, A.V.; Gevorkyan, A.S.; Dubrovskii, G.V.

    1986-01-01

    The semiclassical asymptotic behavior of the eikonal amplitude of the resonance rearrangement in a system of three Coulomb particles is studied. It is shown that the general formula for the amplitude correctly describes two classical mechanisms (pickup and knockout) and one nonclassical mechanism (stripping). The classical mechanisms predominate at high energies, while the stripping mechanism predominates at lower energies. In the region of medium energies the dominant mechanism is the pickup (or Thomas) mechanism, which is realized by nonclassical means. For such transitions the classical cross section diverges, and the amplitude must be computed on a complex trajectory. The physical reasons for introducing the approximate complex trajectories are discussed. The contributions of all the mechanisms to the rearrangement cross section are found in their analytic forms.

  20. Recent applications of ring-rearrangement metathesis in organic synthesis.

    Science.gov (United States)

    Kotha, Sambasivarao; Meshram, Milind; Khedkar, Priti; Banerjee, Shaibal; Deodhar, Deepak

    2015-01-01

    Ring-rearrangement metathesis (RRM) involves multiple metathesis processes such as ring-opening metathesis (ROM)/ring-closing metathesis (RCM) in a one-pot operation to generate complex targets. RRM delivers complex frameworks that are difficult to assemble by conventional methods. The noteworthy point about this type of protocol is multi-bond formation and it is an atom economic process. In this review, we have covered literature that appeared during the last seven years (2008-2014). PMID:26664603

  1. Fries Rearrangement of Phenyl Acetate over Solid Acid Catalyst

    Institute of Scientific and Technical Information of China (English)

    CanXiongGUO; YanLIU; 等

    2002-01-01

    A silica-supported zirconium based solid acid (ZS) has been used as catalyst for the Fries rearrangement of phenyl acetate (PA). The catalyst showed a higher PA conversion activity and a much higher selectivity for o-hydroxyacetophenone (o-HAP) than for strongly acidic zeolite catalysts. The supported catalyst was characterized by XRD,IR,XPS,pyridine-TPD and the surface area measurements. The catalytic properties were influenced significantly by pretreatment temperature.

  2. Recent applications of ring-rearrangement metathesis in organic synthesis

    Directory of Open Access Journals (Sweden)

    Sambasivarao Kotha

    2015-10-01

    Full Text Available Ring-rearrangement metathesis (RRM involves multiple metathesis processes such as ring-opening metathesis (ROM/ring-closing metathesis (RCM in a one-pot operation to generate complex targets. RRM delivers complex frameworks that are difficult to assemble by conventional methods. The noteworthy point about this type of protocol is multi-bond formation and it is an atom economic process. In this review, we have covered literature that appeared during the last seven years (2008–2014.

  3. Mauve: Multiple Alignment of Conserved Genomic Sequence With Rearrangements

    OpenAIRE

    Darling, Aaron C.E.; Mau, Bob; Blattner, Frederick R.; Perna, Nicole T.

    2004-01-01

    As genomes evolve, they undergo large-scale evolutionary processes that present a challenge to sequence comparison not posed by short sequences. Recombination causes frequent genome rearrangements, horizontal transfer introduces new sequences into bacterial chromosomes, and deletions remove segments of the genome. Consequently, each genome is a mosaic of unique lineage-specific segments, regions shared with a subset of other genomes and segments conserved among all the genomes under considera...

  4. First Claisen Rearrangement Reaction in Ionic Liquids with Microwave Heating

    Institute of Scientific and Technical Information of China (English)

    XU Li-Wen; LI Fu-Wei; XIA Chun-Gu

    2003-01-01

    @@ We have demonstrated the first use of the common ionic liquids, [1] bmimBr, bmimBF4 and bmimPF6 as an environmentally benign solvent for the simple Claisen rearrangement under microwave irradiation. In many cases, the re action was carried out in toxic solvents of high boiling point. [2] Here we reported the first example of Claisen rear rangement reaction in green solvents, ionic liquids, under microwave irradiation.

  5. Fries Rearrangement of Phenyl Acetate over Solid Acid Catalyst

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    A silica-supported zirconium based solid acid (ZS) has been used as catalyst for the Fries rearrangement of phenyl acetate (PA). The catalyst showed a higher PA conversion activity and a much higher selectivity for o-hydroxyacetophenone (o-HAP) than for strongly acidic zeolite catalysts. The supported catalyst was characterized by XRD, IR, XPS, pyridine-TPD and the surface area measurements. The catalytic properties were influenced significantly by pretreatment temperature.

  6. Extended Rearrangement Inequalities and Applications to Some Quantitative Stability Results

    Science.gov (United States)

    Lemou, Mohammed

    2016-09-01

    In this paper, we prove a new functional inequality of Hardy-Littlewood type for generalized rearrangements of functions. We then show how this inequality provides quantitative stability results of steady states to evolution systems that essentially preserve the rearrangements and some suitable energy functional, under minimal regularity assumptions on the perturbations. In particular, this inequality yields a quantitative stability result of a large class of steady state solutions to the Vlasov-Poisson systems, and more precisely we derive a quantitative control of the L 1 norm of the perturbation by the relative Hamiltonian (the energy functional) and rearrangements. A general non linear stability result has been obtained by Lemou et al. (Invent Math 187:145-194, 2012) in the gravitational context, however the proof relied in a crucial way on compactness arguments which by construction provides no quantitative control of the perturbation. Our functional inequality is also applied to the context of 2D-Euler systems and also provides quantitative stability results of a large class of steady-states to this system in a natural energy space.

  7. Three-Color FISH Analysis of TMPRSS2/ERG Fusions in Prostate Cancer Indicates That Genomic Microdeletion of Chromosome 21 Is Associated with Rearrangement

    Directory of Open Access Journals (Sweden)

    Maisa Yoshimoto

    2006-06-01

    Full Text Available The recent description of novel recurrent gene fusions in ~80% of prostate cancer (PCa cases has generated increased interest in the search for new translocations in other epithelial cancers and emphasizes the importance of understanding the origins and biologic implications of these genomic rearrangements. Analysis of 15 PCa cases by reverse transcription-polymerase chain reaction was used to detect six ERG-related gene fusion transcripts with TMPRSS2. No TMPRSS2/ETV1 chimeric fusion was detected in this series. Three-color fluorescence in situ hybridization confirms that TMPRSS2/ERG fusion may be accompanied by a small hemizygous sequence deletion on chromosome 21 between ERG and TMPRSS2 genes. Analysis of genomic architecture in the region of genomic rearrangement suggests that tracts of microhomology could facilitate TMPRSS2/ERG fusion events.

  8. CNOT3 contributes to early B cell development by controlling Igh rearrangement and p53 mRNA stability

    Science.gov (United States)

    Inoue, Takeshi; Morita, Masahiro; Hijikata, Atsushi; Fukuda-Yuzawa, Yoko; Adachi, Shungo; Isono, Kyoichi; Ikawa, Tomokatsu; Kawamoto, Hiroshi; Koseki, Haruhiko; Natsume, Tohru; Fukao, Taro; Ohara, Osamu; Yamamoto, Tadashi

    2015-01-01

    The CCR4–NOT deadenylase complex plays crucial roles in mRNA decay and translational repression induced by poly(A) tail shortening. Although the in vitro activities of each component of this complex have been well characterized, its in vivo role in immune cells remains unclear. Here we show that mice lacking the CNOT3 subunit of this complex, specifically in B cells, have a developmental block at the pro- to pre–B cell transition. CNOT3 regulated generation of germline transcripts in the VH region of the immunoglobulin heavy chain (Igh) locus, compaction of the locus, and subsequent Igh gene rearrangement and destabilized tumor suppressor p53 mRNA. The developmental defect in the absence of CNOT3 could be partially rescued by ablation of p53 or introduction of a pre-rearranged Igh transgene. Thus, our data suggest that the CCR4–NOT complex regulates B cell differentiation by controlling Igh rearrangement and destabilizing p53 mRNA. PMID:26238124

  9. Phylogenetically informative rearrangements in mitochondrial genomes of Coleoptera, and monophyly of aquatic elateriform beetles (Dryopoidea).

    Science.gov (United States)

    Timmermans, Martijn J T N; Vogler, Alfried P

    2012-05-01

    Mitochondrial gene order in Coleoptera has been thought to be conservative but a survey of 60 complete or nearly complete genomes revealed a total of seven different gene rearrangements (deletions, gene order reversals), mainly affecting tRNA genes. All of these were found to be limited to a single taxon or a subclade of Coleoptera. The phylogenetic distribution of a translocation of tRNA(Pro) in three species of elateriform beetles was investigated further by sequencing three nearly complete mitochondrial genomes (Dascillidae, Byrrhidae, Limnichidae) and ten additional individuals for a ∼1370 bp diagnostic fragment spanning the relevant region. Phylogenetic analysis consistently recovered the monophyly of families previously grouped in the contentious superfamily Dryopoidea, a group of approximately 10 beetle families with mainly aquatic lifestyles. The Byrrhidae (moss beetles) were not part of this lineage, although they may be its sister group, to recover the widely accepted Byrrhoidea. The tRNA(Pro) translocation was present in all members of Dryopoidea, but not in any other Elateriformia, providing independent support for this lineage and for a single origin of aquatic habits.

  10. Mitochondrial genome rearrangements in glomus species triggered by homologous recombination between distinct mtDNA haplotypes.

    Science.gov (United States)

    Beaudet, Denis; Terrat, Yves; Halary, Sébastien; de la Providencia, Ivan Enrique; Hijri, Mohamed

    2013-01-01

    Comparative mitochondrial genomics of arbuscular mycorrhizal fungi (AMF) provide new avenues to overcome long-lasting obstacles that have hampered studies aimed at understanding the community structure, diversity, and evolution of these multinucleated and genetically polymorphic organisms.AMF mitochondrial (mt) genomes are homogeneous within isolates, and their intergenic regions harbor numerous mobile elements that have rapidly diverged, including homing endonuclease genes, small inverted repeats, and plasmid-related DNA polymerase genes (dpo), making them suitable targets for the development of reliable strain-specific markers. However, these elements may also lead to genome rearrangements through homologous recombination, although this has never previously been reported in this group of obligate symbiotic fungi. To investigate whether such rearrangements are present and caused by mobile elements in AMF, the mitochondrial genomes from two Glomeraceae members (i.e., Glomus cerebriforme and Glomus sp.) with substantial mtDNA synteny divergence,were sequenced and compared with available glomeromycotan mitochondrial genomes. We used an extensive nucleotide/protein similarity network-based approach to investigated podiversity in AMF as well as in other organisms for which sequences are publicly available. We provide strong evidence of dpo-induced inter-haplotype recombination, leading to a reshuffled mitochondrial genome in Glomus sp. These findings raise questions as to whether AMF single spore cultivations artificially underestimate mtDNA genetic diversity.We assessed potential dpo dispersal mechanisms in AMF and inferred a robust phylogenetic relationship with plant mitochondrial plasmids. Along with other indirect evidence, our analyses indicate that members of the Glomeromycota phylum are potential donors of mitochondrial plasmids to plants.

  11. Gene

    Data.gov (United States)

    U.S. Department of Health & Human Services — Gene integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes,...

  12. Complex rearrangements in patients with duplications of MECP2 can occur by fork stalling and template switching

    Science.gov (United States)

    Carvalho, Claudia M.B.; Zhang, Feng; Liu, Pengfei; Patel, Ankita; Sahoo, Trilochan; Bacino, Carlos A.; Shaw, Chad; Peacock, Sandra; Pursley, Amber; Tavyev, Y. Jane; Ramocki, Melissa B.; Nawara, Magdalena; Obersztyn, Ewa; Vianna-Morgante, Angela M.; Stankiewicz, Pawel; Zoghbi, Huda Y.; Cheung, Sau Wai; Lupski, James R.

    2009-01-01

    Duplication at the Xq28 band including the MECP2 gene is one of the most common genomic rearrangements identified in neurodevelopmentally delayed males. Such duplications are non-recurrent and can be generated by a non-homologous end joining (NHEJ) mechanism. We investigated the potential mechanisms for MECP2 duplication and examined whether genomic architectural features may play a role in their origin using a custom designed 4-Mb tiling-path oligonucleotide array CGH assay. Each of the 30 patients analyzed showed a unique duplication varying in size from ∼250 kb to ∼2.6 Mb. Interestingly, in 77% of these non-recurrent duplications, the distal breakpoints grouped within a 215 kb genomic interval, located 47 kb telomeric to the MECP2 gene. The genomic architecture of this region contains both direct and inverted low-copy repeat (LCR) sequences; this same region undergoes polymorphic structural variation in the general population. Array CGH revealed complex rearrangements in eight patients; in six patients the duplication contained an embedded triplicated segment, and in the other two, stretches of non-duplicated sequences occurred within the duplicated region. Breakpoint junction sequencing was achieved in four duplications and identified an inversion in one patient, demonstrating further complexity. We propose that the presence of LCRs in the vicinity of the MECP2 gene may generate an unstable DNA structure that can induce DNA strand lesions, such as a collapsed fork, and facilitate a Fork Stalling and Template Switching event producing the complex rearrangements involving MECP2. PMID:19324899

  13. The strength of combined cytogenetic and mate-pair sequencing techniques illustrated by a germline chromothripsis rearrangement involving FOXP2

    DEFF Research Database (Denmark)

    Nazaryan, Lusine; Stefanou, Eunice G; Hansen, Claus;

    2014-01-01

    and severe speech disorder. We identified three truncated genes: CDH12, DGKB and FOXP2, confirming the role of FOXP2 in severe speech disorder, and suggestive roles of CDH12 and/or DGKB for the global developmental and psychomotor delay. Our study confirmes the power of MPS for detecting breakpoints...... with many CCRs, none of the reported mate-pair sequenced complex rearrangements have been simultaneously studied with state-of-the art molecular cytogenetic techniques. Here, we studied chromothripsis-associated CCR involving chromosomes 2, 5 and 7, associated with global developmental and psychomotor delay...

  14. Application of the inter-line PCR for the analyse of genomic rearrangements in radiation-transformed mammalian cell lines

    International Nuclear Information System (INIS)

    Repetitive DNA sequences of the LINE-family (long interspersed elements) that are widely distributed among the mammalian genome can be activated or altered by the exposure to ionizing radiation [1]. By the integration at new sites in the genome alterations in the expression of genes that are involved in cell transformation and/or carcinogenesis may occur [2, 3]. A new technique -the inter-LINE PCR - has been developed in order to detect and analyse such genomic rearrangements in radiation-transformed cell lines. From the sites of transformation- or tumour-specific changes in the genome it might be possible to develop new tumour markers for diagnostic purpose. (orig.)

  15. Genome-wide detection of chromosomal rearrangements, indels, and mutations in circular chromosomes by short read sequencing

    DEFF Research Database (Denmark)

    Skovgaard, Ole; Bak, Mads; Løbner-Olesen, Anders;

    2011-01-01

    replication is initiated by assembling two replication complexes at the origin, oriC. These complexes then replicate the chromosome bidirectionally toward the terminus, ter. In a population of growing cells, this results in a copy number gradient, so that origin-proximal sequences are more frequent than...... origin-distal sequences. Major rearrangements in the chromosome are, therefore, readily identified by changes in copy number, i.e., certain sequences become over- or under-represented. Of the eight mutations analyzed in detail here, six were found to affect a single gene only, one was a large chromosomal...

  16. A Role for DNA Polymerase μ in the Emerging DJH Rearrangements of the Postgastrulation Mouse Embryo▿ †

    Science.gov (United States)

    Gozalbo-López, Beatriz; Andrade, Paula; Terrados, Gloria; de Andrés, Belén; Serrano, Natalia; Cortegano, Isabel; Palacios, Beatriz; Bernad, Antonio; Blanco, Luis; Marcos, Miguel A. R.; Gaspar, María Luisa

    2009-01-01

    The molecular complexes involved in the nonhomologous end-joining process that resolves recombination-activating gene (RAG)-induced double-strand breaks and results in V(D)J gene rearrangements vary during mammalian ontogeny. In the mouse, the first immunoglobulin gene rearrangements emerge during midgestation periods, but their repertoires have not been analyzed in detail. We decided to study the postgastrulation DJH joints and compare them with those present in later life. The embryo DJH joints differed from those observed in perinatal life by the presence of short stretches of nontemplated (N) nucleotides. Whereas most adult N nucleotides are introduced by terminal deoxynucleotidyl transferase (TdT), the embryo N nucleotides were due to the activity of the homologous DNA polymerase μ (Polμ), which was widely expressed in the early ontogeny, as shown by analysis of Polμ−/− embryos. Based on its DNA-dependent polymerization ability, which TdT lacks, Polμ also filled in small sequence gaps at the coding ends and contributed to the ligation of highly processed ends, frequently found in the embryo, by pairing to internal microhomology sites. These findings show that Polμ participates in the repair of early-embryo, RAG-induced double-strand breaks and subsequently may contribute to preserve the genomic stability and cellular homeostasis of lymphohematopoietic precursors during development. PMID:19103746

  17. CNV analysis in Tourette syndrome implicates large genomic rearrangements in COL8A1 and NRXN1.

    Science.gov (United States)

    Nag, Abhishek; Bochukova, Elena G; Kremeyer, Barbara; Campbell, Desmond D; Muller, Heike; Valencia-Duarte, Ana V; Cardona, Julio; Rivas, Isabel C; Mesa, Sandra C; Cuartas, Mauricio; Garcia, Jharley; Bedoya, Gabriel; Cornejo, William; Herrera, Luis D; Romero, Roxana; Fournier, Eduardo; Reus, Victor I; Lowe, Thomas L; Farooqi, I Sadaf; Mathews, Carol A; McGrath, Lauren M; Yu, Dongmei; Cook, Ed; Wang, Kai; Scharf, Jeremiah M; Pauls, David L; Freimer, Nelson B; Plagnol, Vincent; Ruiz-Linares, Andrés

    2013-01-01

    Tourette syndrome (TS) is a neuropsychiatric disorder with a strong genetic component. However, the genetic architecture of TS remains uncertain. Copy number variation (CNV) has been shown to contribute to the genetic make-up of several neurodevelopmental conditions, including schizophrenia and autism. Here we describe CNV calls using SNP chip genotype data from an initial sample of 210 TS cases and 285 controls ascertained in two Latin American populations. After extensive quality control, we found that cases (N = 179) have a significant excess (P = 0.006) of large CNV (>500 kb) calls compared to controls (N = 234). Amongst 24 large CNVs seen only in the cases, we observed four duplications of the COL8A1 gene region. We also found two cases with ∼400 kb deletions involving NRXN1, a gene previously implicated in neurodevelopmental disorders, including TS. Follow-up using multiplex ligation-dependent probe amplification (and including 53 more TS cases) validated the CNV calls and identified additional patients with rearrangements in COL8A1 and NRXN1, but none in controls. Examination of available parents indicates that two out of three NRXN1 deletions detected in the TS cases are de-novo mutations. Our results are consistent with the proposal that rare CNVs play a role in TS aetiology and suggest a possible role for rearrangements in the COL8A1 and NRXN1 gene regions.

  18. CNV analysis in Tourette syndrome implicates large genomic rearrangements in COL8A1 and NRXN1.

    Directory of Open Access Journals (Sweden)

    Abhishek Nag

    Full Text Available Tourette syndrome (TS is a neuropsychiatric disorder with a strong genetic component. However, the genetic architecture of TS remains uncertain. Copy number variation (CNV has been shown to contribute to the genetic make-up of several neurodevelopmental conditions, including schizophrenia and autism. Here we describe CNV calls using SNP chip genotype data from an initial sample of 210 TS cases and 285 controls ascertained in two Latin American populations. After extensive quality control, we found that cases (N = 179 have a significant excess (P = 0.006 of large CNV (>500 kb calls compared to controls (N = 234. Amongst 24 large CNVs seen only in the cases, we observed four duplications of the COL8A1 gene region. We also found two cases with ∼400 kb deletions involving NRXN1, a gene previously implicated in neurodevelopmental disorders, including TS. Follow-up using multiplex ligation-dependent probe amplification (and including 53 more TS cases validated the CNV calls and identified additional patients with rearrangements in COL8A1 and NRXN1, but none in controls. Examination of available parents indicates that two out of three NRXN1 deletions detected in the TS cases are de-novo mutations. Our results are consistent with the proposal that rare CNVs play a role in TS aetiology and suggest a possible role for rearrangements in the COL8A1 and NRXN1 gene regions.

  19. A genomewide screen for suppressors of Alu-mediated rearrangements reveals a role for PIF1.

    Directory of Open Access Journals (Sweden)

    Karen M Chisholm

    Full Text Available Alu-mediated rearrangement of tumor suppressor genes occurs frequently during carcinogenesis. In breast cancer, this mechanism contributes to loss of the wild-type BRCA1 allele in inherited disease and to loss of heterozygosity in sporadic cancer. To identify genes required for suppression of Alu-mediated recombination we performed a genomewide screen of a collection of 4672 yeast gene deletion mutants using a direct repeat recombination assay. The primary screen and subsequent analysis identified 12 candidate genes including TSA, ELG1, and RRM3, which are known to play a significant role in maintaining genomic stability. Genetic analysis of the corresponding human homologs was performed in sporadic breast tumors and in inherited BRCA1-associated carcinomas. Sequencing of these genes in high risk breast cancer families revealed a potential role for the helicase PIF1 in cancer predisposition. PIF1 variant L319P was identified in three breast cancer families; importantly, this variant, which is predicted to be functionally damaging, was not identified in a large series of controls nor has it been reported in either dbSNP or the 1000 Genomes Project. In Schizosaccharomyces pombe, Pfh1 is required to maintain both mitochondrial and nuclear genomic integrity. Functional studies in yeast of human PIF1 L319P revealed that this variant cannot complement the essential functions of Pfh1 in either the nucleus or mitochondria. Our results provide a global view of nonessential genes involved in suppressing Alu-mediated recombination and implicate variation in PIF1 in breast cancer predisposition.

  20. Precise detection of rearrangement breakpoints in mammalian chromosomes

    Directory of Open Access Journals (Sweden)

    Gautier Christian

    2008-06-01

    Full Text Available Abstract Background Genomes undergo large structural changes that alter their organisation. The chromosomal regions affected by these rearrangements are called breakpoints, while those which have not been rearranged are called synteny blocks. We developed a method to precisely delimit rearrangement breakpoints on a genome by comparison with the genome of a related species. Contrary to current methods which search for synteny blocks and simply return what remains in the genome as breakpoints, we propose to go further and to investigate the breakpoints themselves in order to refine them. Results Given some reliable and non overlapping synteny blocks, the core of the method consists in refining the regions that are not contained in them. By aligning each breakpoint sequence against its specific orthologous sequences in the other species, we can look for weak similarities inside the breakpoint, thus extending the synteny blocks and narrowing the breakpoints. The identification of the narrowed breakpoints relies on a segmentation algorithm and is statistically assessed. Since this method requires as input synteny blocks with some properties which, though they appear natural, are not verified by current methods for detecting such blocks, we further give a formal definition and provide an algorithm to compute them. The whole method is applied to delimit breakpoints on the human genome when compared to the mouse and dog genomes. Among the 355 human-mouse and 240 human-dog breakpoints, 168 and 146 respectively span less than 50 Kb. We compared the resulting breakpoints with some publicly available ones and show that we achieve a better resolution. Furthermore, we suggest that breakpoints are rarely reduced to a point, and instead consist in often large regions that can be distinguished from the sequences around in terms of segmental duplications, similarity with related species, and transposable elements. Conclusion Our method leads to smaller

  1. Autosomal rearrangement in Gryllus assimilis Fabricius, 1775 (Orthoptera, Gryllidae)

    OpenAIRE

    Edison Zefa

    1999-01-01

    Gryllus assimilis L. has a karyotype of 2n = 29 (X0, male) and 30 (XX, female). The above karyotype was encountered along with another in which 2n = 28 (X0, male) and 2n = 29 (XX, female) in a population from the outskirts of Rio Claro city (São Paulo State, Brazil). Of eight specimens studied, five had the heterozygous karyotype involving a translocation and three had the basic karyotype. There were no individuals homozygous for the rearrangement. The heterozygous karyotype was the result of...

  2. Confining Bond Rearrangement in the Random Center Vortex Model

    CERN Document Server

    Altarawneh, Derar; Engelhardt, Michael

    2015-01-01

    We present static meson-meson and baryon--anti-baryon potentials in Z(2) and Z(3) random center vortex models for the infrared sector of Yang-Mills theory, i.e., hypercubic lattice models of random vortex world-surfaces. In particular, we calculate Polyakov loop correlators of two static mesons resp. (anti-)baryons in a center vortex background and observe that their expectation values follow the minimal area law and show bond rearrangement behavior. The static meson-meson and baryon--anti-baryon potentials are compared with theoretical predictions and lattice QCD simulations.

  3. Confining bond rearrangement in the random center vortex model

    Science.gov (United States)

    Altarawneh, Derar; Höllwieser, Roman; Engelhardt, Michael

    2016-03-01

    We present static meson-meson and baryon-antibaryon potentials in Z (2 ) and Z (3 ) random center vortex models for the infrared sector of Yang-Mills theory, i.e., hypercubic lattice models of random vortex world surfaces. In particular, we calculate multiple Polyakov loop correlators corresponding to static meson-meson or baryon-antibaryon configurations in a center vortex background and observe that their expectation values follow the minimal area law, displaying bond rearrangement behavior, a characteristic expected for the confining dynamics of the strong interaction. The static meson-meson and baryon-antibaryon potentials are compared with theoretical predictions and lattice QCD simulations.

  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.

    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.

  6. 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)

  7. Constitutional Chromothripsis Rearrangements Involve Clustered Double-Stranded DNA Breaks and Nonhomologous Repair Mechanisms

    Directory of Open Access Journals (Sweden)

    Wigard P. Kloosterman

    2012-06-01

    Full Text Available Chromothripsis represents a novel phenomenon in the structural variation landscape of cancer genomes. Here, we analyze the genomes of ten patients with congenital disease who were preselected to carry complex chromosomal rearrangements with more than two breakpoints. The rearrangements displayed unanticipated complexity resembling chromothripsis. We find that eight of them contain hallmarks of multiple clustered double-stranded DNA breaks (DSBs on one or more chromosomes. In addition, nucleotide resolution analysis of 98 breakpoint junctions indicates that break repair involves nonhomologous or microhomology-mediated end joining. We observed that these eight rearrangements are balanced or contain sporadic deletions ranging in size between a few hundred base pairs and several megabases. The two remaining complex rearrangements did not display signs of DSBs and contain duplications, indicative of rearrangement processes involving template switching. Our work provides detailed insight into the characteristics of chromothripsis and supports a role for clustered DSBs driving some constitutional chromothripsis rearrangements.

  8. Most ultraviolet irradiation induced mutations in the nematode Caenorhabditis elegans are chromosomal rearrangements

    Energy Technology Data Exchange (ETDEWEB)

    Stewart, H.I.; Rosenbluth, R.E.; Baillie, D.L. (Simon Fraser University, Burnaby, BC (Canada). Department of Biological Sciences, Institute of Molecular Biology)

    1991-07-01

    In this study the utility of 254-nm ultraviolet light (UV) as a magnetic tool in C.elegans is determined. It is demonstrated that irradiation of adult hermaphrodites provides a simple method for the induction of heritable chromosomal rearrangements. A screening protocol was employed that identifies either recessive lethal mutations in the 40 map unit region balanced by the translocation eT1(III;V), or unc-36(III) duplications. Mutations were recovered in 3% of the chromosomes screened after a dose of 120 J/m{sup 2}. This rate resembles that for 1500 R {gamma}-ray-induced mutations selected in a similar manner. The mutations were classified either as lethals (mapping to Linkage Group (LG)III or LGV) or as putative unc-36 duplications. In contrast to the majority of UV-induced mutations analysed in micro-organisms, a large fraction of the C.elegans UV-induced mutations were found to be not simple intragenic lesions, but deficiencies for more than one adjacent gene or more complex events. Preliminary evidence for this conclusion came from the high frequency of mutations that had a dominant effect causing reduced numbers of adult progeny. Subsequently 6 out of 9 analysed LGV mutations were found to be deficiencies. Other specific rearrangements also identified were: one translocation, sT5(II;III), and two unc-36 duplications, sDp8 and sDp9. It was concluded that UV irradiation can easily be used as an additional tool for the analysis of C.elegans chromosomes, and that C.elegans should prove to be a useful organism in which to study the mechanisms whereby UV acts as a mutagen in cells of complex eukaryotes. (author). 46 refs.; 5 figs.; 4 tabs.

  9. Copy-number gains of HUWE1 due to replication- and recombination-based rearrangements.

    Science.gov (United States)

    Froyen, Guy; Belet, Stefanie; Martinez, Francisco; Santos-Rebouças, Cíntia Barros; Declercq, Matthias; Verbeeck, Jelle; Donckers, Lene; Berland, Siren; Mayo, Sonia; Rosello, Monica; Pimentel, Márcia Mattos Gonçalves; Fintelman-Rodrigues, Natalia; Hovland, Randi; Rodrigues dos Santos, Suely; Raymond, F Lucy; Bose, Tulika; Corbett, Mark A; Sheffield, Leslie; van Ravenswaaij-Arts, Conny M A; Dijkhuizen, Trijnie; Coutton, Charles; Satre, Veronique; Siu, Victoria; Marynen, Peter

    2012-08-10

    We previously reported on nonrecurrent overlapping duplications at Xp11.22 in individuals with nonsyndromic intellectual disability (ID) harboring HSD17B10, HUWE1, and the microRNAs miR-98 and let-7f-2 in the smallest region of overlap. Here, we describe six additional individuals with nonsyndromic ID and overlapping microduplications that segregate in the families. High-resolution mapping of the 12 copy-number gains reduced the minimal duplicated region to the HUWE1 locus only. Consequently, increased mRNA levels were detected for HUWE1, but not HSD17B10. Marker and SNP analysis, together with identification of two de novo events, suggested a paternally derived intrachromosomal duplication event. In four independent families, we report on a polymorphic 70 kb recurrent copy-number gain, which harbors part of HUWE1 (exon 28 to 3' untranslated region), including miR-98 and let-7f-2. Our findings thus demonstrate that HUWE1 is the only remaining dosage-sensitive gene associated with the ID phenotype. Junction and in silico analysis of breakpoint regions demonstrated simple microhomology-mediated rearrangements suggestive of replication-based duplication events. Intriguingly, in a single family, the duplication was generated through nonallelic homologous recombination (NAHR) with the use of HUWE1-flanking imperfect low-copy repeats, which drive this infrequent NAHR event. The recurrent partial HUWE1 copy-number gain was also generated through NAHR, but here, the homologous sequences used were identified as TcMAR-Tigger DNA elements, a template that has not yet been reported for NAHR. In summary, we showed that an increased dosage of HUWE1 causes nonsyndromic ID and demonstrated that the Xp11.22 region is prone to recombination- and replication-based rearrangements.

  10. Rearrangement mechanism of the sodium adducts of Fmoc protected amino acids

    Institute of Scientific and Technical Information of China (English)

    DU Jintang; LI Yanmei; ZHU Zhentai; CHEN Yi; ZHAO Yufen

    2003-01-01

    The cationized 9-fluorenylmethoxycarbonyl (Fmoc) protected amino acidswere analyzed by the electrospray ionization tandem mass spectrometry (ESI-MS/MS). A rearrangement reaction leading to the C-terminal hydroxyl group transfer was observed. The sodium adducts of Fmoc-OH was formed. A possible rearrangement mechanism was proposed. The rearrangement reaction depended on the Fmoc group, metal ions and metal ion radius. It was shown that the Fmoc group has a strong affinity to the hydroxyl group in the gas phase.

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

    Directory of Open Access Journals (Sweden)

    Rongen Michel A

    2009-07-01

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

  12. Dose dependent rearrangement of cellular membranes induced by ionizing radiation

    International Nuclear Information System (INIS)

    The radiation-induced effects at dose rate of 0.35 Gy/min (in vivo) and of ultra-low doses (in vitro) on the cell membranes structural state were shown. The modifications of the membrane protein and lipid components and their dynamic state were revealed at experimental irradiation conditions by fluorescent probe analysis. The principal component analysis of the research data indicates the dose-dependent decrease of plasma membrane structural orderliness of the small intestine enterocytes with the increase of the ionizing irradiation acute dose of 0.5, 1.0, 2.0, 3.0 Gy at dose rate of 0.35 Gy/min. The complex response of the biological structure - the erythrocytes plasma membrane, on the ionizing radiation action at ultra-low doses that occurred through macromolecular structural rearrangements was also demonstrated. The features of the structural rearrangement of the cellular membranes depending on the ionizing radiation dose (dose rate) are found out

  13. FASEB Summer Research Conference. Genetic Recombination and Chromosome Rearrangements

    Energy Technology Data Exchange (ETDEWEB)

    Jinks-Robertson, Sue

    2002-02-01

    The 2001 meeting entitled ''Genetic Recombination and Genome Rearrangements'' was held July 21-26 in Snowmass, Colorado. The goal of the meeting was to bring together scientists using diverse approaches to study all aspects of genetic recombination. This goal was achieved by integrating talks covering the genetics, biochemistry and structural biology of homologous recombination, site-specific recombination, and nonhomologous recombination. The format of the meeting consisted of a keynote address on the opening evening, two formal plenary sessions on each of the four full meeting days, a single afternoon workshop consisting of short talks chosen from among submitted abstracts, and afternoon poster sessions on each of the four full meeting days. The eight plenary session were entitled: (1) Recombination Mechanisms, (2) Prokaryotic Recombination, (3) Repair and Recombination, (4) Site-specific Recombination and Transposition, (5) Eukaryotic Recombination I, (6) Genome Rearrangements, (7) Meiosis, and (8) Eukaryotic Recombination II. Each session included a mix of genetic, biochemical and structural talks; talks were limited to 20 minutes, followed by 10 minutes of very lively, general discussion. Much of the data presented in the plenary sessions was unpublished, thus providing attendees with the most up-to-date knowledge of this rapidly-moving field.

  14. Chromosomal rearrangements and the pathogenesis of differentiated thyroid cancer

    Directory of Open Access Journals (Sweden)

    Stefan K.G. Grebe

    2011-12-01

    Full Text Available The majority of thyroid cancers arise from the follicular cells of the thyroid gland, which yield a wide variety of distinct morphotypes, ranging from relatively indolent lesions to the most malignant forms of cancer known. The remaining primary thyroid cancers arise from C cells within the gland and result primarily from mutations of the RET protooncogene, germ line mutations of which give rise to the various forms of multiple endocrine neoplasia. The most common of the follicular cell-derived cancers are papillary carcinomas, (PTC, followed by follicular carcinomas (FTC and its Hurthle cell variant (HCC and finally anaplastic carcinomas (ATC. The pathogenesis of many thyroid cancers, of both PTC and FTC morphotype, involves chromosomal translocations. Rearrangements of the RET protoconcogene are known to be involved in the pathogenesis of ca. 50% of PTC. A similar proportion of FTC have been associated with a t(2;3(q13;p25 translocation, fusing the thyroid-specific transcription factor PAX8 with the peroxisome proliferator-activated receptor gamma (PPARγ nuclear receptor, a ubiquitously expressed transcription factor. These rearrangements have analogy with translocations in erythropoetic cells, which form the only other known group of human malignancies that are largely the result of chromosomal translocation events. In this review we compare and contrast the oncogenic properties of thyroid and erythroid chromosomal transformations and speculate on mechanisms leading to their formation.

  15. Diffusing Diffusivity: Survival in a Crowded Rearranging and Bounded Domain.

    Science.gov (United States)

    Jain, Rohit; Sebastian, Kizhakeyil L

    2016-09-01

    We consider a particle diffusing in a bounded, crowded, rearranging medium. The rearrangement happens on a time scale longer than the typical time scale of diffusion of the particle; as a result, effectively, the diffusion coefficient of the particle varies as a stochastic function of time. What is the probability that the particle will survive within the bounded region, given that it is absorbed the first time it hits the boundary of the region in which it diffuses? This question is of great interest in a variety of chemical and biological problems. If the diffusion coefficient is a constant, then analytical solutions for a variety of cases are available in the literature. However, there is no solution available for the case in which the diffusion coefficient is a random function of time. We discuss a class of models for which it is possible to find analytical solutions to the problem. We illustrate the method for a circular, two-dimensional region, but our methods are easy to apply to diffusion in arbitrary dimensions and spherical/rectangular regions. Our solution shows that if the dimension of the region is large, then only the average value of the diffusion coefficient determines the survival probability. However, for smaller-sized regions, one would be able to see the effects of the stochasticity of the diffusion coefficient. We also give generalizations of the results to N dimensions. PMID:27478982

  16. Quantifying stretching and rearrangement in epithelial sheet migration

    CERN Document Server

    Lee, Rachel M; Nordstrom, Kerstin N; Ouellette, Nicholas T; Losert, Wolfgang; 10.1088/1367-2630/15/2/025036

    2013-01-01

    Although understanding the collective migration of cells, such as that seen in epithelial sheets, is essential for understanding diseases such as metastatic cancer, this motion is not yet as well characterized as individual cell migration. Here we adapt quantitative metrics used to characterize the flow and deformation of soft matter to contrast different types of motion within a migrating sheet of cells. Using a Finite-Time Lyapunov Exponent (FTLE) analysis, we find that - in spite of large fluctuations - the flow field of an epithelial cell sheet is not chaotic. Stretching of a sheet of cells (i.e., positive FTLE) is localized at the leading edge of migration. By decomposing the motion of the cells into affine and non-affine components using the metric D$^{2}_{min}$, we quantify local plastic rearrangements and describe the motion of a group of cells in a novel way. We find an increase in plastic rearrangements with increasing cell densities, whereas inanimate systems tend to exhibit less non-affine rearran...

  17. Micro-cost Analysis of ALK Rearrangement Testing by FISH to Determine Eligibility for Crizotinib Therapy in NSCLC: Implications for Cost Effectiveness of Testing and Treatment

    OpenAIRE

    David Parker; Marc-Antoine Belaud-Rotureau

    2014-01-01

    Break-apart fluorescence in situ hybridization (FISH) is the gold standard test for anaplastic lymphoma kinase (ALK) gene rearrangement. However, this methodology often is assumed to be expensive and potentially cost-prohibitive given the low prevalence of ALK-positive non-small cell lung cancer (NSCLC) cases. To more accurately estimate the cost of ALK testing by FISH, we developed a micro-cost model that accounts for all cost elements of the assay, including laboratory reagents, supplies, c...

  18. Genetic rearrangements of six wheat-agropyron cristatum 6P addition lines revealed by molecular markers.

    Directory of Open Access Journals (Sweden)

    Haiming Han

    Full Text Available Agropyron cristatum (L. Gaertn. (2n = 4x = 28, PPPP not only is cultivated as pasture fodder but also could provide many desirable genes for wheat improvement. It is critical to obtain common wheat-A. cristatum alien disomic addition lines to locate the desired genes on the P genome chromosomes. Comparative analysis of the homoeologous relationships between the P genome chromosome and wheat genome chromosomes is a key step in transferring different desirable genes into common wheat and producing the desired alien translocation line while compensating for the loss of wheat chromatin. In this study, six common wheat-A. cristatum disomic addition lines were produced and analyzed by phenotypic examination, genomic in situ hybridization (GISH, SSR markers from the ABD genomes and STS markers from the P genome. Comparative maps, six in total, were generated and demonstrated that all six addition lines belonged to homoeologous group 6. However, chromosome 6P had undergone obvious rearrangements in different addition lines compared with the wheat chromosome, indicating that to obtain a genetic compensating alien translocation line, one should recombine alien chromosomal regions with homoeologous wheat chromosomes. Indeed, these addition lines were classified into four types based on the comparative mapping: 6PI, 6PII, 6PIII, and 6PIV. The different types of chromosome 6P possessed different desirable genes. For example, the 6PI type, containing three addition lines, carried genes conferring high numbers of kernels per spike and resistance to powdery mildew, important traits for wheat improvement. These results may prove valuable for promoting the development of conventional chromosome engineering techniques toward molecular chromosome engineering.

  19. [1,2]-Wittig Rearrangement of THP Acetal Compounds: Facile Synthesis of Aromatic Tertiary Alcohols

    Directory of Open Access Journals (Sweden)

    Feng-Lei Gu

    2011-01-01

    Full Text Available Several sec-aromatic THP acetal compounds have been found to be suitable substrates for the [1,2]-Wittig rearrangement in the absence of an external electrophile, which resulted in the generation of new carbon-carbon bond and the facile synthesis of aromatic tertiary alcohols. More interestingly, an unexpected effect of chlorotrimethylsilane on this [1,2]-Wittig rearrangement of sec-aromatic THP acetal compounds was found, in which two different products involving oxidative procedure were obtained due to the competitive [1,4]-Sigmatropic rearrangement versus [1,2]-Wittig rearrangement

  20. Nuclear positioning, higher-order folding, and gene expression of Mmu15 sequences are refractory to chromosomal translocation

    OpenAIRE

    Snow, Kathy J.; Wright, Sarah M.; Woo, Yong; Titus, Laura C.; Mills, Kevin D.; Shopland, Lindsay S.

    2010-01-01

    Nuclear localization influences the expression of certain genes. Chromosomal rearrangements can reposition genes in the nucleus and thus could impact the expression of genes far from chromosomal breakpoints. However, the extent to which chromosomal rearrangements influence nuclear organization and gene expression is poorly understood. We examined mouse progenitor B cell lymphomas with a common translocation, der(12)t(12;15), which fuses a gene-rich region of mouse chromosome12 (Mmu12) with a ...

  1. ATR-16 due to a de novo complex rearrangement of chromosome 16.

    Science.gov (United States)

    Gallego, Marta S; Zelaya, Gabriela; Feliu, Aurora S; Rossetti, Liliana; Shaffer, Lisa G; Bailey, Kristen A; Bacino, Carlos A; Barreiro, Cristina Z

    2005-01-01

    We describe a child with ATR-16 [alpha-thalassemia (thal)/mental retardation], who was referred for genetic evaluation because of minor anomalies and developmental delay. Cytogenetic analysis demonstrated a de novo complex rearrangement of chromosome 16. Fluorescence in situ hybridization (FISH) analysis, using chromosome 16 subtelomeric probes, showed that this patient had a deletion of the distal short arm of chromosome 16 that contains the alpha-globin genes and a duplication of 16q. Analysis of the alpha-globin locus by Southern blot showed a half normal dose of the alpha-globin gene. Microsatellite marker studies revealed that the duplicated 16q region was maternal in origin. Hematological studies revealed anemia, hypochromia and occasional cells with Hb H inclusion bodies. A hematological screening for alpha-thal should be considered in patients with mild developmental delay and a suggestive phenotype of ATR-16 with microcytic hypochromic anemia and normal iron status. The stellate pattern of the iris, a new finding in our patient, may contribute to a better clinical delineation of both syndromes, ATR-16 and/or duplication of 16qter.

  2. Rearrangement of actin cytoskeleton mediates invasion of Lotus japonicus roots by Mesorhizobium loti.

    Science.gov (United States)

    Yokota, Keisuke; Fukai, Eigo; Madsen, Lene H; Jurkiewicz, Anna; Rueda, Paloma; Radutoiu, Simona; Held, Mark; Hossain, Md Shakhawat; Szczyglowski, Krzysztof; Morieri, Giulia; Oldroyd, Giles E D; Downie, J Allan; Nielsen, Mette W; Rusek, Anna Maria; Sato, Shusei; Tabata, Satoshi; James, Euan K; Oyaizu, Hiroshi; Sandal, Niels; Stougaard, Jens

    2009-01-01

    Infection thread-dependent invasion of legume roots by rhizobia leads to internalization of bacteria into the plant cells, which is one of the salient features of root nodule symbiosis. We found that two genes, Nap1 (for Nck-associated protein 1) and Pir1 (for 121F-specific p53 inducible RNA), involved in actin rearrangements were essential for infection thread formation and colonization of Lotus japonicus roots by its natural microsymbiont, Mesorhizobium loti. nap1 and pir1 mutants developed an excess of uncolonized nodule primordia, indicating that these two genes were not essential for the initiation of nodule organogenesis per se. However, both the formation and subsequent progression of infection threads into the root cortex were significantly impaired in these mutants. We demonstrate that these infection defects were due to disturbed actin cytoskeleton organization. Short root hairs of the mutants had mostly transverse or web-like actin filaments, while bundles of actin filaments in wild-type root hairs were predominantly longitudinal. Corroborating these observations, temporal and spatial differences in actin filament organization between wild-type and mutant root hairs were also observed after Nod factor treatment, while calcium influx and spiking appeared unperturbed. Together with various effects on plant growth and seed formation, the nap1 and pir1 alleles also conferred a characteristic distorted trichome phenotype, suggesting a more general role for Nap1 and Pir1 in processes establishing cell polarity or polar growth in L. japonicus.

  3. Ploidy influences cellular responses to gross chromosomal rearrangements in saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    Lemoine Sophie

    2011-06-01

    Full Text Available Abstract Background Gross chromosomal rearrangements (GCRs such as aneuploidy are key factors in genome evolution as well as being common features of human cancer. Their role in tumour initiation and progression has not yet been completely elucidated and the effects of additional chromosomes in cancer cells are still unknown. Most previous studies in which Saccharomyces cerevisiae has been used as a model for cancer cells have been carried out in the haploid context. To obtain new insights on the role of ploidy, the cellular effects of GCRs were compared between the haploid and diploid contexts. Results A total number of 21 haploid and diploid S. cerevisiae strains carrying various types of GCRs (aneuploidies, nonreciprocal translocations, segmental duplications and deletions were studied with a view to determining the effects of ploidy on the cellular responses. Differences in colony and cell morphology as well as in the growth rates were observed between mutant and parental strains. These results suggest that cells are impaired physiologically in both contexts. We also investigated the variation in genomic expression in all the mutants. We observed that gene expression was significantly altered. The data obtained here clearly show that genes involved in energy metabolism, especially in the tricarboxylic acid cycle, are up-regulated in all these mutants. However, the genes involved in the composition of the ribosome or in RNA processing are down-regulated in diploids but up-regulated in haploids. Over-expression of genes involved in the regulation of the proteasome was found to occur only in haploid mutants. Conclusion The present comparisons between the cellular responses of strains carrying GCRs in different ploidy contexts bring to light two main findings. First, GCRs induce a general stress response in all studied mutants, regardless of their ploidy. Secondly, the ploidy context plays a crucial role in maintaining the stoichiometric balance

  4. Rearrangement procedures in regenerative multibeammobile communications satellites with frequency reuse

    Science.gov (United States)

    Colombo, Gianni; Settimo, Franco; Vernucci, Antonio

    1988-01-01

    After a short overview on the European tendencies about a Land Mobile Satellite Service, this paper describes an advanced system architecture, based on multiple spot-beams and on-board processing, capable of providing message and voice services over a wide European coverage, including some North-Africa and Middle-East countries. A remarkable problem associated with spot-beam configurations is the requirement for flexibility in the capacity offer to the various coverage areas. This means incorporating procedures for changing the on-board modulator-to-spot associations, respecting the constraints imposed by frequency reuse. After discussing the requirements of the rearrangement procedure, an on-purpose algorithm is presented. This paper is derived from work performed on contract to the European Space Agency (ESA).

  5. Charge carrier rearrangement in spinel crystals irradiated at low temperatures

    International Nuclear Information System (INIS)

    The results of an investigation of thermoluminescence (TL) in nominally pure MgAl2O4 spinel single crystals in the temperature range between 80-670 K are presented. For a heating rate of 0.21 K/s, TL spectra exhibit glow peaks in three distinct temperature ranges: 100-160, 270-370 and 470-670 K. The most prominent peaks are at 115, 140, 305, 335, 525, 570 and 605 K. The locations of the temperature maxima, as well as the intensity of the peaks, vary depending on the treatment of the crystals, the type of irradiation and the temperature of irradiation. Measurements of the glow peaks at different emission wavelengths and the use of partial bleaching and isothermal decay techniques for TL, allowed us to propose mechanisms for charge carrier rearrangement at lattice defects and impurity ions, during irradiation and subsequent heating

  6. SYNTHESIS OF ALLYL PHENYL ETHER AND CLAISEN REARRANGEMENT

    Directory of Open Access Journals (Sweden)

    Gagik Torosyan

    2011-12-01

    Full Text Available It has been established the possibility for phenol allylation on natural zeolites and them analogs. Here is demonstrated the synthesis of allyl phenol, which has wide industrial applications. The offered method in comparison with the traditional methods has more advantages – higher selectivity, smaller material and power resources consumption. It has been obtained the mixture of allylating phenols (30% in general with allyl phenyl ether (1 with 80% yields. At 600 K is obtained allylphenyl ether, at 700 K beginning the formation of allyl phenols, which is the result of direct C-allylation of the aromatic ring. It has been investigated the possibility of Claisen rearrangement in the same conditions. All of that are established by gas-liquid chromatography and liquid chromatography data.

  7. Improved outcome with hematopoietic stem cell transplantation in a poor prognostic subgroup of infants with mixed-lineage-leukemia (MLL)-rearranged acute lymphoblastic leukemia: results from the Interfant-99 Study

    DEFF Research Database (Denmark)

    Mann, Georg; Attarbaschi, Andishe; Schrappe, Martin;

    2010-01-01

    To define a role for hematopoietic stem cell transplantation (HSCT) in infants with acute lymphoblastic leukemia and rearrangements of the mixed-lineage-leukemia gene (MLL(+)), we compared the outcome of MLL(+) patients from trial Interfant-99 who either received chemotherapy only or HSCT. Of 376...

  8. Recent applications of the divinylcyclopropane–cycloheptadiene rearrangement in organic synthesis

    Directory of Open Access Journals (Sweden)

    Sebastian Krüger

    2014-01-01

    Full Text Available This review summarizes the application of the divinylcyclopropane–cycloheptadiene rearrangement in synthetic organic chemistry. A brief overview of the new mechanistic insights concerning the title reaction is provided as well as a condensed account on the biological relevance of the topic. Heteroatom variants of this rearrangement are covered briefly.

  9. Recent applications of the divinylcyclopropane–cycloheptadiene rearrangement in organic synthesis

    Science.gov (United States)

    Krüger, Sebastian

    2014-01-01

    Summary This review summarizes the application of the divinylcyclopropane–cycloheptadiene rearrangement in synthetic organic chemistry. A brief overview of the new mechanistic insights concerning the title reaction is provided as well as a condensed account on the biological relevance of the topic. Heteroatom variants of this rearrangement are covered briefly. PMID:24605138

  10. Lecture Capture with Real-Time Rearrangement of Visual Elements: Impact on Student Performance

    Science.gov (United States)

    Yu, P.-T.; Wang, B.-Y.; Su, M.-H.

    2015-01-01

    The primary goal of this study is to create and test a lecture-capture system that can rearrange visual elements while recording is still taking place, in such a way that student performance can be positively influenced. The system we have devised is capable of integrating and rearranging multimedia sources, including learning content, the…

  11. Chromosome 6p rearrangements appear to be secondary changes in various haematological malignancies.

    Science.gov (United States)

    Huret, J L; Schoenwald, M; Brizard, A; Guilhot, F; Vilmer, E; Tanzer, J

    1989-01-01

    We report on six cases of 6p rearrangement in various haematological malignancies. On reviewing the literature, we assume 6p rearrangements to be secondary anomalies in both myeloid and lymphoid malignancies, and confirm it to be strongly associated with -5/del (5q) in myelodysplastic syndromes.

  12. A Novel Method for Beckmann Rearrangement of Oximes with Silica Sulfuric Acid under Mild Condition

    Institute of Scientific and Technical Information of China (English)

    Lin Fei XIAO; Jia Jian PENG; Chun Gu XIA

    2006-01-01

    Silica sulfuric acid in which sulfuric acid is immobilized on the surface of silica gel via covalent bond has been proved to be green catalyst for liquid-phase Beckmann rearrangement of oximes in dried dioxane at room temperature. Excellent conversion and selectivity were acquired in the Beckmann rearrangement of cyclohexanone oxime. The catalyst system was recycled and reused.

  13. Regioselective synthesis of heteroaryl triflones by LDA (lithium diisopropylamide)-mediated anionic thia-Fries rearrangement.

    Science.gov (United States)

    Xu, Xiu-Hua; Wang, Xin; Liu, Guo-kai; Tokunaga, Etsuko; Shibata, Norio

    2012-05-18

    Novel heteroaryl triflones including oxindole, pyrazolone, pyridine, and quinoline derivatives have been regioselectively synthesized by LDA-mediated thia-Fries rearrangement for the first time. These reactions are also the first examples of the application of anionic thia-Fries rearrangement in heteroaromatic compounds.

  14. Germline rearrangements in families with strong family history of glioma and malignant melanoma, colon, and breast cancer

    DEFF Research Database (Denmark)

    Andersson, Ulrika; Wibom, Carl; Cederquist, Kristina;

    2014-01-01

    BACKGROUND: Although familial susceptibility to glioma is known, the genetic basis for this susceptibility remains unidentified in the majority of glioma-specific families. An alternative approach to identifying such genes is to examine cancer pedigrees, which include glioma as one of several can...... colon cancer. CONCLUSIONS: Large deletions and duplications are rare events in familial glioma cases, even in families with a strong family history of cancers that may be involved in known cancer syndromes.......BACKGROUND: Although familial susceptibility to glioma is known, the genetic basis for this susceptibility remains unidentified in the majority of glioma-specific families. An alternative approach to identifying such genes is to examine cancer pedigrees, which include glioma as one of several...... cancer phenotypes, to determine whether common chromosomal modifications might account for the familial aggregation of glioma and other cancers. METHODS: Germline rearrangements in 146 glioma families (from the Gliogene Consortium; http://www.gliogene.org/) were examined using multiplex ligation...

  15. MSOAR 2.0: Incorporating tandem duplications into ortholog assignment based on genome rearrangement

    Directory of Open Access Journals (Sweden)

    Zhang Liqing

    2010-01-01

    Full Text Available Abstract Background Ortholog assignment is a critical and fundamental problem in comparative genomics, since orthologs are considered to be functional counterparts in different species and can be used to infer molecular functions of one species from those of other species. MSOAR is a recently developed high-throughput system for assigning one-to-one orthologs between closely related species on a genome scale. It attempts to reconstruct the evolutionary history of input genomes in terms of genome rearrangement and gene duplication events. It assumes that a gene duplication event inserts a duplicated gene into the genome of interest at a random location (i.e., the random duplication model. However, in practice, biologists believe that genes are often duplicated by tandem duplications, where a duplicated gene is located next to the original copy (i.e., the tandem duplication model. Results In this paper, we develop MSOAR 2.0, an improved system for one-to-one ortholog assignment. For a pair of input genomes, the system first focuses on the tandemly duplicated genes of each genome and tries to identify among them those that were duplicated after the speciation (i.e., the so-called inparalogs, using a simple phylogenetic tree reconciliation method. For each such set of tandemly duplicated inparalogs, all but one gene will be deleted from the concerned genome (because they cannot possibly appear in any one-to-one ortholog pairs, and MSOAR is invoked. Using both simulated and real data experiments, we show that MSOAR 2.0 is able to achieve a better sensitivity and specificity than MSOAR. In comparison with the well-known genome-scale ortholog assignment tool InParanoid, Ensembl ortholog database, and the orthology information extracted from the well-known whole-genome multiple alignment program MultiZ, MSOAR 2.0 shows the highest sensitivity. Although the specificity of MSOAR 2.0 is slightly worse than that of InParanoid in the real data experiments

  16. Promoter methylation and large intragenic rearrangements of DPYD are not implicated in severe toxicity to 5-fluorouracil-based chemotherapy in gastrointestinal cancer patients

    International Nuclear Information System (INIS)

    Severe toxicity to 5-fluorouracil (5-FU) based chemotherapy in gastrointestinal cancer has been associated with constitutional genetic alterations of the dihydropyrimidine dehydrogenase gene (DPYD). In this study, we evaluated DPYD promoter methylation through quantitative methylation-specific PCR and screened DPYD for large intragenic rearrangements in peripheral blood from 45 patients with gastrointestinal cancers who developed severe 5-FU toxicity. DPYD promoter methylation was also assessed in tumor tissue from 29 patients Two cases with the IVS14+1G > A exon 14 skipping mutation (c.1905+1G > A), and one case carrying the 1845 G > T missense mutation (c.1845G > T) in the DPYD gene were identified. However, DPYD promoter methylation and large DPYD intragenic rearrangements were absent in all cases analyzed. Our results indicate that DPYD promoter methylation and large intragenic rearrangements do not contribute significantly to the development of 5-FU severe toxicity in gastrointestinal cancer patients, supporting the need for additional studies on the mechanisms underlying genetic susceptibility to severe 5-FU toxicity

  17. Dienone-phenol Rearrangement of C-9 Oxygenated Decalinic Dienone and Analogs through B-Ring Cleavage

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Dehydrogenation of 9-hydroxy decalinic enones and analogs with DDQ resulted in a formal dienone-phenol type rearrangement via B-ring cleavage, while the corresponding dienone acetates underwent base-catalyzed formal dienone-phenol type rearrangement analogously.

  18. Frequency and variability of genomic rearrangements on MSH2 in Spanish Lynch Syndrome families.

    Directory of Open Access Journals (Sweden)

    Atocha Romero

    Full Text Available Large genomic rearrangements (LGRs in DNA-mismatch-repair (MMR genes, particularly among MSH2 gene, are frequently involved in the etiology of Lynch syndrome (LS. The Multiplex Ligation and Probe Amplification assay (MLPA is commonly used to identify such alterations. However, in most cases, the MLPA-identified alteration is not characterized at the molecular level, which might be important to identify recurrent alterations and to analyze the molecular mechanisms underlying these mutational events. Probands from a cohort of Lynch Syndrome families were screened for point mutation in MMR genes, subsequently the MLPA assay was used for LGR screening. The identified MLPA alteration was confirmed by cDNA, CGH-microarrays or massive parallel sequencing. In this study, we have delimited the region of 11 LGRs variants on MSH2 locus. Six of them were fully characterized the breakpoints and 9 of them were considered pathogenic. According to our data, LGR on MSH2 locus constituted the 10.8% (9 out of 83 of pathogenic germline alterations found in LS. The frequency of colorectal cancer (CRC and endometrial cancer (EC in LGR carriers was 55% and 11% respectively. Analysis of the breakpoint sequences revealed that in 3 cases, deletions appeared to originate from Alu-mediated recombination events. In the remaining cases, sequence alignment failed to detect microhomology around the breakpoints. The present study provides knowledge on the molecular characterization of MSH2 LGRs, which may have important implications in LS diagnosis and Genetic Counseling. In addition, our data suggests that nonhomologous events would be more frequently involved in the etiology of MSH2 LGRs than expected.

  19. LAF4, an AF4-related gene, is fused to MLL in infant acute lymphoblastic leukemia

    NARCIS (Netherlands)

    von Bergh, ARM; Beverloo, HB; Rombout, P; van Wering, ER; van Weel, MH; Beverstock, GC; Kluin, PM; Slater, RM; Schuuring, E

    2002-01-01

    Infant acute lymphoblastic leukemia (ALL) with MLL gene rearrangements is characterized by a proB phenotype and a poor clinical outcome. We analyzed an infant proB ALL with t(2; 11)(p 15;p 14) and an MLL rearrangement on Southern blot analysis, Rapid amplification of cDNA ends-polymerase chain react

  20. Autosomal rearrangement in Gryllus assimilis Fabricius, 1775 (Orthoptera, Gryllidae

    Directory of Open Access Journals (Sweden)

    Edison Zefa

    1999-09-01

    Full Text Available Gryllus assimilis L. has a karyotype of 2n = 29 (X0, male and 30 (XX, female. The above karyotype was encountered along with another in which 2n = 28 (X0, male and 2n = 29 (XX, female in a population from the outskirts of Rio Claro city (São Paulo State, Brazil. Of eight specimens studied, five had the heterozygous karyotype involving a translocation and three had the basic karyotype. There were no individuals homozygous for the rearrangement. The heterozygous karyotype was the result of a chromosomal rearrangement between chromosome pairs 6 and 10, both of which were initially submetacentric. The members of the sixth pair normally have two constrictions in the small arm, with a satellite at the chromosome tip. The chromosome of the tenth pair involved in the translocation was generally submetacentric and probably underwent a pericentric inversion which transported the centromere to a subterminal position before being translocated. In this case, the long arm of the inverted chromosome of the tenth pair was translocated with the satellite of a member of the sixth pair.A espécie Gryllus assimilis L. apresenta 2n = 29, X0 (macho e 2n = 30, XX (fêmea, porém em alguns indivíduos coletados na cidade de Rio Claro, São Paulo, Brasil, foram encontrados dois cariótipos distintos: o cariótipo básico e outro rearranjado, com 2n = 28, X0 e 2n = 29, XX. O rearranjo foi interpretado como sendo autossômico e heterozigoto, caracterizado pela translocação envolvendo dois pares de homólogos submetacêntricos: o par 10, que possivelmente tem um dos elementos com uma inversão pericêntrica, e o par 6, que possui em seu braço curto duas constrições secundárias, diferenciando satélites em suas extremidades.

  1. DNA rearrangement has occurred in the carbazole-degradative plasmid pCAR1 and the chromosome of its unsuitable host, Pseudomonas fluorescens Pf0-1.

    Science.gov (United States)

    Shintani, Masaki; Matsumoto, Takashi; Yoshikawa, Hirofumi; Yamane, Hisakazu; Ohkuma, Moriya; Nojiri, Hideaki

    2011-12-01

    The carbazole-degradative plasmid pCAR1 carries the class II transposon Tn4676, which contains the car and ant genes, essential for conversion of carbazole into anthranilate, and anthranilate into catechol, respectively. In our previous study, DNA rearrangements in pCAR1 were frequently detected in the host Pseudomonas fluorescens Pf0-1 in the presence of carbazole, resulting in the improvement of host survivability. Several Pf0-1 mutants harbouring pCAR1 were isolated, and deletion of DNA in the plasmid ant gene was found. Here, we compared genome sequences of the parent strain Pf0-1L(pCAR1::rfp) and one of its mutants, 5EP83, to assess whether other DNA rearrangements occurred in either the plasmid or the host chromosome. We found transposition of Tn4676 into the 5EP83 chromosome. In addition, ISPre1 had transposed into the car gene intergenic region on the pCAR1-derivative plasmid of 5EP83, which inhibited car transcription. As a result of these transpositions, 5EP83 was able to metabolize carbazole due to the Tn4676 on its chromosome, although the car genes on its plasmid were non-functional. We also found that one copy of duplicate carAa genes had been deleted, and that ISPre4 had transposed into both the host chromosome and the plasmid. Our findings suggest that Pf0-1 harbouring pCAR1 is subjected to DNA rearrangements not only on the plasmid but also on its chromosome in the presence of carbazole.

  2. Economic Analysis of Alternative Strategies for Detection of ALK Rearrangements in Non Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Shivang Doshi

    2016-01-01

    Full Text Available Identification of alterations in ALK gene and development of ALK-directed therapies have increased the need for accurate and efficient detection methodologies. To date, research has focused on the concordance between the two most commonly used technologies, fluorescent in situ hybridization (FISH and immunohistochemistry (IHC. However, inter-test concordance reflects only one, albeit important, aspect of the diagnostic process; laboratories, hospitals, and payors must understand the cost and workflow of ALK rearrangement detection strategies. Through literature review combined with interviews of pathologists and laboratory directors in the U.S. and Europe, a cost-impact model was developed that compared four alternative testing strategies—IHC only, FISH only, IHC pre-screen followed by FISH confirmation, and parallel testing by both IHC and FISH. Interviews were focused on costs of reagents, consumables, equipment, and personnel. The resulting model showed that testing by IHC alone cost less ($90.07 in the U.S., $68.69 in Europe than either independent or parallel testing by both FISH and IHC ($441.85 in the U.S. and $279.46 in Europe. The strategies differed in cost of execution, turnaround time, reimbursement, and number of positive results detected, suggesting that laboratories must weigh the costs and the clinical benefit of available ALK testing strategies.

  3. Economic Analysis of Alternative Strategies for Detection of ALK Rearrangements in Non Small Cell Lung Cancer.

    Science.gov (United States)

    Doshi, Shivang; Ray, David; Stein, Karen; Zhang, Jie; Koduru, Prasad; Fogt, Franz; Wellman, Axel; Wat, Ricky; Mathews, Charles

    2016-01-01

    Identification of alterations in ALK gene and development of ALK-directed therapies have increased the need for accurate and efficient detection methodologies. To date, research has focused on the concordance between the two most commonly used technologies, fluorescent in situ hybridization (FISH) and immunohistochemistry (IHC). However, inter-test concordance reflects only one, albeit important, aspect of the diagnostic process; laboratories, hospitals, and payors must understand the cost and workflow of ALK rearrangement detection strategies. Through literature review combined with interviews of pathologists and laboratory directors in the U.S. and Europe, a cost-impact model was developed that compared four alternative testing strategies-IHC only, FISH only, IHC pre-screen followed by FISH confirmation, and parallel testing by both IHC and FISH. Interviews were focused on costs of reagents, consumables, equipment, and personnel. The resulting model showed that testing by IHC alone cost less ($90.07 in the U.S., $68.69 in Europe) than either independent or parallel testing by both FISH and IHC ($441.85 in the U.S. and $279.46 in Europe). The strategies differed in cost of execution, turnaround time, reimbursement, and number of positive results detected, suggesting that laboratories must weigh the costs and the clinical benefit of available ALK testing strategies. PMID:26838801

  4. Uncovering potential downstream targets of oncogenic GRPR overexpression in prostate carcinomas harboring ETS rearrangements.

    Science.gov (United States)

    Santos, Joana; Mesquita, Diana; Barros-Silva, João D; Jerónimo, Carmen; Henrique, Rui; Morais, António; Paulo, Paula; Teixeira, Manuel R

    2015-01-01

    Gastrin-releasing peptide receptor (GRPR) is known to be overexpressed in several human malignancies, including prostate cancer, and has been implicated in multiple important neoplastic signaling pathways. We recently have shown that GRPR is an ERG and ETV1 target gene in prostate cancer, using a genome-wide scale and exon-level expression microarray platform. Due to its cellular localization, the relevance of its function and the availability of blocking agents, GRPR seems to be a promising candidate as therapeutic target. Our present work shows that effective knockdown of GRPR in LNCaP and VCaP cells attenuates their malignant phenotype by decreasing proliferation, invasion and anchorage-independent growth, while increasing apoptosis. Using an antibody microarray we were able to validate known and identify new targets of GRPR pathway, namely AKT1, PKCε, TYK2 and MST1. Finally, we show that overexpression of these GRPR targets is restricted to prostate carcinomas harboring ERG and/or ETV1 rearrangements, establishing their potential as therapeutic targets for these particular molecular subsets of the disease. PMID:26097883

  5. Recurrent SKIL-activating rearrangements in ETS-negative prostate cancer.

    Science.gov (United States)

    Annala, Matti; Kivinummi, Kati; Tuominen, Joonas; Karakurt, Serdar; Granberg, Kirsi; Latonen, Leena; Ylipää, Antti; Sjöblom, Liisa; Ruusuvuori, Pekka; Saramäki, Outi; Kaukoniemi, Kirsi M; Yli-Harja, Olli; Vessella, Robert L; Tammela, Teuvo L J; Zhang, Wei; Visakorpi, Tapio; Nykter, Matti

    2015-03-20

    Prostate cancer is the third most common cause of male cancer death in developed countries, and one of the most comprehensively characterized human cancers. Roughly 60% of prostate cancers harbor gene fusions that juxtapose ETS-family transcription factors with androgen regulated promoters. A second subtype, characterized by SPINK1 overexpression, accounts for 15% of prostate cancers. Here we report the discovery of a new prostate cancer subtype characterized by rearrangements juxtaposing the SMAD inhibitor SKIL with androgen regulated promoters, leading to increased SKIL expression. SKIL fusions were found in 6 of 540 (1.1%) prostate cancers and 1 of 27 (3.7%) cell lines and xenografts. 6 of 7 SKIL-positive cancers were negative for ETS overexpression, suggesting mutual exclusivity with ETS fusions. SKIL knockdown led to growth arrest in PC-3 and LNCaP cell line models of prostate cancer, and its overexpression led to increased invasiveness in RWPE-1 cells. The role of SKIL as a prostate cancer oncogene lends support to recent studies on the role of TGF-β signaling as a rate-limiting step in prostate cancer progression. Our findings highlight SKIL as an oncogene and potential therapeutic target in 1-2% of prostate cancers, amounting to an estimated 10,000 cancer diagnoses per year worldwide.

  6. Variation induced by DNA rearrangement in a transgenic Bt+CpTI cotton strain

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    In the development of transgenic Bt + CpTI cotton cultivars, one male and female sterile mutant has been found in a homozygous T4 strain in our laboratory. The mutant plant, as well as its leaves, buds and flowers, is only 1/2-1/3 as large as that of the wild transgenic Bt + CpTI bivalant cotton plants. Cytological observation found that the chromosome number of the mutant is 2n = 52; however, there are 4 - 8 univalents observed in meiosis Ⅰ of pollen mother cells. Laboratory bioassay indicated that the mutant was highly resistant to bollworm as the wild plants. PCR amplification revealed that Bt and CpTI genes in the mutant were still intactly inserted. However, small deletion of flanked area had been observed in the mutant by Southern blotting analysis. So it is proposed that the mutant phenotype might result from either the DNA deletion or T-DNA trans-ferring in plant genome. No such report has been presented that the rearrangement of chromosome structure in a homo-zygous transgenic line occurred. Further analysis is ongoing.

  7. Comparative mitochondrial genome analysis reveals the evolutionary rearrangement mechanism in Brassica.

    Science.gov (United States)

    Yang, J; Liu, G; Zhao, N; Chen, S; Liu, D; Ma, W; Hu, Z; Zhang, M

    2016-05-01

    The genus Brassica has many species that are important for oil, vegetable and other food products. Three mitochondrial genome types (mitotype) originated from its common ancestor. In this paper, a B. nigra mitochondrial main circle genome with 232,407 bp was generated through de novo assembly. Synteny analysis showed that the mitochondrial genomes of B. rapa and B. oleracea had a better syntenic relationship than B. nigra. Principal components analysis and development of a phylogenetic tree indicated maternal ancestors of three allotetraploid species in Us triangle of Brassica. Diversified mitotypes were found in allotetraploid B. napus, in which napus-type B. napus was derived from B. oleracea, while polima-type B. napus was inherited from B. rapa. In addition, the mitochondrial genome of napus-type B. napus was closer to botrytis-type than capitata-type B. oleracea. The sub-stoichiometric shifting of several mitochondrial genes suggested that mitochondrial genome rearrangement underwent evolutionary selection during domestication and/or plant breeding. Our findings clarify the role of diploid species in the maternal origin of allotetraploid species in Brassica and suggest the possibility of breeding selection of the mitochondrial genome. PMID:27079962

  8. Multiple forms of atypical rearrangements generating supernumerary derivative chromosome 15

    Directory of Open Access Journals (Sweden)

    Sigman Marian

    2008-01-01

    Full Text Available Abstract Background Maternally-derived duplications that include the imprinted region on the proximal long arm of chromosome 15 underlie a complex neurobehavioral disorder characterized by cognitive impairment, seizures and a substantial risk for autism spectrum disorders1. The duplications most often take the form of a supernumerary pseudodicentric derivative chromosome 15 [der(15] that has been called inverted duplication 15 or isodicentric 15 [idic(15], although interstitial rearrangements also occur. Similar to the deletions found in most cases of Angelman and Prader Willi syndrome, the duplications appear to be mediated by unequal homologous recombination involving low copy repeats (LCR that are found clustered in the region. Five recurrent breakpoints have been described in most cases of segmental aneuploidy of chromosome 15q11-q13 and previous studies have shown that most idic(15 chromosomes arise through BP3:BP3 or BP4:BP5 recombination events. Results Here we describe four duplication chromosomes that show evidence of atypical recombination events that involve regions outside the common breakpoints. Additionally, in one patient with a mosaic complex der(15, we examined homologous pairing of chromosome 15q11-q13 alleles by FISH in a region of frontal cortex, which identified mosaicism in this tissue and also demonstrated pairing of the signals from the der(15 and the normal homologues. Conclusion Involvement of atypical BP in the generation of idic(15 chromosomes can lead to considerable structural heterogeneity.

  9. On the Complexity of Rearrangement Problems under the Breakpoint Distance

    CERN Document Server

    Kovac, Jakub

    2011-01-01

    Tannier et al. introduced a generalization of breakpoint distance for multichromosomal genomes. They showed that the median problem under the breakpoint distance is solvable in polynomial time in the multichromosomal circular and mixed models. This is intriguing, since in all other rearrangement models (DCJ, reversal, unichromosomal or multilinear breakpoint models), the problem is NP-hard. The complexity of the small or even the large phylogeny problem under the breakpoint distance remained an open problem. We improve the algorithm for the median problem and show that it is equivalent to the problem of finding maximum cardinality non-bipartite matching (under linear reduction). On the other hand, we prove that the more general small phylogeny problem is NP-hard. Surprisingly, we show that it is already NP-hard (or even APX-hard) for 4 species (a quartet phylogeny). In other words, while finding an ancestor for 3 species is easy, already finding two ancestors for 4 species is hard. We also show that, in the u...

  10. Structural rearrangement through lanthanide contraction in dinuclear complexes.

    Science.gov (United States)

    Hutchings, Amy-Jayne; Habib, Fatemah; Holmberg, Rebecca J; Korobkov, Ilia; Murugesu, Muralee

    2014-02-17

    A new series of lanthanide complexes was synthesized, and the geometry and preliminary magnetic measurements of the complexes were explored. The specific ligand used (N'-(2-hydroxy-3-methoxybenzylidene)benzhydrazide) (H2hmb) was synthesized using a Schiff-base approach and was employed due to the presence of a coordination pocket that is able to accommodate magnetically selective lanthanide ions. The series can be divided into two groups that are categorized by a drastic structural rearrangement. The first group, Type I, contains six analogous complexes with the formula [M(III)2(Hhmb)3(NCS)3]·2MeOH·py (M = Y 1, Eu 2, Gd 3, Tb 4, Dy 5, Ho 6), while the second group, Type II, contains two dinuclear complexes with formula [M(III)2(Hhmb)2(NCS)4(MeOH)2] (M = Er 7, and Yb 8). Single-crystal X-ray analysis revealed that all M(III) ions in Type I exhibit monocapped distorted square antiprismatic geometries, while those of Type II exhibit distorted dodecahedron geometry. The direct current and alternating current magnetic measurements were carried out on all complexes, with 5, 7, and 8 exhibiting slow relaxation of the magnetization under an applied optimum dc field. Furthermore, complex 8 is the first example of a dinuclear Yb-based single-molecule magnet showing field-dependent multiple relaxation processes. PMID:24499030

  11. Chromosome painting defines genomic rearrangements between red howler monkey subspecies.

    Science.gov (United States)

    Consigliere, S; Stanyon, R; Koehler, U; Agoramoorthy, G; Wienberg, J

    1996-06-01

    We hybridized whole human chromosome-specific DNA libraries to chromosomes of two supposed subspecies of Alouatta seniculus: Alouatta seniculus sara and Alouatta seniculus arctoides. The number of hybridization signals per haploid set is 42 in A. s. sara and 43 in A. s. arctoidea; the two karyotypes differ by at least 16 chromosomal rearrangements, including numerous translocations. An unusual sex chromosome system is shared by both taxa. The sex chromosome system results from a Y translocation with a chromosome homologous to parts of human chromosome 3/15 and can be described as X1X2Y1Y2/X1X1X2X2 (male/female). Both red howlers also have microchromosomes, a highly unusual karyological trait not found in other higher primates. These microchromosomes are not hybridized by any human chromosome paint and therefore are probably composed of repetitive DNA. It is well known that New World monkeys have high karyological variability. It is probable that molecular cytogenetic analyses including chromosome painting will permit an accurate reconstruction of the phylogeny of these monkeys and help establish the ancestral karyotype for higher primates. PMID:8817065

  12. Measuring soil layer thickness in land rearrangement with GPR data

    International Nuclear Information System (INIS)

    Accurate measurement of soil layer thickness by GPR (ground penetrating radar) is of great importance for overlay design and quality control/quality assurance for land rearrangement projects. Soil layer detection is complex because of multiple reflections and high attenuation for electromagnetic (EM) waves propagating in the soil media. This paper proposes a novel data processing method based on the reflection and refraction of the EM waves to improve the measurement accuracy. A cross-correlation sequence is introduced to align the traces, and the effects of random noise are reduced by using a forwards and backwards filtering procedure without phase delay. Additionally, the homomorphic deconvolution, namely the power cepstrum, is employed to deconvolve GPR data and, thus, to enhance its interface reflection. The results of the verification test show that the measurement can achieve high accuracy, with an error less than 10%, and the measurement performance is greatly improved by using the new method. Finally, a contour map of the research area is generated automatically for quality detection and quality control guidance. (paper)

  13. Engineering prokaryotic gene circuits

    OpenAIRE

    Michalodimitrakis, Konstantinos; Isalan, Mark

    2009-01-01

    Engineering of synthetic gene circuits is a rapidly growing discipline, currently dominated by prokaryotic transcription networks, which can be easily rearranged or rewired to give different output behaviours. In this review, we examine both a rational and a combinatorial design of such networks and discuss progress on using in vitro evolution techniques to obtain functional systems. Moving beyond pure transcription networks, more and more networks are being implemented at the level of RNA, t...

  14. Organization and expression of immunoglobulin genes in fetal liver hybridomas.

    Science.gov (United States)

    Perry, R P; Kelley, D E; Coleclough, C; Kearney, J F

    1981-01-01

    The organization and expression of immunoglobulin genes were studied in a series of six hybridomas derived from the fusion of a nonproducing myeloma cell with cells from mouse fetal liver. These hybridomas, which exhibit several phenotypic characteristics of immature B lymphocytes, all have productively rearranged mu heavy chain genes and produce both the membrane and secreted forms of mu mRNA in a ratio of about 1:10. Significantly, none of the hybridomas has an unrearranged (germ line) allelic mu gene. Examination of the kappa light chain genes revealed that all six of the hybridomas contain unrearranged kappa loci and produce 8.4-kilobase transcripts containing kappa constant region sequences. None of the five hybridomas that exhibit a mu-only phenotype contains a rearranged kappa gene other than that derived from the myeloma parent. One hybridoma, which actively secretes kappa immunoglobulin, contains a rearranged kappa gene of fetal liver origin and synthesizes a distinctive kappa mRNA precursor in addition to the 8.4-kilobase transcript. These results demonstrate that rearrangement of heavy chain immunoglobulin genes normally occurs prior to that of light chain genes and further indicate that the transcriptional competence of the kappa constant region locus is established prior to the time of its rearrangement.

  15. Ovarian Hemangiomas Do Not Harbor EWSR1 Rearrangements: Clinicopathologic Characterization of 10 Cases.

    Science.gov (United States)

    Schoolmeester, John Kenneth; Greipp, Patricia T; Keeney, Gary L; Soslow, Robert A

    2015-09-01

    rearrangement; however, 2 cases demonstrated additional intact copies of EWSR1 indicating aneusomy 22 or a structural abnormality of chromosome 22 resulting in apparent duplication of the EWSR1 gene region (at 22q12). Although an uncommon entity, awareness of ovarian hemangioma's unique and diverse clinical presentation as well as its potential to radiologically imitate malignant ovarian neoplasms are important. PMID:25851709

  16. Gas-phase Smiles Rearrangement of Sulfonylurea Herbicides in Electrospray Ionization Mass Spectrometry

    Institute of Scientific and Technical Information of China (English)

    张佳; 柴云峰; 王伟; 尚伟; 潘远江

    2012-01-01

    In the negative ion mode of electrospray ionization tandem mass spectrometry (ES1-MS/MS) of four sulfonyl- urea herbicides, Smiles rearrangements were observed in rimsulfuron and nicosulfuron. In the case of rimsulfuron, two competitive gas-phase Smiles rearrangements initiated by nitrogen anion and oxygen anion respectively were witnessed. The ion-neutral complex was proposed as the reactive intermediate in the course of this unimoleeular dissociation reaction of the oxygen attack Smiles rearrangement route. The density functional theory (DFT) was carried out to elucidate the mechanism as well as to show the possible transition states and the intermediates.

  17. Anisotropic rearrangement of the substrate atoms during Ar bombardment on Pd(0 0 1) surface

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sang-Pil [Computational Science Center, Interdisciplinary Fusion Technology Division, Korea Institute of Science and Technology, Seoul 136-791 (Korea, Republic of); Kim, Byung-Hyun [Computational Science Center, Interdisciplinary Fusion Technology Division, Korea Institute of Science and Technology, Seoul 136-791 (Korea, Republic of); Department of Materials Science and Engineering, Hanyang University, Seoul 133-791 (Korea, Republic of); Kim, Haeri [Computational Science Center, Interdisciplinary Fusion Technology Division, Korea Institute of Science and Technology, Seoul 136-791 (Korea, Republic of); Department of Physics, Ewha Womans University, Seoul 120-750 (Korea, Republic of); Lee, Kwang-Ryeol, E-mail: krlee@kist.re.kr [Computational Science Center, Interdisciplinary Fusion Technology Division, Korea Institute of Science and Technology, Seoul 136-791 (Korea, Republic of); Chung, Yong-Chae [Department of Materials Science and Engineering, Hanyang University, Seoul 133-791 (Korea, Republic of); Seo, Jikeun [Department of Ophthalmic Optics, Chodang University, Muan 534-701 (Korea, Republic of); Kim, Jae-Sung [Department of Physics, Sookmyung Women' s University, Seoul 140-742 (Korea, Republic of)

    2011-11-01

    Using a three-dimensional molecular dynamics (MD) simulation, we investigated the atomic scale rearrangement that occurs on a Pd(0 0 1) surface after energetic bombardment by Ar at room temperature. High energy Ar bombardment provoked the significant rearrangement of Pd atoms in a ballistic manner with a fourfold symmetric lateral distribution aligned along the <1 1 0> direction. The MD simulation of uniform Ar bombardment at normal incidence on a Pd surface reproduced the experimentally observed fourfold symmetric nano-scale surface structure. The present result supports that the ballistic rearrangement of the substrate atoms plays an important role in the ion induced surface structure evolution.

  18. Molecular diagnosis in early mycosis fungoides using T-cell receptor gene rearrangement by laser capture microdissection and genescan%早期蕈样肉芽肿采用激光捕获显微切割及基因扫描分子诊断基因重排的研究

    Institute of Scientific and Technical Information of China (English)

    张凡; 涂平; 卜定方; 武玲慎

    2010-01-01

    目的:研究激光捕获显微切割及基因扫描定性检测T细胞受体(TCR)_γ基因重排在早期蕈样肉芽肿(MF)细胞中表达的可行性.方法:激光捕获显微切割(laser capture microdissection,LCM)分离早期MF中的肿瘤细胞,荧光标记引物双重聚合酶链反应(PCR)和基因扫描(GeneScan)分析TCR _γ基因重排.结果:9例早期MF的TCR_γ/基因重排检出率为66.7%(6/9).2例肿瘤期MF的检出率为100%.结论:激光捕获显微切割技术可用于诊断早期MF的TCR_γ基凶重排检测.

  19. The complete mitochondrial genome of the sexual oribatid mite Steganacarus magnus: genome rearrangements and loss of tRNAs

    Directory of Open Access Journals (Sweden)

    Cameron Stephen L

    2008-11-01

    Full Text Available Abstract Background Complete mitochondrial (mt genomes and the gene rearrangements therein are increasingly used as molecular markers for investigating phylogenetic relationships, especially for elucidating deep splits. Contributing to the complete mt genomes of arthropods, especially Arachnida, available so far, we provide the first complete mt genome of a sarcoptiform mite species, the sexually reproducing oribatid mite Steganacarus magnus (Acari, Oribatida which was determined by sequencing of long PCR products. Results The mt genome of S. magnus lacks 16 tRNAs, only those for leucine, histidine, proline, tryptophan, glutamine and serine are present. Within those tRNAs only tRNA-His and tRNA-Pro have kept their original position, the others are translocated. Furthermore, the mt genome of S. magnus consists of 13,818 bp and it is composed of 13 protein-coding genes and two genes for the ribosomal RNA subunits that are typically found in metazoan mt genomes. The gene order in S. magnus differs from the hypothetical ancestral chelicerate arrangement as conserved in Limulus polyphemus: instead of nad1-rrnL-rrnS-LNR-nad2 (tRNAs excluded S. magnus is nad2-rrnL-nad1-rrnS-LNR. Phylogenetic analyses of a concatenated amino acid dataset of all mt protein-coding genes of 28 arthropod species suggest a sister-group relationship of sarcoptiform and prostigmatid mites (S. magnus and Leptotrombidium. Conclusion The mt gene arrangement of S. magnus differs from the hypothetical ground plan of arthropods and from that of other mites further contributing to the variety of mt gene arrangements found in Arachnida. The unexpected lack of tRNAs is enigmatic, probably showing that the loss of mt genes is an ongoing evolutionary process. For solving phylogenetic relationships of oribatid mite lineages and their position within Acari further complete mt genomes are needed.

  20. An efficient algorithm for the contig ordering problem under algebraic rearrangement distance.

    Science.gov (United States)

    Lu, Chin Lung

    2015-11-01

    Assembling a genome from short reads currently obtained by next-generation sequencing techniques often results in a collection of contigs, whose relative position and orientation along the genome being sequenced are unknown. Given two sets of contigs, the contig ordering problem is to order and orient the contigs in each set such that the genome rearrangement distance between the resulting sets of ordered and oriented contigs is minimized. In this article, we utilize the permutation groups in algebra to propose a near-linear time algorithm for solving the contig ordering problem under algebraic rearrangement distance, where the algebraic rearrangement distance between two sets of ordered and oriented contigs is the minimum weight of applicable rearrangement operations required to transform one set into the other. PMID:26247343

  1. Unexpected Stereospecific Rearrangement-Addition Reaction of Trisubstituted Gibberellin Epoxides with Trimethylaluminium

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    A novel rearrangement-addition reaction of trisubstituted gibberellin epoxides with trimethylaluminium is reported. The reaction proceeds stereospecifically to give tertiary methyl alcohols. The possible mechanism for the reaction is also discussed.

  2. High levels of nuclear MYC protein predict the presence of MYC rearrangement in diffuse large B-cell lymphoma

    DEFF Research Database (Denmark)

    Green, Tina Marie; Nielsen, Ole; de Stricker, Karin;

    2012-01-01

    Determining the presence of MYC gene rearrangements is becoming an increasingly important part of the diagnostic workup in aggressive lymphoma. Cytogenetic MYC alterations aid in differentiating diffuse large B-cell lymphoma (DLBCL) from Burkitt lymphoma. In addition, MYC aberrations are associated...... with poor prognosis in DLBCL. Fluorescence in situ hybridization and karyotyping are standard tests for detecting MYC aberrations, but these techniques are laborious and expensive. Here, we studied MYC status of 219 DLBCLs and Burkitt lymphomas using fluorescence in situ hybridization, immunohistochemistry......, and quantitative real-time polymerase chain reaction (QRT-PCR). Overall, 15% of the cases had an MYC break. QRT-PCR analysis of MYC expression showed that 72% of DLBCLs with an MYC break had aberrantly high or low levels of MYC transcript. Excluding the cases with aberrantly low MYC expression, we found...

  3. DNA modifications and genome rearrangements during the development and sex differentiation of the bumble bee Bombus terrestris.

    Science.gov (United States)

    Bigot, Y; Jegot, G; Casteret, S; Aupinel, P; Tasei, J-N

    2011-04-01

    Bombus terrestris is a bumble bee that, like most hymenopteran species, exhibits ploidy-specific sex determination controlled by a single sex gene. Depending on their ploidy and the queen pheromone repression, the imagoes differentiate into three castes: males, workers and queens. Here, we focus on the differences of genome organization that occur during development and sex differentiation. We found that cytosine methylation is a significant epigenetic factor with profiles that can be correlated with both processes. We also showed that two kinds of genomic rearrangement occur. The first consists of important DNA amplifications that have sequence profiles that differ in the different developmental instars and sexes. In the second kind, DNA losses also occur, at least involving the mosaic transposable element B. terrestris mosaic repeat 1 (BTMR1).

  4. The Complete Chloroplast Genome Sequence of a Relict Conifer Glyptostrobus pensilis: Comparative Analysis and Insights into Dynamics of Chloroplast Genome Rearrangement in Cupressophytes and Pinaceae

    Science.gov (United States)

    Zheng, Renhua; Xu, Haibin; Zhou, Yanwei; Li, Meiping; Lu, Fengjuan; Dong, Yini; Liu, Xin; Chen, Jinhui; Shi, Jisen

    2016-01-01

    Glyptostrobus pensilis, belonging to the monotypic genus Glyptostrobus (Family: Cupressaceae), is an ancient conifer that is naturally distributed in low-lying wet areas. Here, we report the complete chloroplast (cp) genome sequence (132,239 bp) of G. pensilis. The G. pensilis cp genome is similar in gene content, organization and genome structure to the sequenced cp genomes from other cupressophytes, especially with respect to the loss of the inverted repeat region A (IRA). Through phylogenetic analysis, we demonstrated that the genus Glyptostrobus is closely related to the genus Cryptomeria, supporting previous findings based on physiological characteristics. Since IRs play an important role in stabilize cp genome and conifer cp genomes lost different IR regions after splitting in two clades (cupressophytes and Pinaceae), we performed cp genome rearrangement analysis and found more extensive cp genome rearrangements among the species of cupressophytes relative to Pinaceae. Additional repeat analysis indicated that cupressophytes cp genomes contained less potential functional repeats, especially in Cupressaceae, compared with Pinaceae. These results suggested that dynamics of cp genome rearrangement in conifers differed since the two clades, Pinaceae and cupressophytes, lost IR copies independently and developed different repeats to complement the residual IRs. In addition, we identified 170 perfect simple sequence repeats that will be useful in future research focusing on the evolution of genetic diversity and conservation of genetic variation for this endangered species in the wild. PMID:27560965

  5. Complex chromosome rearrangements related 15q14 microdeletion plays a relevant role in phenotype expression and delineates a novel recurrent syndrome

    Directory of Open Access Journals (Sweden)

    Tomaiuolo Anna

    2011-04-01

    Full Text Available Abstract Complex chromosome rearrangements are constitutional structural rearrangements involving three or more chromosomes or having more than two breakpoints. These are rarely seen in the general population but their frequency should be much higher due to balanced states with no phenotypic presentation. These abnormalities preferentially occur de novo during spermatogenesis and are transmitted in families through oogenesis. Here, we report a de novo complex chromosome rearrangement that interests eight chromosomes in eighteen-year-old boy with an abnormal phenotype consisting in moderate developmental delay, cleft palate, and facial dysmorphisms. Standard G-banding revealed four apparently balanced traslocations involving the chromosomes 1;13, 3;19, 9;15 and 14;18 that appeared to be reciprocal. Array-based comparative genomic hybridization analysis showed no imbalances at all the breakpoints observed except for an interstitial microdeletion on chromosome 15. This deletion is 1.6 Mb in size and is located at chromosome band 15q14, distal to the Prader-Willi/Angelman region. Comparing the features of our patient with published reports of patients with 15q14 deletion this finding corresponds to the smallest genomic region of overlap. The deleted segment at 15q14 was investigated for gene content.

  6. Chromosomal rearrangements as the cause of habitual abortions

    Directory of Open Access Journals (Sweden)

    Petrović Bojana

    2007-01-01

    Full Text Available Introduction Habitual abortion is a spontaneous abortion occurring in three or more successive pregnancies with no intervening pregnancies. Chromosomal aberrations account for approximately 50% of fetal losses prior to 15 weeks. Objective The aim of this study was to determine the role of chromosomal rearrangements in etiology of habitual abortions in couples with a normal karyotype. Method We analyzed the karyotype of placental tissue, taken from spontaneously aborted fetuses from couples with normal karyotype and habitual abortions. The women tested were divided into two groups. In the first group, there were 23 women below 35, and in the second, 13 women above 35 years of age. Tissue samples were obtained from the abortions and processed using standard techniques. All specimens were G-banded using trypsin-Giemsa stain. Sixteen metaphase cells were analyzed for their chromosome constitution in each sample. For statistical analysis, we used χІ test. Results From 36 analyzed cases, there were 17 (47.2% with an abnormal chromosomal constitution and 19 (58.2% with a normal chromosomal constitution. Trisomy 16 was detected in 4 cases. Among sex chromosomal aberrations, only monosomy X was found in 3 cases. Two cases of triploidy and two cases of trisomy 8, 18 and 21 were detected. Trisomy 12 and trisomy 13 were found in one case each. In group of women under 35 (I group, the percentage of chromosomally abnormal fetuses was 34.8%, while in the group of women above 35 (II group, that percentage was 69.2, but there was no statistically significant difference between groups I and II (χІ=3.01< χІ(1 and 0.05=3.841. Conclusion Hereditary base defects are a significant cause of spontaneous abortions in early pregnancy. Detection of chromosomal abnormalities provides the opportunity to plan further treatment of reproduction disorders.

  7. Mycoreovirus genome alterations: similarities to and differences from rearrangements reported for other reoviruses.

    Science.gov (United States)

    Tanaka, Toru; Eusebio-Cope, Ana; Sun, Liying; Suzuki, Nobuhiro

    2012-01-01

    The family Reoviridae is one of the largest virus families with genomes composed of 9-12 double-stranded RNA segments. It includes members infecting organisms from protists to humans. It is well known that reovirus genomes are prone to various types of genome alterations including intragenic rearrangement and reassortment under laboratory and natural conditions. Recently distinct genetic alterations were reported for members of the genus Mycoreovirus, Mycoreovirus 1 (MyRV1), and MyRV3 with 11 (S1-S11) and 12 genome segments (S1-S12), respectively. While MyRV3 S8 is lost during subculturing of infected host fungal strains, MyRV1 rearrangements undergo alterations spontaneously and inducibly. The inducible MyRV1 rearrangements are different from any other previous examples of reovirus rearrangements in their dependence on an unrelated virus factor, a multifunctional protein, p29, encoded by a distinct virus Cryphonectria parasitica hypovirus 1 (CHV1). A total of 5 MyRV1 variants with genome rearranged segments (S1-S3, S6 and S10) are generated in the background of a single viral strain in the presence of CHV1 p29 supplied either transgenically or by coinfection. MyRV1 S4 and S10 are rearranged, albeit very infrequently, in a CHV1 p29 independent fashion. A variant of MyRV1 with substantial deletions in both S4 and S10, generated through a combined reassortment and rearrangement approach, shows comparable replication levels to the wild-type MyRV1. In vivo and in vitro interactions of CHV1 p29 and MyRV1 VP9 are implicated in the induction of MyRV1 rearrangements. However, the mechanism underlying p29-mediated rearrangements remains largely unknown. MyRV1 S4 rearrangements spontaneously occurred independently of CHV1 p29. In the absence of reverse genetics systems for mycoreoviruses, molecular and biological characterization of these MyRV1 and MyRV3 variants contribute to functional analyses of the protein products encoded by those rearranged segments.

  8. A novel RET rearrangement (ACBD5/RET) by pericentric inversion, inv(10)(p12.1;q11.2), in papillary thyroid cancer from an atomic bomb survivor exposed to high-dose radiation.

    Science.gov (United States)

    Hamatani, Kiyohiro; Eguchi, Hidetaka; Koyama, Kazuaki; Mukai, Mayumi; Nakachi, Kei; Kusunoki, Yoichiro

    2014-11-01

    During analysis of RET/PTC rearrangements in papillary thyroid cancer (PTC) among atomic bomb survivors, a cDNA fragment of a novel type of RET rearrangement was identified in a PTC patient exposed to a high radiation dose using the improved 5' RACE method. This gene resulted from the fusion of the 3' portion of RET containing tyrosine kinase domain to the 5' portion of the acyl-coenzyme A binding domain containing 5 (ACBD5) gene, by pericentric inversion inv(10)(p12.1;q11.2); expression of the fusion gene was confirmed by RT-PCR. ACBD5 gene is ubiquitously expressed in various human normal tissues including thyroid. Full-length cDNA of the ACBD5-RET gene was constructed and then examined for tumorigenicity. Enhanced phosphorylation of ERK proteins in the MAPK pathway was observed in NIH3T3 cells transfected with expression vector encoding the full-length ACBD5/RET cDNA, while this was not observed in the cells transfected with empty expression vector. Stable NIH3T3 transfectants with ACBD5-RET cDNA induced tumor formation after their injection into nude mice. These findings suggest that the ACBD5-RET rearrangement is causatively involved in the development of PTC. PMID:25175022

  9. Complete sequences of the highly rearranged molluscan mitochondrial genomes of the scaphopod graptacme eborea and the bivalve mytilus edulis

    Energy Technology Data Exchange (ETDEWEB)

    Boore, Jeffrey L.; Medina, Monica; Rosenberg, Lewis A.

    2004-01-31

    We have determined the complete sequence of the mitochondrial genome of the scaphopod mollusk Graptacme eborea (Conrad, 1846) (14,492 nts) and completed the sequence of the mitochondrial genome of the bivalve mollusk Mytilus edulis Linnaeus, 1758 (16,740 nts). (The name Graptacme eborea is a revision of the species formerly known as Dentalium eboreum.) G. eborea mtDNA contains the 37 genes that are typically found and has the genes divided about evenly between the two strands, but M. edulis contains an extra trnM and is missing atp8, and has all genes on the same strand. Each has a highly rearranged gene order relative to each other and to all other studied mtDNAs. G. eborea mtDNA has almost no strand skew, but the coding strand of M. edulis mtDNA is very rich in G and T. This is reflected in differential codon usage patterns and even in amino acid compositions. G. eborea mtDNA has fewer non-coding nucleotides than any other mtDNA studied to date, with the largest non-coding region being only 24 nt long. Phylogenetic analysis using 2,420 aligned amino acid positions of concatenated proteins weakly supports an association of the scaphopod with gastropods to the exclusion of Bivalvia, Cephalopoda, and Polyplacophora, but is generally unable to convincingly resolve the relationships among major groups of the Lophotrochozoa, in contrast to the good resolution seen for several other major metazoan groups.

  10. SWI/SNF Subunits SMARCA4, SMARCD2 and DPF2 Collaborate in MLL-Rearranged Leukaemia Maintenance.

    Directory of Open Access Journals (Sweden)

    V Adam Cruickshank

    Full Text Available Alterations in chromatin structure caused by deregulated epigenetic mechanisms collaborate with underlying genetic lesions to promote cancer. SMARCA4/BRG1, a core component of the SWI/SNF ATP-dependent chromatin-remodelling complex, has been implicated by its mutational spectrum as exerting a tumour-suppressor function in many solid tumours; recently however, it has been reported to sustain leukaemogenic transformation in MLL-rearranged leukaemia in mice. Here we further explore the role of SMARCA4 and the two SWI/SNF subunits SMARCD2/BAF60B and DPF2/BAF45D in leukaemia. We observed the selective requirement for these proteins for leukaemic cell expansion and self-renewal in-vitro as well as in leukaemia. Gene expression profiling in human cells of each of these three factors suggests that they have overlapping functions in leukaemia. The gene expression changes induced by loss of the three proteins demonstrate that they are required for the expression of haematopoietic stem cell associated genes but in contrast to previous results obtained in mouse cells, the three proteins are not required for the expression of c-MYC regulated genes.

  11. Synthesis of novel boron chelate complexes and proposed mechanism of new rearrangement.

    Science.gov (United States)

    Zhang, Rui-Zhe; Feng, Xiao; Liu, Ying; Wang, Sheng-Qing; Liu, Jin-Ting; Zhao, Bao-Xiang

    2015-03-15

    We synthesized novel boron chelate complexes by the reaction of pyrazoline derivatives and boron trifluoride diethyl etherate followed by a new rearrangement. The structures of the compounds were characterized by IR, NMR and HRMS, especially, a typical compound 3c was confirmed by X-ray single crystal analysis. We proposed a mechanism of the rearrangement. Moreover, the absorption and fluorescence spectroscopy of these compounds were measured.

  12. Expedited Synthesis of Benzofuran-2-Carboxylic Acids via Microwave-Assisted Perkin Rearrangement Reaction

    OpenAIRE

    Marriott, Karla-Sue C.; Bartee, Rena; Morrison, Andrew Z.; Stewart, Leonard; Wesby, Julian

    2012-01-01

    3-Halocoumarins are readily converted into benzofuran-2-carboxylic acids via a Perkin (coumarin-benzofuran ring contraction) rearrangement reaction. This rearrangement entails initial base catalyzed ring fission. The resulting phenoxide anion then attacks a vinyl halide to produce the final benzofuran moiety. We explored this reaction under microwave reaction conditions and were able to significantly reduce reaction times as well as obtain very high yields of a series of benzofuran-2-carboxyl...

  13. Computer study of liquid phase sintering - three-dimensional time dependent rearrangement

    Energy Technology Data Exchange (ETDEWEB)

    Nikolic, Zoran S [University of Nish, Faculty of Electronic Engineering, Department of Microelectronics, 18000 Nish, PO Box 73 (Serbia); Wakai, Fumihiro, E-mail: zoran.nikolic@elfak.ni.ac.rs [Secure Materials Center, Materials and Structures Laboratory, Tokyo Institute of Technology, R3-23 4259 Nagatsuta, Midori, Yokohama, 226-8503 (Japan)

    2011-03-15

    The rearrangement process during liquid phase sintering has been generally accepted that driven by the capillary forces between solid grains embedded in liquid. This paper outlines a computer-based method for three-dimensional computer simulation of rearrangement during liquid phase sintering. The theoretical models dealing with the fundamental interaction forces that exist between grains attached by liquid bridges will be outlined and the development from these pair-wise interactions to multi-grain models will be described.

  14. ETV6 rearrangements are recurrent in myeloid malignancies and are frequently associated with other genetic events.

    Science.gov (United States)

    Haferlach, Claudia; Bacher, Ulrike; Schnittger, Susanne; Alpermann, Tamara; Zenger, Melanie; Kern, Wolfgang; Haferlach, Torsten

    2012-04-01

    ETV6 (TEL) rearrangements are favorable in pediatric acute lymphoblastic leukemia but are less well characterized in myeloid malignancies. We investigated 9,550 patients with myeloid disorders for ETV6 rearrangements by chromosome banding analysis and interphase fluorescence in situ hybridization. ETV6 rearrangements were identified in 51 of 9,550 (0.5%) patients (range, 19.2-85.3 years). Frequencies were in detail: acute myeloid leukemia (AML): 40 of 3,798, 1.1%; myelodysplastic syndromes (MDS): 6 of 3,375, 0.2%; myeloproliferative neoplasms (MPNs): 5 of 1,720, 0.3%; MDS/MPN: 0 of 210; and chronic myelomonocytic leukemia: 0 of 447. Thirty-three different partner bands of ETV6 were identified, and most were recurrent: 3q26 (n = 10), 5q33 (n = 4), 17q11 (n = 3), 22q12 (n = 3), 5q31 (n = 2), and 2q31 (n = 2). Additional chromosomal abnormalities were identified in 29 of 51 (57%) ETV6 rearranged cases. In AML, ETV6 rearrangements were frequently associated with NPM1 (9/39, 23%) and RUNX1 mutations (6/31, 19%). The FAB M0 subtype was more frequent in ETV6 rearranged de novo AML than other AML (P Research Council criteria. Our study confirms the variety of ETV6 rearrangements in AML, MDS, and MPNs often in association with other genetic events. Prognosis of ETV6 rearranged de novo AML seems to be intermediate, which should be independently confirmed. PMID:22162288

  15. Synthesis of Benzofuran Derivatives via Rearrangement and Their Inhibitory Activity on Acetylcholinesterase

    Directory of Open Access Journals (Sweden)

    Ling-Yi Kong

    2010-11-01

    Full Text Available During a synthesis of coumarins to obtain new candidates for treating Alzheimer’s Disease (AD, an unusual rearrangement of a benzopyran group to a benzofuran group occurred, offering a novel synthesis pathway of these benzofuran derivatives. The possible mechanism of the novel rearrangement was also discussed. All of the benzofuran derivatives have weak anti-AChE activities compared with the reference compound, donepezil.

  16. Rearrangement-based phylogeny using the Single-Cut-or-Join operation.

    Science.gov (United States)

    Biller, Priscila; Feijão, Pedro; Meidanis, João

    2013-01-01

    Recently, the Single-Cut-or-Join (SCJ) operation was proposed as a basis for a new rearrangement distance between multichromosomal genomes, leading to very fast algorithms, both in theory and in practice. However, it was not clear how well this new distance fares when it comes to using it to solve relevant problems, such as the reconstruction of evolutionary history. In this paper, we advance current knowledge, by testing SCJ's ability regarding evolutionary reconstruction in two aspects: 1) How well does SCJ reconstruct evolutionary topologies? and 2) How well does SCJ reconstruct ancestral genomes? In the process of answering these questions, we implemented SCJ-based methods, and made them available to the community. We ran experiments using as many as 200 genomes, with as many as 3,000 genes. For the first question, we found out that SCJ can recover typically between 60 percent and more than 95 percent of the topology, as measured through the Robinson-Foulds distance (a.k.a. split distance) between trees. In other words, 60 percent to more than 95 percent of the original splits are also present in the reconstructed tree. For the second question, given a topology, SCJ's ability to reconstruct ancestral genomes depends on how far from the leaves the ancestral is. For nodes close to the leaves, about 85 percent of the gene adjacencies can be recovered. This percentage decreases as we move up the tree, but, even at the root, about 50 percent of the adjacencies are recovered, for as many as 64 leaves. Our findings corroborate the fact that SCJ leads to very conservative genome reconstructions, yielding very few false-positive gene adjacencies in the ancestrals, at the expense of a relatively larger amount of false negatives. In addition, experiments with real data from the Campanulaceae and Protostomes groups show that SCJ reconstructs topologies of quality comparable to the accepted trees of the species involved. As far as time is concerned, the methods we

  17. Identical TCR beta-chain rearrangements in streptococcal angina and skin lesions of patients with psoriasis vulgaris.

    Science.gov (United States)

    Diluvio, Laura; Vollmer, Sigrid; Besgen, Petra; Ellwart, Joachim W; Chimenti, Sergio; Prinz, Joerg C

    2006-06-01

    Tonsillar infection with Streptococcus pyogenes may induce several nonsuppurative autoimmune sequelae. The precise pathogenetic mechanisms behind this clinically well-established association are still unresolved. Using TCR analysis, we sought to identify a link between streptococcal tonsillitis and the T cell-mediated autoimmune response in psoriasis. Three patients with streptococcal-induced psoriasis underwent tonsillectomy. Using size spectratyping and sequencing of TCR beta-chain variable region gene (TCRBV) rearrangements, we compared the TCR usage of psoriatic skin lesions, blood, tonsils, and tonsillar T cells fractionated according to the expression of the skin address in "cutaneous lymphocyte-associated Ag" (CLA). TCRBV-size spectratype analysis of the blood lymphocytes, tonsils, and the CLA-negative tonsillar T cells revealed largely unselected T cell populations. Instead, TCRBV gene families of the psoriatic lesions and skin-homing CLA-positive tonsillar T cells displayed highly restricted spectratypes. Sequencing of TCRBV cDNA identified various clonal TCRBV rearrangements within the psoriatic lesions that indicated Ag-driven T cell expansion. Several of these clonotypes were also detected within the tonsils and, in one of the patients, within the small subset of CLA-positive tonsillar T cells, suggesting that T cells from the same T cell clones were simultaneously present within skin and tonsillar tissue. Because after tonsillectomy psoriasis cleared in all three patients our observations indicate that T cells may connect psoriatic inflammation to streptococcal angina. They suggest that the chronic streptococcal immune stimulus within the tonsils could act as a source for pathogenic T cells in poststreptococcal disorders, and they may help to explain why eliminating this source with tonsillectomy may improve streptococcal-induced sequelae.

  18. Chromosomal rearrangements directly cause underdominant F1 pollen sterility in Mimulus lewisii-Mimulus cardinalis hybrids.

    Science.gov (United States)

    Stathos, Angela; Fishman, Lila

    2014-11-01

    Chromosomal rearrangements can contribute to the evolution of postzygotic reproductive isolation directly, by disrupting meiosis in F1 hybrids, or indirectly, by suppressing recombination among genic incompatibilities. Because direct effects of rearrangements on fertility imply fitness costs during their spread, understanding the mechanism of F1 hybrid sterility is integral to reconstructing the role(s) of rearrangements in speciation. In hybrids between monkeyflowers Mimulus cardinalis and Mimulus lewisii, rearrangements contain all quantitative trait loci (QTLs) for both premating barriers and pollen sterility, suggesting that they may have facilitated speciation in this model system. We used artificial chromosome doubling and comparative mapping to test whether heterozygous rearrangements directly cause underdominant male sterility in M. lewisii-M. cardinalis hybrids. Consistent with a direct chromosomal basis for hybrid sterility, synthetic tetraploid F1 s showed highly restored fertility (83.4% pollen fertility) relative to diploids F1 s (36.0%). Additional mapping with Mimulus parishii-M. cardinalis and M. parishii-M. lewisii hybrids demonstrated that underdominant male sterility is caused by one M. lewisii specific and one M. cardinalis specific reciprocal translocation, but that inversions had no direct effects on fertility. We discuss the importance of translocations as causes of reproductive isolation, and consider models for how underdominant rearrangements spread and fix despite intrinsic fitness costs.

  19. Mitochondrial tRNA gene translocations in highly eusocial bees

    Directory of Open Access Journals (Sweden)

    Daniela Silvestre

    2006-01-01

    Full Text Available Mitochondrial gene rearrangement events, especially involving tRNA genes, have been described more frequently as more complete mitochondrial genome sequences are becoming available. In the present work, we analyzed mitochondrial tRNA gene rearrangements between two bee species belonging to the tribes Apini and Meliponini within the "corbiculate Apidae". Eleven tRNA genes are in different genome positions or strands. The molecular events responsible for each translocation are explained. Considering the high number of rearrangements observed, the data presented here contradict the general rule of high gene order conservation among closely related organisms, and also represent a powerful molecular tool to help solve questions about phylogeny and evolution in bees.

  20. The complete mitochondrial genome sequence of the spider habronattus oregonensis reveals rearranged and extremely truncated tRNAs

    Energy Technology Data Exchange (ETDEWEB)

    Masta, Susan E.; Boore, Jeffrey L.

    2004-01-31

    We sequenced the entire mitochondrial genome of the jumping spider Habronattus oregonensis of the arachnid order Araneae (Arthropoda: Chelicerata). A number of unusual features distinguish this genome from other chelicerate and arthropod mitochondrial genomes. Most of the transfer RNA gene sequences are greatly reduced in size and cannot be folded into typical cloverleaf-shaped secondary structures. At least nine of the tRNA sequences lack the potential to form TYC arm stem pairings, and instead are inferred to have TV-replacement loops. Furthermore, sequences that could encode the 3' aminoacyl acceptor stems in at least 10 tRNAs appear to be lacking, because fully paired acceptor stems are not possible and because the downstream sequences instead encode adjacent genes. Hence, these appear to be among the smallest known tRNA genes. We postulate that an RNA editing mechanism must exist to restore the 3' aminoacyl acceptor stems in order to allow the tRNAs to function. At least seven tRN As are rearranged with respect to the chelicerate Limulus polyphemus, although the arrangement of the protein-coding genes is identical. Most mitochondrial protein-coding genes of H. oregonensis have ATN as initiation codons, as commonly found in arthropod mtDNAs, but cytochrome oxidase subunit 2 and 3 genes apparently use UUG as an initiation codon. Finally, many of the gene sequences overlap one another and are truncated. This 14,381 bp genome, the first mitochondrial genome of a spider yet sequenced, is one of the smallest arthropod mitochondrial genomes known. We suggest that post transcriptional RNA editing can likely maintain function of the tRNAs while permitting the accumulation of mutations that would otherwise be deleterious. Such mechanisms may have allowed for the minimization of the spider mitochondrial genome.

  1. Programmed genome rearrangements: in lampreys, all cells are not equal.

    Science.gov (United States)

    Sémon, Marie; Schubert, Michael; Laudet, Vincent

    2012-08-21

    How can organisms silence deleterious gene loci? A recent study has shed light on a very brute mechanism in a jawless vertebrate: the irreversible deletion of massive chunks of genomic DNA. PMID:22917513

  2. Recurrent chromosomal rearrangements at bands 8q24 and 11q13 in gastric cancer as detected by multicolor spectral karyotyping

    Institute of Scientific and Technical Information of China (English)

    Yasuhide Yamashita; Akio Hagiwara; Hisakazu Yamagishi; Masafumi Taniwaki; Kazuhiro Nishida; Takashi Okuda; Kenichi Nomura; Yosuke Matsumoto; Shoji Mitsufuji; Shigeo Horiike; Hiroyuki Hata; Chohei Sakakura

    2005-01-01

    AIM: To identify chromosomal translocations specific to gastric cancer (GC), spectral karyotyping (SKY) analysis was performed on established cell lines and cancerous ascitic fluids.METHODS: SKY analysis of 10 established cell lines and seven cancerous ascitic fluid samples identified recurrent chromosomal breakpoints and translocations in GC,several of which involved chromosomal loci of oncogenes or tumor suppressor genes.RESULTS: A total of 630 chromosomal breaks were identified. Chromosome no.8 was the most frequently involved in rearrangements (65 breaks), followed by chromosomes no. 11 (53), no. 1 (49), no. 7 (46), no. 13 (37), no. 3 (36), no. 17 (33), and no. 20 (29). Frequent breakpoints were detected in 8q24.1 (30 breaks), 11q13 (29), 13q14 (16), 20q11.2 (14), 7q32 (13), 17q11.2 (13),18q21 (12), 17q23 (9), 18q11.2 (9). SKY analysis identified a total of 242 chromosomal rearrangements including 190 reciprocal and non-reciprocal translocations. The recurrent combinations of chromosomal bands involved in translocations were 8q24.1 and 13q14 (3 cases), 8q24.1 and 11q13 (3), 11q13 and 17q11.2 (2), and 18q11.2 and 20q11.2 (2). Our study validated the ability of SKY to characterize in detail the chromosomal rearrangements in solid tumors and derived cell lines. Moreover,fluorescence in situ hybridization helped to identify the insertions, translocations, and homogeneously staining regions of MYCand CCND1 gene loci.CONCLUSION: The non-random co-localization of certain cytogenetic bands suggests the importance of chromosomal translocations in gastric carcinogenesis, by serving as landmarks for the cloning of GC causing genes.

  3. The complete chloroplast genome sequence of Pelargonium x hortorum: organization and evolution of the largest and most highly rearranged chloroplast genome of land plants.

    Science.gov (United States)

    Chumley, Timothy W; Palmer, Jeffrey D; Mower, Jeffrey P; Fourcade, H Matthew; Calie, Patrick J; Boore, Jeffrey L; Jansen, Robert K

    2006-11-01

    The chloroplast genome of Pelargonium x hortorum has been completely sequenced. It maps as a circular molecule of 217,942 bp and is both the largest and most rearranged land plant chloroplast genome yet sequenced. It features 2 copies of a greatly expanded inverted repeat (IR) of 75,741 bp each and, consequently, diminished single-copy regions of 59,710 and 6,750 bp. Despite the increase in size and complexity of the genome, the gene content is similar to that of other angiosperms, with the exceptions of a large number of pseudogenes, the recognition of 2 open reading frames (ORF56 and ORF42) in the trnA intron with similarities to previously identified mitochondrial products (ACRS and pvs-trnA), the losses of accD and trnT-ggu and, in particular, the presence of a highly divergent set of rpoA-like ORFs rather than a single, easily recognized gene for rpoA. The 3-fold expansion of the IR (relative to most angiosperms) accounts for most of the size increase of the genome, but an additional 10% of the size increase is related to the large number of repeats found. The Pelargonium genome contains 35 times as many 31 bp or larger repeats than the unrearranged genome of Spinacia. Most of these repeats occur near the rearrangement hotspots, and 2 different associations of repeats are localized in these regions. These associations are characterized by full or partial duplications of several genes, most of which appear to be nonfunctional copies or pseudogenes. These duplications may also be linked to the disruption of at least 1 but possibly 2 or 3 operons. We propose simple models that account for the major rearrangements with a minimum of 8 IR boundary changes and 12 inversions in addition to several insertions of duplicated sequence.

  4. Identification of leukemia-associated genes by MLL-EEN fusion protein through dysregulation of histone modification and DNA methylation

    OpenAIRE

    Lui, Wing-chi; 呂穎芝

    2012-01-01

    Mixed lineage leukemia (MLL) gene undergoes chromosomal translocation with over 60 different fusion partner genes in human leukemias. The resultant MLL-fusion oncoproteins are profoundly implicated in leukemias with poor prognosis. Epigenetic dysregulations have been frequently reported in MLL-rearranged leukemogenesis. Our study aims to investigate the correlations between epigenetic alterations, including both histone modification and DNA methylation, and gene dysregulation in MLL-rearrange...

  5. Variable Lipoprotein Genes of Mycoplasma agalactiae Are Activated In Vivo by Promoter Addition via Site-Specific DNA Inversions

    OpenAIRE

    Flitman-Tene, Ravenna; Mudahi-Orenstein, Sigalit; Levisohn, Sharon; Yogev, David

    2003-01-01

    Mycoplasma agalactiae, the etiological agent of contagious agalactia of small ruminants, has a family of related genes (avg genes) which encode surface lipoprotein antigens that undergo phase variation. A series of 13 M. agalactiae clonal isolates, obtained from one chronically infected animal over a period of 7 months, were found to undergo major rearrangement events within the avg genomic locus. We show that these rearrangements regulate the phase-variable expression of individual avg genes...

  6. Mycoreovirus genome alterations: similarities to and differences from rearrangements reported for other reoviruses

    Directory of Open Access Journals (Sweden)

    Toru eTanaka

    2012-06-01

    Full Text Available The family Reoviridae is one of the largest virus families with genomes composed of 9 to 12 double-stranded RNA segments. It includes members infecting organisms from protists to humans. It is well known that reovirus genomes are prone to various types of genome alterations including intragenic rearrangement and reassortment under laboratory and natural conditions. Recently distinct genetic alterations were reported for members of the genus Mycoreovirus, Mycoreovirus 1 (MyRV1 and MyRV3 with 11 (S1–S11 and 12 genome segments (S1–S12, respectively. While MyRV3 S8 is lost during subculturing of infected host fungal strains, MyRV1 rearrangements undergo alterations spontaneously and inducibly. The inducible MyRV1 rerarrangements are different from any other previous examples of reovirus rearrangements in their dependence on an unrelated virus factor, a multifunctional protein, p29, encoded by a distinct virus Cryphonectria parasitica hypovirus 1 (CHV1. A total of 5 MyRV1 variants with genome rearranged segments (S1-S3, S6 and S10 are generated in the background of a single viral strain in the presence of CHV1 p29 supplied either transgenically or by coinfection. MyRV1 S4 and S10 are rearranged, albeit very infrequently, in a CHV1-p29 independent fashion. A variant of MyRV1 with substantial deletions in both S4 and S10, generated through a combined reassortment and rearrangement approach, shows comparable replication levels to the wild-type MyRV1. In vivo and in vitro interactions of CHV1 p29 and MyRV1 VP9 are implicated in the induction of MyRV1 rearrangements. However, the mechanism underlying p29-mediated rearrangements remains largely unknown. MyRV1 S4 rearrangements spontaneously occurred independently of CHV1 p29. In the absence of reverse genetics systems for mycoreoviruses, molecular and biological characterization of these MyRV1 and MyRV3 variants contribute to functional analyses of the protein products encoded by those rearranged

  7. De novo complex intra chromosomal rearrangement after ICSI: characterisation by BACs micro array-CGH

    Directory of Open Access Journals (Sweden)

    Quimsiyeh Mazin

    2008-12-01

    Full Text Available Abstract Background In routine Assisted Reproductive Technology (ART men with severe oligozoospermia or azoospermia should be informed about the risk of de novo congenital or chromosomal abnormalities in ICSI program. Also the benefits of preimplantation or prenatal genetic diagnosis practice need to be explained to the couple. Methods From a routine ICSI attempt, using ejaculated sperm from male with severe oligozoospermia and having normal karyotype, a 30 years old pregnant woman was referred to prenatal diagnosis in the 17th week for bichorionic biamniotic twin gestation. Amniocentesis was performed because of the detection of an increased foetal nuchal translucency for one of the fetus by the sonographic examination during the 12th week of gestation (WG. Chromosome and DNA studies of the fetus were realized on cultured amniocytes Results Conventional, molecular cytogenetic and microarray CGH experiments allowed us to conclude that the fetus had a de novo pericentromeric inversion associated with a duplication of the 9p22.1-p24 chromosomal region, 46,XY,invdup(9(p22.1p24 [arrCGH 9p22.1p24 (RP11-130C19 → RP11-87O1x3]. As containing the critical 9p22 region, our case is in coincidence with the general phenotype features of the partial trisomy 9p syndrome with major growth retardation, microcephaly and microretrognathia. Conclusion This de novo complex chromosome rearrangement illustrates the possible risk of chromosome or gene defects in ICSI program and the contribution of array-CGH for mapping rapidly de novo chromosomal imbalance.

  8. De novo complex intra chromosomal rearrangement after ICSI: characterisation by BACs micro array-CGH

    Science.gov (United States)

    Kasakyan, Serdar; Lohmann, Laurence; Aboura, Azeddine; Quimsiyeh, Mazin; Menezo, Yves; Tachdjian, Gerard; Benkhalifa, Moncef

    2008-01-01

    Background In routine Assisted Reproductive Technology (ART) men with severe oligozoospermia or azoospermia should be informed about the risk of de novo congenital or chromosomal abnormalities in ICSI program. Also the benefits of preimplantation or prenatal genetic diagnosis practice need to be explained to the couple. Methods From a routine ICSI attempt, using ejaculated sperm from male with severe oligozoospermia and having normal karyotype, a 30 years old pregnant woman was referred to prenatal diagnosis in the 17th week for bichorionic biamniotic twin gestation. Amniocentesis was performed because of the detection of an increased foetal nuchal translucency for one of the fetus by the sonographic examination during the 12th week of gestation (WG). Chromosome and DNA studies of the fetus were realized on cultured amniocytes Results Conventional, molecular cytogenetic and microarray CGH experiments allowed us to conclude that the fetus had a de novo pericentromeric inversion associated with a duplication of the 9p22.1-p24 chromosomal region, 46,XY,invdup(9)(p22.1p24) [arrCGH 9p22.1p24 (RP11-130C19 → RP11-87O1)x3]. As containing the critical 9p22 region, our case is in coincidence with the general phenotype features of the partial trisomy 9p syndrome with major growth retardation, microcephaly and microretrognathia. Conclusion This de novo complex chromosome rearrangement illustrates the possible risk of chromosome or gene defects in ICSI program and the contribution of array-CGH for mapping rapidly de novo chromosomal imbalance. PMID:19105807

  9. 32P-incorporation PCR for the detection of rearrangements at the TCR-gamma locus.

    Science.gov (United States)

    Short, M A; Evans, P A; Shiach, C R; Jack, A; Richards, S; Morgan, G J

    1996-03-01

    We have adapted and developed a PCR (polymerase chain reaction)-based technique for the T-cell receptor (TCR)-gamma chain gene, which has subsequently been used for routine diagnosis. Variable-region oligonucleotide primers were chosen from subgroups I and II, and the joining region primer was from the J2 segment. The primers were used to perform a 32P-incorporation PCR, and the products were then separated on an 8% denaturing polyacrylamide gel. In our hands, this technique is more reliable than cold methods, when separation is performed on either agarose or nondenaturing polyacrylamide. The radioactive technique was used to look at 102 T-cell proliferations, of which eight of eight T-acute lymphoblastic leukemia (ALL), 24 of 34 T-non-Hodgkin's leukemia (NHL), and 35 of 60 large granular lymphocyte (LGL) expansions were clonal. Of 122 B-cell proliferations investigated, including 72 cases of B-cell lineage ALL, 36 demonstrated a T-cell rearrangement (33 ALLs and three myelomas). Samples from nonlymphoid tumors were tested and produced a normal distribution ladder of PCR products after autoradiography, a pattern also observed with antenatal and preoperative patients. The radiolabel-incorporation method detected an abnormal pattern of a ladder with prominent dark bands in 29 of 122 B-cell and 27 of 102 T-cell cases and in 0 of 49 of the nonlymphoid and normal samples. The abnormal banding patterns obtained in a proportion of the B- and T-cell cases was not readily discernible by nondenaturing-acrylamide or agarose-separation methods.

  10. Consistency of VDJ Rearrangement and Substitution Parameters Enables Accurate B Cell Receptor Sequence Annotation.

    Directory of Open Access Journals (Sweden)

    Duncan K Ralph

    2016-01-01

    Full Text Available VDJ rearrangement and somatic hypermutation work together to produce antibody-coding B cell receptor (BCR sequences for a remarkable diversity of antigens. It is now possible to sequence these BCRs in high throughput; analysis of these sequences is bringing new insight into how antibodies develop, in particular for broadly-neutralizing antibodies against HIV and influenza. A fundamental step in such sequence analysis is to annotate each base as coming from a specific one of the V, D, or J genes, or from an N-addition (a.k.a. non-templated insertion. Previous work has used simple parametric distributions to model transitions from state to state in a hidden Markov model (HMM of VDJ recombination, and assumed that mutations occur via the same process across sites. However, codon frame and other effects have been observed to violate these parametric assumptions for such coding sequences, suggesting that a non-parametric approach to modeling the recombination process could be useful. In our paper, we find that indeed large modern data sets suggest a model using parameter-rich per-allele categorical distributions for HMM transition probabilities and per-allele-per-position mutation probabilities, and that using such a model for inference leads to significantly improved results. We present an accurate and efficient BCR sequence annotation software package using a novel HMM "factorization" strategy. This package, called partis (https://github.com/psathyrella/partis/, is built on a new general-purpose HMM compiler that can perform efficient inference given a simple text description of an HMM.

  11. Detection and precise mapping of germline rearrangements in BRCA1, BRCA2, MSH2, and MLH1 using zoom-in array comparative genomic hybridization (aCGH)

    DEFF Research Database (Denmark)

    Staaf, Johan; Törngren, Therese; Rambech, Eva;

    2008-01-01

    of primers for sequence determination of the breakpoints. The array platform can be streamlined for a particular application, e.g., focusing on breast cancer susceptibility genes, with increased capacity using multiformat design, and represents a valuable new tool and complement for genetic screening......Disease-predisposing germline mutations in cancer susceptibility genes may consist of large genomic rearrangements that are challenging to detect and characterize using standard PCR-based mutation screening methods. Here, we describe a custom-made zoom-in microarray comparative genomic...... hybridization (CGH) platform of 60mer oligonucleotides. The 4 x 44 K array format provides high-resolution coverage (200-300 bp) of 400-700 kb genomic regions surrounding six cancer susceptibility genes. We evaluate its performance to accurately detect and precisely map earlier described or novel large germline...

  12. No evidence for the use of DIR, D-D fusions, chromosome 15 open reading frames or VH replacement in the peripheral repertoire was found on application of an improved algorithm, JointML, to 6329 human immunoglobulin H rearrangements

    DEFF Research Database (Denmark)

    Ohm-Laursen, Line; Nielsen, Morten; Larsen, Stine R;

    2006-01-01

    Antibody diversity is created by imprecise joining of the variability (V), diversity (D) and joining (J) gene segments of the heavy and light chain loci. Analysis of rearrangements is complicated by somatic hypermutations and uncertainty concerning the sources of gene segments and the precise way...... gene (VH) replacement. Safe conclusions require large, well-defined sequence samples and algorithms minimizing stochastic assignment of segments. Two computer programs were developed for analysis of heavy chain joints. JointHMM is a profile hidden Markow model, while JointML is a maximum...

  13. Dysregulation of the DNA Damage Response and KMT2A Rearrangement in Fetal Liver Hematopoietic Cells.

    Directory of Open Access Journals (Sweden)

    Mai Nanya

    Full Text Available Etoposide, a topoisomerase 2 (TOP2 inhibitor, is associated with the development of KMT2A (MLL-rearranged infant leukemia. An epidemiological study suggested that in utero exposure to TOP2 inhibitors may be involved in generation of KMT2A (MLL rearrangement. The present study examined the mechanism underlying the development of KMT2A (MLL-rearranged infant leukemia in response to in utero exposure to etoposide in a mouse model. Fetal liver hematopoietic stem cells were more susceptible to etoposide than maternal bone marrow mononuclear cells. Etoposide-induced Kmt2a breakage was detected in fetal liver hematopoietic stem cells using a newly developed chromatin immunoprecipitation (ChIP assay. Assessment of etoposide-induced chromosomal translocation by next-generation RNA sequencing (RNA-seq identified several chimeric fusion messenger RNAs that were generated by etoposide treatment. However, Kmt2a (Mll-rearranged fusion mRNA was detected in Atm-knockout mice, which are defective in the DNA damage response, but not in wild-type mice. The present findings suggest that in utero exposure to TOP2 inhibitors induces Kmt2a rearrangement when the DNA damage response is defective.

  14. Alu elements mediate large SPG11 gene rearrangements: further spatacsin mutations.

    NARCIS (Netherlands)

    Conceicao Pereira, M.; Loureiro, J.L.; Pinto-Basto, J.; Brandao, E.; Margarida Lopes, A.; Neves, G.; Dias, P.; Geraldes, R.; Martins, I.P.; Cruz, V.T.; Kamsteeg, E.J.; Brunner, H.G.; Coutinho, P.; Sequeiros, J.; Alonso, I.

    2012-01-01

    PURPOSE: Hereditary spastic paraplegias compose a group of neurodegenerative disorders with a large clinical and genetic heterogeneity. Among the autosomal recessive forms, spastic paraplegia type 11 is the most common. METHODS: To better understand the spastic paraplegia type 11 mutation spectrum,

  15. Rearrangement of nucleosome structure during excision repair in xeroderma pigmentosum (group A) human fibroblasts

    International Nuclear Information System (INIS)

    Rearrangements of chromatic structure during excision repair were examined in xeroderma pigmentosum (XP; complementation group A) human fibroblasts treated with the small-molecule alkylating agent methyl methanesulfonate (MMS). We observed normal levels of repair synthesis in these cells during the first 12 h after exposure to MMS, in contrast to the near zero incorporation of repair patches following exposure to u.v. light. Our results indicate that the relative nuclease sensitivity of newly repaired regions in MMS-treated XP (group A) cells is quantitatively similar to that of newly repaired regions in MMS-treated normal human fibroblasts. This enhanced sensitivity is accompanied by a marked under-representation of repair-incorporated nucleotides in isolated nucleosome core DNA. Pulse-chase experiments demonstrated that these regions rapidly undergo rearrangements in chromatin structure, and both the rate and extent of these rearrangements are similar to those observed in normal cells. (author)

  16. Comments on the Invariance of Physical Laws Under Particle Re-Arrangement

    CERN Document Server

    Spaans, M

    2007-01-01

    Observationally and experimentally, physical laws express how particles interact. Conversely, physical laws should be invariant under any re-arrangement of those particles, e.g., the laws of gravity do not change if one re-arranges the stars in the sky. To explore the physical meaning of these assertions, arguments are presented that show how the freedom of particle re-arrangement leads to an identical twin associated with any photon. These twins can become spatially separated for astronomically distant objects and are special in that detection of the one causes the disapperance of the other. A tilting detector then leads to brightness variations across an image for twin separations on the order of the detector size.

  17. Strong fields induce ultrafast rearrangement of H-atoms in H$_2$O

    CERN Document Server

    Rajgara, F A; Dharmadhikari, A K; Safvan, C P

    2008-01-01

    H-atoms in H$_2$O are rearranged by strong optical fields generated by intense, 10 fs laser pulses to form H$_2^+$, against prevailing wisdom that strong fields inevitably lead to multiple molecular ionization and the subsequent Coulomb explosion into fragments. This atomic rearrangement is shown to occur within a single 10 fs pulse. Comparison with results obtained with $\\sim$300-attosecond long strong fields generated using fast Si$^{8+}$ ions helps establish thresholds for field strength and time required for such rearrangements. Quantum-chemical calculations reveal that H$_2^+$ originates in the $^1$A state of H$_2$O$^{2+}$ when the O-H bond elongates to 1.15 a.u. and the H-O-H angle becomes 120$^o$. Bond formation on the ultrafast timescale of molecular vibrations (10 fs for H$_2^+$) has hitherto not been reported.

  18. Estimation of kinetics parameters in Beckmann rearrangement of cyclohexanone oxime using genetic algorithm

    Institute of Scientific and Technical Information of China (English)

    WU Jian; LI Zhong; LUO He-an

    2006-01-01

    Beckmann rearrangement mechanism of cyclohexanone oxime, based on the characteristic of self-catalyzed reaction and polymorphism was proposed. According to the suggested mechanism, the basic approach was the rearrangement of OXH+ while the SO3 acts as dehydrating agent and OXSO3 can turn to CPLSO3 ultimately. Considering self-catalyzed reaction between OXSO3 and CPLH+ , kinetic model for Beckmann rearrangement was established. Corresponding parameters were estimated by using float genetic algorithm (GA) and simulation results agree well with the experimental data below -19.3℃. Industrial equipment was simulated and analyzed. Effects of key process parameters such as molar ratio of sulfuric acid to oxime and circulation ratio on the residual oxime are also discussed. The results show that the caprolactam exists as CPLH+ finally in oleum and the minimum molecular ratio of sulfuric acid to oxime can be 0.5 theoretically.

  19. The clinical significance of 8q24/MYC rearrangement in chronic lymphocytic leukemia.

    Science.gov (United States)

    Li, Yan; Hu, Shimin; Wang, Sa A; Li, Shaoying; Huh, Yang O; Tang, Zhenya; Medeiros, L Jeffrey; Tang, Guilin

    2016-05-01

    Chromosome 8q24/MYC rearrangement is associated with Burkitt lymphoma and some aggressive B-cell lymphomas, but is rare in chronic lymphocytic leukemia. We here report a cohort of 20 chronic lymphocytic leukemia patients with 8q24/MYC rearrangement, 3 detected at time of initial diagnosis and 17 acquired after a median interval of 48 months. At the time when 8q24/MYC arrangement was detected, 18 patients had B-symptoms, 17 had lymphadenopathy, and 17 had splenomegaly. Histologically, typical chronic lymphocytic leukemia morphology was seen in six patients, increased prolymphocytes in nine and Richter's transformation in five patients. Eighteen patients had karyotypic information available that showed t(8;v) in a complex karyotype in 12 patients and in a non-complex karyotype in 6 patients. Fluorescence in situ hybridization confirmed MYC rearrangement in 17/17 patients. All patients required therapy after 8q24/MYC rearrangement was detected. At last follow-up, five of six patients with a non-complex karyotype were alive after a median of 74 months (10~143 months) from the detection of 8q24/MYC rearrangement. In contrast, 10 of 12 patients with a complex karyotype died with a median survival of 5.5 months. We conclude that 8q24/MYC rearrangement in chronic lymphocytic leukemia is rare and often acquired during the course of disease. If it is presented in a complex karyotype, it is often associated with Richter's transformation, refractory to therapy and an aggressive clinical course; on the other hand, if it is present in a non-complex karyotype, patients often respond to risk-adapted therapies and achieve remission. PMID:26916070

  20. Comparison of somatic mutation frequency among immunoglobulin genes.

    Science.gov (United States)

    Motoyama, N; Miwa, T; Suzuki, Y; Okada, H; Azuma, T

    1994-02-01

    We analyzed the frequency of somatic mutation in immunoglobulin genes from hybridomas that secrete anti-(4-hydroxy-3-nitrophenyl)acetyl (NP) monoclonal antibodies. A high frequency of mutation (3.3-4.4%) was observed in both the rearranged VH186.2 and V lambda 1 genes, indicating that somatic mutation occurs with similar frequency in these genes in spite of the absence of an intron enhancer in lambda 1 chain genes. In contrast to the high frequency in J-C introns, only two nucleotide substitutions occurred at positions -462 and -555 in the 5' noncoding region in one of the lambda 1-chain genes and in none of the other three so far studied. Since a similar low frequency of somatic mutation was observed in the 5' noncoding region of inactive lambda 2-chain genes rendered inactive because of incorrect rearrangement, this region may not be a target or alternatively, may be protected from the mutator system. We observed a low frequency of nucleotide substitution in unrearranged V lambda 1 genes (approximately 1/15 that of rearranged genes). Together with previous results (Azuma T., N. Motoyama, L. Fields, and D. Loh, 1993. Int. Immunol. 5:121), these findings suggest that the 5' noncoding region, which contains the promoter element, provides a signal for the somatic mutator system and that rearrangement, which brings the promoter into close proximity to the enhancer element, should increase mutation efficiency.

  1. Application of exterior complex scaling to positron-hydrogencollisions including rearrangement

    Energy Technology Data Exchange (ETDEWEB)

    Bartlett, Philip L.; Stelbovics, Andris T.; Rescigno, Thomas N.; McCurdy, C. William

    2007-12-06

    The first application of an exterior complex scaling method to an atomic scattering problem with distinct rearrangement channels is reported. Calculations are performed for positron-hydrogen collisions in an s-wave model employing an electron-positron potential of V{sub 12} = -(8+(r{sub 1}-r{sub 2}){sup 2}){sup 1/2}, using the time-independent propagating exterior complex scaling (PECS) method. This potential has the correct long-range Coulomb tail of the full problem and the results demonstrate that ECS-based methods can accurately calculate scattering, ionization and positronium formation cross sections in this three-body rearrangement collision.

  2. Theory of VVER-1000 fuel rearrangement optimization taking into account both fuel cladding durability and burnup

    International Nuclear Information System (INIS)

    Using the VVER-1000 fuel element (FE) cladding failure estimation method based on creep energy theory (CET-method), it is shown that practically FE cladding rupture life at normal operation conditions can be controlled by an optimal assignment of fuel assembly (FA) rearrangement algorithm. The probabilistic FA rearrangement efficiency criterion based on Monte Carlo Sampling takes into account robust operation conditions and gives results corresponding to the deterministic ones in principle, though the robust efficiency estimation is more conservative. It is proved that CET-method allows us to create an automated complex controlling FE cladding durability in VVER-1000.

  3. Rearrangement of the breakpoint cluster region in Philadelphia chromosome positive acute leukemia.

    OpenAIRE

    Takahashi, Isao; Sekito,Noriko; Takeuchi, Makoto; Osada, Ken; Matsuzaki,Toshiro; Fukuda, Shunichi; Lai,Minyu; Uchida, Kozaburo; Kimura,Ikuro; Miyamoto,Kanji; Kitajima,Koichi; Sanada, Hiroshi

    1988-01-01

    The rearrangement of breakpoint cluster region (ber) was examined in leukemic cells obtained from 3 patients initially diagnosed as having Ph+ acute leukemia, 2 with acute lymphocytic leukemia (ALL) and one with acute mixed leukemia. DNA was digested with Bgl II and BamH I. The ber rearrangement was present in the case of acute mixed leukemia (Case 1), but was absent in the 2 cases of ALL (Cases 2 and 3). These results suggest that Case 1 represented a type of blast crisis of chronic myelocyt...

  4. Unexpected rearrangements in the synthesis of an unsymmetrical tridentate dianionic N-heterocyclic carbene

    KAUST Repository

    Despagnet-Ayoub, Emmanuelle

    2013-01-01

    Starting from the same ethylenediamine species, three valuable carbene precursors were synthesized under differing conditions: a tridentate dianionic N-heterocyclic carbene bearing an aniline, a phenol and a central dihydroimidazolium salt, its benzimidazolium isomer by intramolecular rearrangement and a dicationic benzimidazolium-benzoxazolium salt by changing the Brønsted acid from HCl to HBF4. A DFT study was performed to understand the rearrangement pathway. The structure of a bis[(NCO)carbene] zirconium complex was determined. © 2013 The Royal Society of Chemistry.

  5. Aminocyclopentanols as sugar mimics. Synthesis from unsaturated bicyclic lactones by Overman rearrangement

    DEFF Research Database (Denmark)

    Bøjstrup, Marie; Fanefjord, Mette; Lundt, Inge

    2007-01-01

    Bicyclic cyclopentane lactones, prepared from bromodeoxyaldonolactones, were transformed into aminocyclopentanols with an Overman rearrangement as the key step. Two of the compounds prepared, 7 and 19, were found to be good inhibitors of jack bean alpha-mannosidase and beta-D-N-acetylglucosaminid......Bicyclic cyclopentane lactones, prepared from bromodeoxyaldonolactones, were transformed into aminocyclopentanols with an Overman rearrangement as the key step. Two of the compounds prepared, 7 and 19, were found to be good inhibitors of jack bean alpha-mannosidase and beta...

  6. Novel Rearrangement of Small Peptides in Electrospray Ionization Tandem Mass Spectrometry

    Institute of Scientific and Technical Information of China (English)

    CHEN,Yi(陈益); WANG,Jin(王津); LIU,Xiao-Hong(刘晓红); SUN,Ming(孙命); CHEN,Jing(陈晶); JIANG,Yang(江洋); ZHAO,Yu-Fen(赵玉芬)

    2004-01-01

    Electrospray ionization mass spectrometry (ESI-MS) is a powerful method for sequencing peptides.A novel fragmentation pattern with the loss of a neutral fragment of 45 Da was observed with the dipeptides,tripeptides,tetrapeptides and pentapeptides containing phenylalanine or histidine residues.A novel rearrangement reaction with the extrusion of a formamide piece was studied and the rearrangement mechanism was proposed and confirmed by deuterium labeling experiments with ESI-MSn and high-resolution mass spectrometry.These findings are potentially helpful in identifying the specific sequence pattern in the peptide sequencing.

  7. DGGE based whole-gene mutation scanning of the dystrophlin gene in Duchenne and Becker muscular dystrophy patients

    NARCIS (Netherlands)

    Hofstra, RMW; Mulder, IM; Vossen, R; de Koning-Gans, PAM; Kraak, M; Ginjaar, IB; van der Hout, AH; Bakker, E; Buys, CHCM; van Essen, AJ; den Dunnen, JT

    2004-01-01

    Duchenne and Becker muscular dystrophy (DMD and BMD) are caused by mutations in the dystrophin gene. Large rearrangements in the gene are found in about two,thirds of DMD patients, with similar to60% carrying deletions and 5-10% carrying duplications. Most of the remaining 30-35% of patients are exp

  8. Mapping autism risk loci using genetic linkage and chromosomal rearrangements

    Science.gov (United States)

    Szatmari, Peter; Paterson, Andrew; Zwaigenbaum, Lonnie; Roberts, Wendy; Brian, Jessica; Liu, Xiao-Qing; Vincent, John; Skaug, Jennifer; Thompson, Ann; Senman, Lili; Feuk, Lars; Qian, Cheng; Bryson, Susan; Jones, Marshall; Marshall, Christian; Scherer, Stephen; Vieland, Veronica; Bartlett, Christopher; Mangin, La Vonne; Goedken, Rhinda; Segre, Alberto; Pericak-Vance, Margaret; Cuccaro, Michael; Gilbert, John; Wright, Harry; Abramson, Ruth; Betancur, Catalina; Bourgeron, Thomas; Gillberg, Christopher; Leboyer, Marion; Buxbaum, Joseph; Davis, Kenneth; Hollander, Eric; Silverman, Jeremy; Hallmayer, Joachim; Lotspeich, Linda; Sutcliffe, James; Haines, Jonathan; Folstein, Susan; Piven, Joseph; Wassink, Thomas; Sheffield, Val; Geschwind, Daniel; Bucan, Maja; Brown, Ted; Cantor, Rita; Constantino, John; Gilliam, Conrad; Herbert, Martha; Lajonchere, Clara; Ledbetter, David; Lese-Martin, Christa; Miller, Janet; Nelson, Stan; Samango-Sprouse, Carol; Spence, Sarah; State, Matthew; Tanzi, Rudolph; Coon, Hilary; Dawson, Geraldine; Devlin, Bernie; Estes, Annette; Flodman, Pamela; Klei, Lambertus; Mcmahon, William; Minshew, Nancy; Munson, Jeff; Korvatska, Elena; Rodier, Patricia; Schellenberg, Gerard; Smith, Moyra; Spence, Anne; Stodgell, Chris; Tepper, Ping Guo; Wijsman, Ellen; Yu, Chang-En; Rogé, Bernadette; Mantoulan, Carine; Wittemeyer, Kerstin; Poustka, Annemarie; Felder, Bärbel; Klauck, Sabine; Schuster, Claudia; Poustka, Fritz; Bölte, Sven; Feineis-Matthews, Sabine; Herbrecht, Evelyn; Schmötzer, Gabi; Tsiantis, John; Papanikolaou, Katerina; Maestrini, Elena; Bacchelli, Elena; Blasi, Francesca; Carone, Simona; Toma, Claudio; Van Engeland, Herman; De Jonge, Maretha; Kemner, Chantal; Koop, Frederieke; Langemeijer, Marjolein; Hijmans, Channa; Staal, Wouter; Baird, Gillian; Bolton, Patrick; Rutter, Michael; Weisblatt, Emma; Green, Jonathan; Aldred, Catherine; Wilkinson, Julie-Anne; Pickles, Andrew; Le Couteur, Ann; Berney, Tom; Mcconachie, Helen; Bailey, Anthony; Francis, Kostas; Honeyman, Gemma; Hutchinson, Aislinn; Parr, Jeremy; Wallace, Simon; Monaco, Anthony; Barnby, Gabrielle; Kobayashi, Kazuhiro; Lamb, Janine; Sousa, Ines; Sykes, Nuala; Cook, Edwin; Guter, Stephen; Leventhal, Bennett; Salt, Jeff; Lord, Catherine; Corsello, Christina; Hus, Vanessa; Weeks, Daniel; Volkmar, Fred; Tauber, Maïté; Fombonne, Eric; Shih, Andy; Meyer, Kacie

    2007-01-01

    Autism spectrum disorders (ASD) are common, heritable neurodevelopmental conditions. The genetic architecture of ASD is complex, requiring large samples to overcome heterogeneity. Here we broaden coverage and sample size relative to other studies of ASD by using Affymetrix 10K single nucleotide polymorphism (SNP) arrays and 1168 families with ≥ 2 affected individuals to perform the largest linkage scan to date, while also analyzing copy number variation (CNV) in these families. Linkage and CNV analyses implicate chromosome 11p12-p13 and neurexins, respectively, amongst other candidate loci. Neurexins team with previously-implicated neuroligins for glutamatergic synaptogenesis, highlighting glutamate-related genes as promising candidates for ASD. PMID:17322880

  9. Preliminary Report of Molecular Detection of Retinoblastoma Gene Mutations

    Institute of Scientific and Technical Information of China (English)

    1994-01-01

    To develop gene diagnosis for retinoblastoma predisposition, it is necessary to disclose the retinoblastoma gene mutations or deletions in detail. Genomic DNA from tumor and peripheral white blood cells in 33 patients with retinoblastoma was detected with 3.8kb probe derived from 3' end of retinoblastoma gene cDNA. The gene abnormalities, including deletion, partial deletion and rearrangement, were found in 18 patients. Further research will be aimed at microdeletions or mutations for those patients wti...

  10. Large BRCA1 and BRCA2 genomic rearrangements in Danish high risk breast-ovarian cancer families

    DEFF Research Database (Denmark)

    Hansen, Thomas v O; Jønson, Lars; Albrechtsen, Anders;

    2009-01-01

    BRCA1 and BRCA2 germ-line mutations predispose to breast and ovarian cancer. Large genomic rearrangements of BRCA1 account for 0-36% of all disease causing mutations in various populations, while large genomic rearrangements in BRCA2 are more rare. We examined 642 East Danish breast and/or ovarian...

  11. Detection of novel and potentially actionable anaplastic lymphoma kinase (ALK) rearrangement in colorectal adenocarcinoma by immunohistochemistry screening

    OpenAIRE

    Lee, Jeeyun; Kim, Hee Cheol; Hong, Jung Yong; Wang, Kai; Kim, Sun Young; Jang, Jiryeon; Kim, Seung Tae; Park, Joon Oh; Lim, Ho Yeong; Kang, Won Ki; Park, Young Suk; Lee, Jiyun; Lee, Woo Yong; Park, Yoon Ah; Huh, Jung Wook

    2015-01-01

    Purpose Anaplastic lymphoma kinase (ALK) rearrangement has been detected in colorectal carcinoma (CRC) using advanced molecular diagnostics tests including exon scanning, fluorescence in situ hybridization (FISH), and next generation sequencing (NGS). We investigated if immunohistochemistry (IHC) can be used to detect ALK rearrangement in gastrointestinal malignancies. Experimental designs Tissue microarrays (TMAs) from consecutive gastric carcinoma (GC) and CRC patients who underwent surgica...

  12. Submicrosecond rearrangeable nonblocking silicon-on-insulator thermo-optic 4x4 switch matrix.

    Science.gov (United States)

    Li, Yuntao; Yu, Jinzhong; Chen, Shaowu; Li, Yanping; Chen, Yuanyuan

    2007-03-15

    A rearrangeable nonblocking silicon-on-insulator-based thermo-optic 4x4 switch matrix is designed and fabricated. A spot-size converter is integrated to reduce the insertion loss, and a new driving circuit is designed to improve the response speed. The insertion loss is less than 10 dB, and the response time is 950 ns. PMID:17308574

  13. Effects of structural rearrangements on the rheology of rennet-induced casein particle gels

    NARCIS (Netherlands)

    Mellema, M.; Walstra, P.; Opheusden, van J.H.J.; Vliet, van T.

    2002-01-01

    During ageing of casein or skim milk gels, structural changes take place that affect gel parameters, such as pore size and storage modulus. These changes can be explained in terms of rearrangements of the gel network at various length scales. In this paper, rheological experiments on rennet-induced

  14. Reactions of unsaturated compounds. CXXIV. Claisen rearrangement of allyl and propargyloxydienyl phosphonates

    Energy Technology Data Exchange (ETDEWEB)

    Dangyan, Yu.M.; Tirakyan, M.R.; Panosyan, G.A.; Badanyan, Sh.O.

    1986-12-20

    O,O-Dialkyl-1-ethylidene-2-allyl(propargyl)oxy-2-butenyl phosphonates have been obtained from vinylallenyl phosphonates and undergo thermal Claisen rearrangement to form highly unsaturated ketophosphonates. Comprehensive coupling constant and chemical shift figures from an NMR analysis are given.

  15. Replication stalling by catalytically impaired Twinkle induces mitochondrial DNA rearrangements in cultured cells

    NARCIS (Netherlands)

    Pohjoismaki, J.L.; Goffart, S.; Spelbrink, J.N.

    2011-01-01

    Pathological mitochondrial DNA (mtDNA) rearrangements have been proposed to result from repair of double-strand breaks caused by blockage of mitochondrial DNA (mtDNA) replication. As mtDNA deletions are seen only in post-mitotic tissues, it has been suggested that they are selected out in actively d

  16. The landscape of somatic mutations in infant MLL-rearranged acute lymphoblastic leukemias

    DEFF Research Database (Denmark)

    Andersson, Anna K; Ma, Jing; Wang, Jianmin;

    2015-01-01

    Infant acute lymphoblastic leukemia (ALL) with MLL rearrangements (MLL-R) represents a distinct leukemia with a poor prognosis. To define its mutational landscape, we performed whole-genome, exome, RNA and targeted DNA sequencing on 65 infants (47 MLL-R and 18 non-MLL-R cases) and 20 older childr...

  17. Synthesis of cycloheptanoid natural products via tandem 5-exo cyclization/Claisen rearrangement process

    OpenAIRE

    Ovaska, Timo V.

    2010-01-01

    This article describes the development of microwave-assisted oxyanionic 5-exo-dig cyclization-Claisen rearrangement sequence as a convenient “one-pot” route to a variety of seven-membered carbocyclic ring systems. This process was used as the key transformation for the construction of several natural products, including frondosins A, B, and C.

  18. A Pyrazole to Furan Rearrangement. Thermolysis of 5-Azido-4-formylpyrazoles

    DEFF Research Database (Denmark)

    Svenstrup, Niels; Simonsen, Klaus B.; Thorup, Niels;

    1999-01-01

    5-Azido-3-benzyl-4-formyl-1-phenylpyrazoles 1a-c extrude dinitrogen upon heating in toluene to give the corresponding nitrenes, which immediately rearrange via a new ring-opening ring-closure reaction to produce an equimolar mixture of 4-cyano-2-phenyl-3-phenylazofurans 2a-c and 3-benzyl-4-cyano-...

  19. Structure of Salvioccidentalin, a Diterpenoid with a Rearranged neo-Clerodane Skeleton from Salvia occidentalis

    OpenAIRE

    Jorge Cárdenas; José Antonio Morales-Serna; Bernardo Antonio Frontana-Uribe; Manuel Salmón; Miguel Ángel Jaime-Vasconcelos

    2011-01-01

    From the aerial parts of Salvia occidentalis (Labiatae) a new diterpenoid with a rearranged neo-clerodane skeleton was isolated. This new compound was named salvioccidentalin and its structure was established by spectroscopic means. A probable biogenetic relationship with salvigenolide from S. fulgens and salvileucalin A and spiroleucantholide from Salvia leucantha is proposed.

  20. ON THE PECULIARITIES OF THE RING CONTRACTION REACTIONS OF HOMODRIMANES VIA ACID MEDIATED EPOXIDE REARRANGEMENT

    Directory of Open Access Journals (Sweden)

    Veaceslav Kulciţki

    2011-06-01

    Full Text Available A selective rearrangement of a epoxy-homodrimanic substrate is described. Using fluorosulfonic acid at low temperature leads by ring contraction to a perhydrindanic structure. On the contrary, using boron trifluoride-diethyl ether at r.t. selectively brings about angular methyl migration.

  1. The rearrangement process in a two-stage broadcast switching network

    DEFF Research Database (Denmark)

    Jacobsen, Søren B.

    1988-01-01

    The rearrangement process in the two-stage broadcast switching network presented by F.K. Hwang and G.W. Richards (ibid., vol.COM-33, no.10, p.1025-1035, Oct. 1985) is considered. By defining a certain function it is possible to calculate an upper bound on the number of connections to be moved...

  2. Brönsted Acid of Keggin Type Polyoxometalate Catalyzed Pinacol Rearrangement

    Directory of Open Access Journals (Sweden)

    Aldes Lesbani

    2014-07-01

    Full Text Available Keggin type polyoxometalates K4[a-SiW12O40] was synthesized and transformed to H4[a-SiW12O40]. Both catalysts have been used for pinacol rearrangement in toluene at 373 oK. The results showed that reaction of pinacol rearrangement did not proceed using K4[a-SiW12O40] as catalyst. The extent reac-tion time until 20 h also did not produce pinacolone as main product. By using H4[a-SiW12O40] as cata-lyst at 1 h reaction time gave conversion 100% with formation of pinacolone 72%. The reaction produce 27% of 2,3-dimethyl-1,3-butadiene as byproduct and 99% carbon balance for the reaction. This phe-nomenon indicated the Brönsted acid is a key role for catalytic reaction of pinacol rearrangement to pinacolone. © 2014 BCREC UNDIP. All rightsSubmitted: 21st January 2014; Revised: 21st April 2014; Accepted: 3rd May 2014[ How to Cite: Lesbani, A., Mohadi, R., (2014. Brönsted Acid of Keggin Type Polyoxometalate Catalyzed Pinacol Rearrangement. Bulletin of Chemical Reaction Engineering & Catalysis, 9 (2: 136-141. (doi:10.9767/bcrec.9.2.6074.136-141 ][ Permalink/DOI: http://dx.doi.org/10.9767/bcrec.9.2.6074.136-141

  3. Synthesis of N-protected Galactosamine Building Blocks from D-Tagatose via the Heyns Rearrangement

    DEFF Research Database (Denmark)

    Wrodnigg, Tanja M.; Lundt, Inge; Stütz, Arnold E.

    2006-01-01

    N-Acetyl-D-galactosamine (11), a very important naturally occurring building block of oligosaccharides, is easily accessible via the Heyns rearrangement of D-tagatose (3) with benzylamine. The short and efficient synthesis of various differently N-protected D-galactosamine derivatives is reported....

  4. Long-term rearrangements of hippocampal mossy fiber terminal connectivity in the adult regulated by experience.

    Science.gov (United States)

    Galimberti, Ivan; Gogolla, Nadine; Alberi, Stefano; Santos, Alexandre Ferrao; Muller, Dominique; Caroni, Pico

    2006-06-01

    We investigated rearrangements of connectivity between hippocampal mossy fibers and CA3 pyramidal neurons. We found that mossy fibers establish 10-15 local terminal arborization complexes (LMT-Cs) in CA3, which exhibit major differences in size and divergence in adult mice. LMT-Cs exhibited two types of long-term rearrangements in connectivity in the adult: progressive expansion of LMT-C subsets along individual dendrites throughout life, and pronounced increases in LMT-C complexities in response to an enriched environment. In organotypic slice cultures, subsets of LMT-Cs also rearranged extensively and grew over weeks and months, altering the strength of preexisting connectivity, and establishing or dismantling connections with pyramidal neurons. Differences in LMT-C plasticity reflected properties of individual LMT-Cs, not mossy fibers. LMT-C maintenance and growth were regulated by spiking activity, mGluR2-sensitive transmitter release from LMTs, and PKC. Thus, subsets of terminal arborization complexes by mossy fibers rearrange their local connectivities in response to experience and age throughout life.

  5. Mapping of 5q35 chromosomal rearrangements within a genomically unstable region

    DEFF Research Database (Denmark)

    Buysse, Karen; Crepel, An; Menten, Björn;

    2008-01-01

    BACKGROUND: Recent molecular studies of breakpoints of recurrent chromosome rearrangements revealed the role of genomic architecture in their formation. In particular, segmental duplications representing blocks of >1 kb with >90% sequence homology were shown to mediate non-allelic homologous reco...

  6. Isolation of Betulin and Rearrangement to Allobetulin: A Biomimetic Natural Product Synthesis

    Science.gov (United States)

    Green, Brian; Bentley, Michael D.; Chung, Bong Y.; Lynch, Nicholas G.; Jensen, Bruce L.

    2007-01-01

    The triterpenes are a diverse class of widely distributed natural products derived from squalene. Various cyclization and subsequent rearrangement reactions produce many complex structural types. These compounds frequently display a wide divergence of biological properties. For example the pentacyclic triterpene, betulin, is isolated from white…

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

    Science.gov (United States)

    Emanuel, Beverly S.

    2008-01-01

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

  8. Enantioselective total synthesis of (+)-Lingzhiol via tandem semipinacol rearrangement/Friedel-Crafts type cyclization.

    Science.gov (United States)

    Chen, Dong; Xu, Wen-Dan; Liu, Hao-Miao; Li, Ming-Ming; Yan, Yong-Min; Li, Xiao-Nian; Li, Yan; Cheng, Yong-Xian; Qin, Hong-Bo

    2016-06-30

    Enantioselective total synthesis of (+)-Lingzhiol has been achieved. It is the first example of in tandem semipinacol rearrangement reactions, the migrated aryl group further reacting with the carbonyl oxonium electrophile to furnish a polycyclic skeleton. Our synthesis involves 13 steps and proceeds in 6% overall yield. PMID:27321202

  9. Screening for ALK Rearrangements in Lung Cancer: Time for a New Generation of Diagnostics?

    OpenAIRE

    Dagogo-Jack, Ibiayi; Shaw, Alice T.

    2016-01-01

    A study reported in this issue of The Oncologist examined the utility of next-generation sequencing (NGS) in detecting ALK rearrangements. NGS may one day become the standard initial test for molecular genotyping of patients with advanced cancers, and this new generation of ALK diagnostics is a welcome addition to the current screening repertoire.

  10. Structure of Salvioccidentalin, a Diterpenoid with a Rearranged neo-Clerodane Skeleton from Salvia occidentalis

    Directory of Open Access Journals (Sweden)

    Jorge Cárdenas

    2011-10-01

    Full Text Available From the aerial parts of Salvia occidentalis (Labiatae a new diterpenoid with a rearranged neo-clerodane skeleton was isolated. This new compound was named salvioccidentalin and its structure was established by spectroscopic means. A probable biogenetic relationship with salvigenolide from S. fulgens and salvileucalin A and spiroleucantholide from Salvia leucantha is proposed.

  11. DNA template strand sequencing of single-cells maps genomic rearrangements at high resolution

    NARCIS (Netherlands)

    Falconer, Ester; Hills, Mark; Naumann, Ulrike; Poon, Steven S. S.; Chavez, Elizabeth A.; Sanders, Ashley D.; Zhao, Yongjun; Hirst, Martin; Lansdorp, Peter M.

    2012-01-01

    DNA rearrangements such as sister chromatid exchanges (SCEs) are sensitive indicators of genomic stress and instability, but they are typically masked by single-cell sequencing techniques. We developed Strand-seq to independently sequence parental DNA template strands from single cells, making it po

  12. Gold(I)-Catalyzed Dearomative Rautenstrauch Rearrangement: Enantioselective Access to Cyclopenta[b]indoles

    Science.gov (United States)

    Zi, Weiwei; Wu, Hongmiao; Toste, F. Dean

    2016-01-01

    A highly enantioselective dearomative Rautenstrauch rearrangement catalyzed by cationic (S)-DTBM-Segphosgold(I) is reported. This reaction provides a straightforward method to prepare enantioenriched cyclopenta[b]indoles. These studies show vast difference in enantioselectivity in the reactions of propargyl acetates and propargyl acetals in the chiral ligand-controlled Rautenstrauch reaction. PMID:25710515

  13. A DFT exploration of the enantioselective rearrangement of cyclohexene oxide to cyclohexenol

    DEFF Research Database (Denmark)

    Brandt, Peter; Norrby, Per-Ola; Andersson, Pher G.

    2003-01-01

    In this paper, we present computational results for the (1S,3R,4R)-3-(pyrrolidinyl)-methyl-2-azabicyclo[2.2.1]heptane mediated rearrangement of cyclohexene oxide. The results nicely explain the differences in enantioselectivities between catalytic and stoichiometric mode between different ligands...

  14. Analyzing the CDR3 Repertoire with respect to TCR-Beta Chain V-D-J and V-J Rearrangements in Peripheral T Cells using HTS.

    Science.gov (United States)

    Ma, Long; Yang, Liwen; Bin Shi; He, Xiaoyan; Peng, Aihua; Li, Yuehong; Zhang, Teng; Sun, Suhong; Ma, Rui; Yao, Xinsheng

    2016-07-12

    V-D-J rearrangement of the TCR-beta chain follows the 12/23 rule and the beyond 12/23 restriction. Currently, the proportion and characteristics of TCR-beta chain V-J rearrangement is unclear. We used high-throughput sequencing to compare and analyze TCR-beta chain V-J rearrangement and V-D-J rearrangement in the CDR3 repertoires of T cells from the PBMCs of six volunteers and six BALB/c mice. The results showed that the percentage of V-J rearrangement of the volunteers was approximately 0.7%, whereas that of the mice was 2.2%. The clonality of mice V-J rearrangement was significantly reduced compared with the V-D-J rearrangement, whereas the clonality of human V-J rearrangement was slightly reduced compared with the V-D-J rearrangement. V-J rearrangement in CDR3 involved the significant usage of N, S, F and L, whereas V-D-J rearrangement in CDR3 involved the significant usage of R and G. The levels of V deletion and J deletion in V-J rearrangement were significantly reduced compared with V-D-J rearrangement. TRBD and TRBJ usage in V-J rearrangement differed from that of V-D-J rearrangement, including dominant usage of TRBV and TRBJ and their pairing. Taken together, these results provide new ideas and technology for studies of V-D-J rearrangement and V-J rearrangement in the CDR3 repertoire.

  15. Recurrent gene fusions in prostate cancer: their clinical implications and uses

    NARCIS (Netherlands)

    Hessels, D.; Schalken, J.A.

    2013-01-01

    Gene fusions, resulting from chromosomal rearrangements, have been attributed to leukaemias and soft tissue sarcomas. The recent discovery of a recurrent gene fusion TMPRSS2-ERG in approximately half of the prostate cancers tested indicates that gene fusions also play a role in the onset of common e

  16. Are ribosomal DNA clusters rearrangement hotspots? A case study in the genus Mus (Rodentia, Muridae

    Directory of Open Access Journals (Sweden)

    Douzery Emmanuel JP

    2011-05-01

    Full Text Available Abstract Background Recent advances in comparative genomics have considerably improved our knowledge of the evolution of mammalian karyotype architecture. One of the breakthroughs was the preferential localization of evolutionary breakpoints in regions enriched in repetitive sequences (segmental duplications, telomeres and centromeres. In this context, we investigated the contribution of ribosomal genes to genome reshuffling since they are generally located in pericentromeric or subtelomeric regions, and form repeat clusters on different chromosomes. The target model was the genus Mus which exhibits a high rate of karyotypic change, a large fraction of which involves centromeres. Results The chromosomal distribution of rDNA clusters was determined by in situ hybridization of mouse probes in 19 species. Using a molecular-based reference tree, the phylogenetic distribution of clusters within the genus was reconstructed, and the temporal association between rDNA clusters, breakpoints and centromeres was tested by maximum likelihood analyses. Our results highlighted the following features of rDNA cluster dynamics in the genus Mus: i rDNA clusters showed extensive diversity in number between species and an almost exclusive pericentromeric location, ii a strong association between rDNA sites and centromeres was retrieved which may be related to their shared constraint of concerted evolution, iii 24% of the observed breakpoints mapped near an rDNA cluster, and iv a substantial rate of rDNA cluster change (insertion, deletion also occurred in the absence of chromosomal rearrangements. Conclusions This study on the dynamics of rDNA clusters within the genus Mus has revealed a strong evolutionary relationship between rDNA clusters and centromeres. Both of these genomic structures coincide with breakpoints in the genus Mus, suggesting that the accumulation of a large number of repeats in the centromeric region may contribute to the high level of chromosome

  17. Reconstruction of ancestral chromosome architecture and gene repertoire reveals principles of genome evolution in a model yeast genus.

    Science.gov (United States)

    Vakirlis, Nikolaos; Sarilar, Véronique; Drillon, Guénola; Fleiss, Aubin; Agier, Nicolas; Meyniel, Jean-Philippe; Blanpain, Lou; Carbone, Alessandra; Devillers, Hugo; Dubois, Kenny; Gillet-Markowska, Alexandre; Graziani, Stéphane; Huu-Vang, Nguyen; Poirel, Marion; Reisser, Cyrielle; Schott, Jonathan; Schacherer, Joseph; Lafontaine, Ingrid; Llorente, Bertrand; Neuvéglise, Cécile; Fischer, Gilles

    2016-07-01

    Reconstructing genome history is complex but necessary to reveal quantitative principles governing genome evolution. Such reconstruction requires recapitulating into a single evolutionary framework the evolution of genome architecture and gene repertoire. Here, we reconstructed the genome history of the genus Lachancea that appeared to cover a continuous evolutionary range from closely related to more diverged yeast species. Our approach integrated the generation of a high-quality genome data set; the development of AnChro, a new algorithm for reconstructing ancestral genome architecture; and a comprehensive analysis of gene repertoire evolution. We found that the ancestral genome of the genus Lachancea contained eight chromosomes and about 5173 protein-coding genes. Moreover, we characterized 24 horizontal gene transfers and 159 putative gene creation events that punctuated species diversification. We retraced all chromosomal rearrangements, including gene losses, gene duplications, chromosomal inversions and translocations at single gene resolution. Gene duplications outnumbered losses and balanced rearrangements with 1503, 929, and 423 events, respectively. Gene content variations between extant species are mainly driven by differential gene losses, while gene duplications remained globally constant in all lineages. Remarkably, we discovered that balanced chromosomal rearrangements could be responsible for up to 14% of all gene losses by disrupting genes at their breakpoints. Finally, we found that nonsynonymous substitutions reached fixation at a coordinated pace with chromosomal inversions, translocations, and duplications, but not deletions. Overall, we provide a granular view of genome evolution within an entire eukaryotic genus, linking gene content, chromosome rearrangements, and protein divergence into a single evolutionary framework.

  18. Diagnosis of a constitutional five-chromosome rearrangement by fluorescent in situ hybridization (FISH)

    Energy Technology Data Exchange (ETDEWEB)

    Tsien, F.; Shapira, E. [Tulane Univ. School of Medicine, New Orleans, LA (United States); Carvalho, T. [Hospital Sarah Kubitschek, Brasilia (Brazil)] [and others

    1994-09-01

    Complex chromosomal rearrangements are structural rearrangements involving at least three chromosomes and three or more chromosome breakpoints. Such karyotypes are often acquired during cancer multi-step development and in chromosome instability syndromes. However, extremely rare constitutional forms have been reported, most of which are incompatible with life. We present a 2-year-old female with de novo complex rearrangement consisting of five chromosomes and nine breakpoints. Clinical evaluation at two years of age revealed a weight of 5 kg, length of 66 cm, and had circumference of 38 cm, all below the 5th percentile, microcephaly, trigonocephaly, epicanthal folds, inguinal hernia, left clubfoot, hypertonicity, and developmental delay. The neurological examination revealed chorea-acanthocytosis and psychomotor delay. Cultured lymphocytes and fibroblasts revealed a karyotype consisting of five derivative chromosomes. The metaphases were further analyzed by FISH using chromosome-specific libraries and telomeric probes in order to delineate the composition of the rearranged chromosomes; FISH results demonstrated a karyotype of: 46,XX,1pter{r_arrow}1q25::1q42.1{r_arrow}1qter, 2pter{r_arrow}q32.3::1q32.3{r_arrow}2q41::2q37.3{r_arrow}2qter, 7qter{r_arrow}7q21.2::6q22.3{r_arrow}6qter::1q31{r_arrow}1q32.3::6p23{r_arrow}6q22.3, 7pter{r_arrow}7q21.1::6p23{r_arrow}6pter, 2q33{r_arrow}2q37, 1::9p21{r_arrow}9qter. This analysis demonstrates the usefulness of FISH in characterizing complex chromosome rearrangements otherwise difficult to correctly interpret using classical cytogenetics alone.

  19. Simulated Microgravity Induced Cytoskeletal Rearrangements are Modulated by Protooncogenes

    Science.gov (United States)

    Melhado, C. D.; Sanford, G. L.; Bosah, F.; Harris-Hooker, S.

    1998-01-01

    Microgravity is the environment living systems encounter during space flight and gravitational unloading is the effect of this environment on living systems. The cell, being a multiphasic chemical system, is a useful starting point to study the potential impact of gravity unloading on physiological function. In the absence of gravity, sedimentation of organelles including chromosomes, mitochondria, nuclei, the Golgi apparatus, vacuoles, and the endoplasmic reticulum may be affected. Most of these organelles, however, are somewhat held in place by cytoskeleton. Hansen and Igber suggest that intermediate filaments act to stabilize the nuleus against rotational movement, and integrate cell and nuclear structure. The tensegrity theory supports the idea that mechanical or physical forces alters the cytoskeletal structures of a cell resulting in the changes in cell: matrix interactions and receptor-signaling coupling. This type of stress to the cytoskeleton may be largely responsible regulating cell shape, growth, movement and metabolism. Mouse MC3T3 El cells under microgravity exhibited significant cytoskeletal changes and alterations in cell growth. The alterations in cytoskeleton architecture may be due to changes in the expression of actin related proteins or integrins. Philopott and coworkers reported on changes in the distribution of microtubule and cytoskeleton elements in the cells of heart tissue from space flight rats and those centrifuged at 1.7g. Other researchers have showed that microgravity reduced EGF-induced c-fos and c-jun expression compared to 1 g controls. Since c-fos and c-jun are known regulators of cell growth, it is likely that altered signal transduction involving protooncogenes may play a crucial role in the reduced growth and alterations in cytoskeletal arrangements found during space flight. It is clear that a microgravity environment induces a number of changes in cell shape, cell surface molecules, gene expression, and cytoskeletal

  20. Severe acute interstitial lung disease in a patient with anaplastic lymphoma kinase rearrangement-positive non-small cell lung cancer treated with alectinib.

    Science.gov (United States)

    Yamamoto, Yuzo; Okamoto, Isamu; Otsubo, Kohei; Iwama, Eiji; Hamada, Naoki; Harada, Taishi; Takayama, Koichi; Nakanishi, Yoichi

    2015-10-01

    Alectinib, the second generation anaplastic lymphoma kinase (ALK) inhibitor, has significant potency in patients with ALK rearrangement positive non-small cell lung cancer (NSCLC), and its toxicity is generally well tolerable. We report a patient who developed severe acute interstitial lung disease after alectinib treatment. An 86-year-old woman with stage IV lung adenocarcinoma positive for rearrangement of ALK gene was treated with alectinib. On the 215th day after initiation of alectinib administration, she was admitted to our hospital with the symptom of progressive dyspnea. Computed tomography (CT) revealed diffuse ground glass opacities and consolidations in both lungs, and analysis of bronchoalveolar lavage fluid revealed pronounced lymphocytosis. There was no evidence of infection or other specific causes of her condition, and she was therefore diagnosed with interstitial lung disease induced by alectinib. Her CT findings and respiratory condition improved after steroid pulse therapy. As far as we are aware, this is the first reported case of alectinib-induced severe interstitial lung disease (ILD). We should be aware of the possibility of such a severe adverse event and should therefore carefully monitor patients treated with this drug.

  1. [Genome Rearrangements in Azospirillum brasilense Sp7 with the Involvement of the Plasmid pRhico and the Prophage phiAb-Cd].

    Science.gov (United States)

    Katsy, E I; Petrova, L P

    2015-12-01

    Alphaproteobacteria of the species Azospirillum brasilense have a multicomponent genome that undergoes frequent spontaneous rearrangements, yielding changes in the plasmid profiles of strains. Specifically, variants (Cd, Sp7.K2, Sp7.1, Sp7.4, Sp7.8, etc.) of the type strainA. brasilense Sp7 that had lost a 115-MDa plasmid were previously selected. In many of them, the molecular weight of a 90-MDa plasmid (p90 or pRhico), which is a kind of "depot" for glycopolymer biosynthesis genes, increased. In this study, a collection of primers was designed to the plasmid pRhico and to the DNA of prophage phiAb-Cd integrated in it. The use ofthese primers in polymerase chain reactions allowed the detection of the probable excision of phiAb-Cd phage from the DNA of A. brasilense variants Sp7.4 and Sp7.8 and other alterations of the pRhico structure in A. brasilense strains Cd, Sp7.K2, and Sp7.8. The developed primers and PCR conditions may be recoin mended for primary analysis of spontaneous plasmid rearrangements in A. brasilense Sp7 and related strains.

  2. Markov State Models Reveal a Two-Step Mechanism of miRNA Loading into the Human Argonaute Protein: Selective Binding followed by Structural Re-arrangement

    KAUST Repository

    Jiang, Hanlun

    2015-07-16

    Argonaute (Ago) proteins and microRNAs (miRNAs) are central components in RNA interference, which is a key cellular mechanism for sequence-specific gene silencing. Despite intensive studies, molecular mechanisms of how Ago recognizes miRNA remain largely elusive. In this study, we propose a two-step mechanism for this molecular recognition: selective binding followed by structural re-arrangement. Our model is based on the results of a combination of Markov State Models (MSMs), large-scale protein-RNA docking, and molecular dynamics (MD) simulations. Using MSMs, we identify an open state of apo human Ago-2 in fast equilibrium with partially open and closed states. Conformations in this open state are distinguished by their largely exposed binding grooves that can geometrically accommodate miRNA as indicated in our protein-RNA docking studies. miRNA may then selectively bind to these open conformations. Upon the initial binding, the complex may perform further structural re-arrangement as shown in our MD simulations and eventually reach the stable binary complex structure. Our results provide novel insights in Ago-miRNA recognition mechanisms and our methodology holds great potential to be widely applied in the studies of other important molecular recognition systems.

  3. Novel microduplications at Xp11.22 including HUWE1: clinical and molecular insights into these genomic rearrangements associated with intellectual disability.

    Science.gov (United States)

    Santos-Rebouças, Cíntia Barros; de Almeida, Luciana Guedes; Belet, Stefanie; Dos Santos, Suely Rodrigues; Ribeiro, Márcia Gonçalves; da Silva, Antônio Francisco Alves; Medina-Acosta, Enrique; Dos Santos, Jussara Mendonça; Gonçalves, Andressa Pereira; Bahia, Paulo Roberto Valle; Pimentel, Márcia Mattos Gonçalves; Froyen, Guy

    2015-04-01

    Recently, we defined a minimal overlapping region for causal Xp11.22 copy number gains in males with intellectual disability (ID), and identified HECT, UBA and WWE domain-containing protein-1 (HUWE1) as the primary dosage-sensitive gene, whose overexpression leads to ID. In the present study, we used this minimal interval to search for HUWE1 copy number variations by quantitative polymerase chain reaction in a large cohort of Brazilian males with idiopathic ID. We detected two unrelated sporadic individuals with syndromic ID carrying unique overlapping duplications encompassing HUWE1. Breakpoint junction analysis showed a simple tandem duplication in the first patient, which has probably arisen by microhomology-mediated break-induced repair mechanism. In the second patient, the rearrangement is complex having an insertion of an intrachromosomal sequence at its junction. This kind of rearrangement has not been reported in Xp11.22 duplications and might have emerged by a replication- or recombination-based mechanism. Furthermore, the presence of infantile seizures in the second family suggests a potential role of increased KDM5C expression on epilepsy. Our findings highlight the importance of microduplications at Xp11.22 to ID, even in sporadic cases, and reveal new clinical and molecular insight into HUWE1 copy number gains.

  4. Reconstruction of the ancestral plastid genome in Geraniaceae reveals a correlation between genome rearrangements, repeats, and nucleotide substitution rates.

    Science.gov (United States)

    Weng, Mao-Lun; Blazier, John C; Govindu, Madhumita; Jansen, Robert K

    2014-03-01

    Geraniaceae plastid genomes are highly rearranged, and each of the four genera already sequenced in the family has a distinct genome organization. This study reports plastid genome sequences of six additional species, Francoa sonchifolia, Melianthus villosus, and Viviania marifolia from Geraniales, and Pelargonium alternans, California macrophylla, and Hypseocharis bilobata from Geraniaceae. These genome sequences, combined with previously published species, provide sufficient taxon sampling to reconstruct the ancestral plastid genome organization of Geraniaceae and the rearrangements unique to each genus. The ancestral plastid genome of Geraniaceae has a 4 kb inversion and a reduced, Pelargonium-like small single copy region. Our ancestral genome reconstruction suggests that a few minor rearrangements occurred in the stem branch of Geraniaceae followed by independent rearrangements in each genus. The genomic comparison demonstrates that a series of inverted repeat boundary shifts and inversions played a major role in shaping genome organization in the family. The distribution of repeats is strongly associated with breakpoints in the rearranged genomes, and the proportion and the number of large repeats (>20 bp and >60 bp) are significantly correlated with the degree of genome rearrangements. Increases in the degree of plastid genome rearrangements are correlated with the acceleration in nonsynonymous substitution rates (dN) but not with synonymous substitution rates (dS). Possible mechanisms that might contribute to this correlation, including DNA repair system and selection, are discussed. PMID:24336877

  5. Chromosomal Rearrangements in Post-Chernobyl Papillary Thyroid Carcinomas: Evaluation by Spectral Karyotyping and Automated Interphase FISH

    Directory of Open Access Journals (Sweden)

    Ludwig Hieber

    2011-01-01

    Full Text Available Structural genomic rearrangements are frequent findings in human cancers. Therefore, papillary thyroid carcinomas (PTCs were investigated for chromosomal aberrations and rearrangements of the RET proto-oncogene. For this purpose, primary cultures from 23 PTC have been established and metaphase preparations were analysed by spectral karyotyping (SKY. In addition, interphase cell preparations of the same cases were investigated by fluorescence in situ hybridisation (FISH for the presence of RET/PTC rearrangements using RET-specific DNA probes. SKY analysis of PTC revealed structural aberrations of chromosome 11 and several numerical aberrations with frequent loss of chromosomes 20, 21, and 22. FISH analysis for RET/PTC rearrangements showed prevalence of this rearrangement in 72% (16 out of 22 of cases. However, only subpopulations of tumour cells exhibited this rearrangement indicating genetic heterogeneity. The comparison of visual and automated scoring of FISH signals revealed concordant results in 19 out of 22 cases (87% indicating reliable scoring results using the optimised scoring parameter for RET/PTC with the automated Metafer4 system. It can be concluded from this study that genomic rearrangements are frequent in PTC and therefore important events in thyroid carcinogenesis.

  6. A screen for suppressors of gross chromosomal rearrangements identifies a conserved role for PLP in preventing DNA lesions.

    Directory of Open Access Journals (Sweden)

    Pamela Kanellis

    2007-08-01

    Full Text Available Genome instability is a hallmark of cancer cells. One class of genome aberrations prevalent in tumor cells is termed gross chromosomal rearrangements (GCRs. GCRs comprise chromosome translocations, amplifications, inversions, deletion of whole chromosome arms, and interstitial deletions. Here, we report the results of a genome-wide screen in Saccharomyces cerevisiae aimed at identifying novel suppressors of GCR formation. The most potent novel GCR suppressor identified is BUD16, the gene coding for yeast pyridoxal kinase (Pdxk, a key enzyme in the metabolism of pyridoxal 5' phosphate (PLP, the biologically active form of vitamin B6. We show that Pdxk potently suppresses GCR events by curtailing the appearance of DNA lesions during the cell cycle. We also show that pharmacological inhibition of Pdxk in human cells leads to the production of DSBs and activation of the DNA damage checkpoint. Finally, our evidence suggests that PLP deficiency threatens genome integrity, most likely via its role in dTMP biosynthesis, as Pdxk-deficient cells accumulate uracil in their nuclear DNA and are sensitive to inhibition of ribonucleotide reductase. Since Pdxk links diet to genome stability, our work supports the hypothesis that dietary micronutrients reduce cancer risk by curtailing the accumulation of DNA damage and suggests that micronutrient depletion could be part of a defense mechanism against hyperproliferation.

  7. Rotavirus rearranged genomic RNA segments are preferentially packaged into viruses despite not conferring selective growth advantage to viruses.

    Directory of Open Access Journals (Sweden)

    Cécile Troupin

    Full Text Available The rotavirus (RV genome consists of 11 double-stranded RNA segments. Sometimes, partial sequence duplication of an RNA segment leads to a rearranged RNA segment. To specify the impact of rearrangement, the replication efficiencies of human RV with rearranged segments 7, 11 or both were compared to these of the homologous human wild-type RV (wt-RV and of the bovine wt-RV strain RF. As judged by viral growth curves, rotaviruses with a rearranged genome (r-RV had no selective growth advantage over the homologous wt-RV. In contrast, r-RV were selected over wt-RV during competitive experiments (i.e mixed infections between r-RV and wt-RV followed by serial passages in cell culture. Moreover, when competitive experiments were performed between a human r-RV and the bovine wt-RV strain RF, which had a clear growth advantage, rearranged segments 7, 11 or both always segregated in viral progenies even when performing mixed infections at an MOI ratio of 1 r-RV to 100 wt-RV. Lastly, bovine reassortant viruses that had inherited a rearranged segment 7 from human r-RV were generated. Although substitution of wt by rearranged segment 7 did not result in any growth advantage, the rearranged segment was selected in the viral progenies resulting from mixed infections by bovine reassortant r-RV and wt-RV, even for an MOI ratio of 1 r-RV to 10(7 wt-RV. Lack of selective growth advantage of r-RV over wt-RV in cell culture suggests a mechanism of preferential packaging of the rearranged segments over their standard counterparts in the viral progeny.

  8. Towards a Catalytic Asymmetric Cope Rearrangement and the Synthesis and Self-Assembly of Metal-Coordinated Hosts

    OpenAIRE

    Moehlig, Melissa Padilla

    2013-01-01

    The Cope rearrangement has been used as the key step of several natural products but to date there is only one limited example in the literature that is capable of performing an asymmetric variant of this reaction. The first half of this dissertation focuses on our efforts towards performing a catalytic asymmetric Cope rearrangement to access remote stereocenters. The rearrangement of 2-formyl-1,5-dienes was achieved with both Brønsted and Lewis acid catalysts. The best Lewis acid catalyst wa...

  9. MYC-IG rearrangements are negative predictors of survival in DLBCL patients treated with immunochemotherapy: a GELA/LYSA study.

    Science.gov (United States)

    Copie-Bergman, Christiane; Cuillière-Dartigues, Peggy; Baia, Maryse; Briere, Josette; Delarue, Richard; Canioni, Danielle; Salles, Gilles; Parrens, Marie; Belhadj, Karim; Fabiani, Bettina; Recher, Christian; Petrella, Tony; Ketterer, Nicolas; Peyrade, Frederic; Haioun, Corinne; Nagel, Inga; Siebert, Reiner; Jardin, Fabrice; Leroy, Karen; Jais, Jean-Philippe; Tilly, Herve; Molina, Thierry Jo; Gaulard, Philippe

    2015-11-26

    Diffuse large B-cell lymphoma (DLBCL) with MYC rearrangement (MYC-R) carries an unfavorable outcome. We explored the prognostic value of the MYC translocation partner gene in a series of MYC-R de novo DLBCL patients enrolled in first-line prospective clinical trials (Groupe d'Etudes des Lymphomes de l'Adulte/Lymphoma Study Association) and treated with rituximab-anthracycline-based chemotherapy. A total of 774 DLBCL cases characterized for cell of origin by the Hans classifier were analyzed using fluorescence in situ hybridization with BCL2, BCL6, MYC, immunoglobulin (IG)K, and IGL break-apart and IGH/MYC, IGK/MYC, and IGL/MYC fusion probes. MYC-R was observed in 51/574 (8.9%) evaluable DLBCL cases. MYC-R cases were predominantly of the germinal center B-cell-like subtype 37/51 (74%) with no distinctive morphologic and phenotypic features. Nineteen cases were MYC single-hit and 32 cases were MYC double-hit (MYC plus BCL2 and/or BCL6) DLBCL. MYC translocation partner was an IG gene in 24 cases (MYC-IG) and a non-IG gene (MYC-non-IG) in 26 of 50 evaluable cases. Noteworthy, MYC-IG patients had shorter overall survival (OS) (P = .0002) compared with MYC-negative patients, whereas no survival difference was observed between MYC-non-IG and MYC-negative patients. In multivariate analyses, MYC-IG predicted poor progression-free survival (P = .0051) and OS (P = .0006) independently from the International Prognostic Index and the Hans classifier. In conclusion, we show in this prospective randomized trial that the adverse prognostic impact of MYC-R is correlated to the MYC-IG translocation partner gene in DLBCL patients treated with immunochemotherapy. These results may have an important impact on the clinical management of DLBCL patients with MYC-R who should be routinely characterized according to MYC partner gene. These trials are individually registered at www.clinicaltrials.gov as #NCT00144807, #NCT01087424, #NCT00169143, #NCT00144755, #NCT00140660, #NCT00140595, and

  10. A symplectic rearrangement of the four dimensional non-geometric scalar potential

    CERN Document Server

    Shukla, Pramod

    2015-01-01

    We present a symplectic rearrangement of the effective four-dimensional non-geometric scalar potential resulting from the type IIB superstring compactification on Calabi Yau orientifolds. The strategy has two main steps. In the first step, we rewrite the four dimensional scalar potential utilizing some interesting flux combinations which we call {\\it new generalized flux orbits}. After invoking a couple of non-trivial symplectic relations, in the second step, we further rearrange all the pieces of scalar potential into a completely `symplectic-formulation' which involves only the symplectic ingredients (such as period matrix etc.) without the need of knowing Calabi Yau metric. Moreover, the scalar potential under consideration is induced by a generic tree level K\\"{a}hler potential and (non-geometric) flux superpotential for arbitrary numbers of complex structure moduli, K\\"ahler moduli and odd-axions. Finally, we exemplify our symplectic formulation for the two well known toroidal examples based on type IIB ...

  11. Reaction of selected carbohydrate aldehydes with benzylmagnesium halides: benzyl versus o-tolyl rearrangement

    Directory of Open Access Journals (Sweden)

    Maroš Bella

    2014-08-01

    Full Text Available The Grignard reaction of 2,3-O-isopropylidene-α-D-lyxo-pentodialdo-1,4-furanoside and benzylmagnesium chloride (or bromide afforded a non-separable mixture of diastereomeric benzyl carbinols and diastereomeric o-tolyl carbinols. The latter resulted from an unexpected benzyl to o-tolyl rearrangement. The proportion of benzyl versus o-tolyl derivatives depended on the reaction conditions. Benzylmagnesium chloride afforded predominantly o-tolyl carbinols while the application of benzylmagnesium bromide led preferably to the o-tolyl carbinols only when used in excess or at higher temperatures. The structures of the benzyl and o-tolyl derivatives were confirmed unambiguously by NMR spectral data and X-ray crystallographic analysis of their 5-ketone analogues obtained by oxidation of the corresponding mixture of diastereomeric carbinols. A possible mechanism for the Grignard reaction leading to the benzyl→o-tolyl rearrangement is also proposed.

  12. Dynamic force measurement of rearrangements in a 2D network of droplets

    Science.gov (United States)

    Barkley, Solomon; Backholm, Matilda; Dalnoki-Veress, Kari

    2015-03-01

    The interaction between two liquid droplets in an immiscible liquid is well understood. However, the emulsions relevant to biological and industrial processes involve high concentrations of these droplets, and multi-body effects cannot be ignored. As droplets rearrange in response to a disturbance, the importance of individual pair-wise interactions between droplets changes with the geometry of neighbours. Here we report on an experimental setup consisting of a two- dimensional network of monodisperse droplets stabilized with a surfactant. The system is studied with micropipette deflection, which permits direct measurement of forces along with simultaneous imaging of the droplet network. One micropipette is used to apply a tensile or compressive force to the droplet cluster, while a second pipette acts as a force-transducing cantilever, deflecting in response to rearrangements of the droplets.

  13. Formal Total Synthesis of Diazonamide A by Indole Oxidative Rearrangement.

    Science.gov (United States)

    David, Nadège; Pasceri, Raffaele; Kitson, Russell R A; Pradal, Alexandre; Moody, Christopher J

    2016-07-25

    A short formal total synthesis of the marine natural product diazonamide A is described. The route is based on indole oxidative rearrangement, and a number of options were investigated involving migration of tyrosine or oxazole fragments upon oxidation of open chain or macrocyclic precursors. The final route proceeds from 7-bromoindole by sequential palladium-catalysed couplings of an oxazole fragment at C-2, followed by a tyrosine fragment at C-3. With the key 2,3-disubstituted indole readily in hand, formation of a macrocyclic lactam set the stage for the crucial oxidative rearrangement to a 3,3-disubstituted oxindole. Notwithstanding the concomitant formation of the unwanted indoxyl isomer, the synthesis successfully delivered, after deprotection, the key oxindole intermediate, thereby completing a formal total synthesis of diazonamide A. PMID:27346186

  14. Aza Cope Rearrangement of Propargyl Enammonium Cations Catalyzed By a Self-Assembled `Nanozyme

    Energy Technology Data Exchange (ETDEWEB)

    Hastings, Courntey J.; Fiedler, Dorothea; Bergman, Robert G.; Raymond, Kenneth N.

    2008-02-27

    The tetrahedral [Ga{sub 4}L{sub 6}]{sup 12-} assembly (L = N,N-bis(2,3-dihydroxybenzoyl)-1,5-diaminonaphthalene) encapsulates a variety of cations, including propargyl enammonium cations capable of undergoing the aza Cope rearrangement. For propargyl enammonium substrates that are encapsulated in the [Ga{sub 4}L{sub 6}]{sup 12-} assembly, rate accelerations of up to 184 are observed when compared to the background reaction. After rearrangement, the product iminium ion is released into solution and hydrolyzed allowing for catalytic turnover. The activation parameters for the catalyzed and uncatalyzed reaction were determined, revealing that a lowered entropy of activation is responsible for the observed rate enhancements. The catalyzed reaction exhibits saturation kinetics; the rate data obey the Michaelis-Menten model of enzyme kinetics, and competitive inhibition using a non-reactive guest has been demonstrated.

  15. A Wittig-olefination–Claisen-rearrangement approach to the 3-methylquinoline-4-carbaldehyde synthesis

    Directory of Open Access Journals (Sweden)

    Mukund G. Kulkarni

    2012-10-01

    Full Text Available Efficient syntheses are described for the synthetically important 3-methylquinoline-4-carbaldehydes 6a–h from o-nitrobenzaldehydes 1a–h employing a Wittig-olefination–Claisen-rearrangement protocol. The Wittig reaction of o-nitrobenzaldehydes with crotyloxymethylene triphenylphosphorane afforded crotyl vinyl ethers 2a–h, which on heating under reflux in xylene underwent Claisen rearrangement to give 4-pentenals 3a–h. Protection of the aldehyde group of the 4-pentenals as acetals 4a–h and subsequent oxidative cleavage of the terminal olefin furnished nitroaldehydes 5a–h. Reductive cyclization of these nitroaldehydes yielded the required 3-methylquinoline-4-carbaldehydes 6a–h in excellent yields. Therefore, an efficient method was developed for the preparation of 3-methylquinoline-4-carbaldehydes from o-nitrobenzaldehydes in a simple five-step procedure.

  16. Coupled-rearrangement-channels calculation of the three-body system under the absorbing boundary condition

    Directory of Open Access Journals (Sweden)

    Iwasaki M.

    2016-01-01

    Full Text Available We formulate the absorbing boundary condition (ABC in the coupled rearrangement-channels variational method (CRCVM for the three-body problem. The absorbing potential is introduced in the system of the identical three-bosons, on which the boson symmetry is explicitly imposed by considering the rearrangement channels. The resonance parameters and the strength of the monopole breakup are calculated by the CRCVM + ABC method, and the results are compared with the complex scaling method (CSM. We have found that the results of the ABC method are consistent with the CSM results. The effect of the boson symmetry, which is often neglected in the calculation of the triple α reactions, is also discussed.

  17. Gas-Phase Beckmann Rearrangement of Cyclohexanone Oxime over B-ZSM-5 Derived Titanosilicalite

    Institute of Scientific and Technical Information of China (English)

    尹双凤; 张法智; 徐柏庆

    2002-01-01

    Four different ZSM-5 zeolites are tested for the gas-phase Beckmann rearrangement of cyclohexanone oxime (CHO) into lactam. B-ZSM-5 derived titanosilicalite (Ti-ZSM-5) exhibits catalytic performances comparable to hydrothermally synthesized titanosilicalite (TS-1), much better than B-ZSM-5 and Al-ZSM-5. The effect of reaction conditions (solvent, feed space velocity, and water) on the catalytic performance of Ti-ZSM-5 is studied. It is found that a quantitative relationship exists among the feed space velocity, the reaction time, and the CHO constant conversion. Ethanol or methanol as solvent shows higher activity, lactam selectivity, and stability than benzene and n-hexanol. The addition of water to the rearrangement with a maximum amount of 1.0 mole per mole CHO results in the increase of CHO conversion while no meaningful changes in lactam selectivity and stability are observed.

  18. Unusual rearrangement in the photochemical addition of bis(alkylidene)disilacyclobutanes to C[sub 60

    Energy Technology Data Exchange (ETDEWEB)

    Kusukawa, Takahiro; Kabe, Yoshio; Erata, Tomoki; Nestler, B.; Ando, Wataru (Univ. of Tsukuba (Japan))

    1994-11-01

    The photochemical reaction of bis(alkylidene)-disilacyclobutanes 1a, b with C[sub 60] afforded the stable 1:1 adducts 3a,b, resulting from an unexpected rearrangement of the disilacyclobutane unit. The structures of 3a,b were determined by spectroscopic methods, including [sup 29]Si-[sup 1]H HMBC hetero nuclear shift correlation experiments. 18 refs., 2 figs.

  19. Influence of the dispersity of anthracite on the rearrangement of its structure during heat treatment

    Energy Technology Data Exchange (ETDEWEB)

    Fialkov, A.S.; Abramov, A.V.; Chuparova, L.D.; Kirilin, N.S.; Semenov, M.V.; Suslina, V.I.; Yurkovskii, I.M.

    1983-01-01

    The influence of the dispersity of anthracite on the rearrangement of its structure and its absorption capacity with respect to a binder has been investigated. It has been shown that a composition based on anthracite with a high degree of ordering of the structure can be obtained if the specific surface of the powder is not less than 14 m/sup 2//g but not more than 20 m/sup 2//g.

  20. The constitutional t(11;22): implications for a novel mechanism responsible for gross chromosomal rearrangements

    OpenAIRE

    Kurahashi, H; Inagaki, H; Ohye, T; Kogo, H.; Tsutsumi, M.; Kato, T.; Tong, M.; Emanuel, BS

    2010-01-01

    The constitutional t(11;22)(q23;q11) is the most common recurrent non-Robertsonian translocation in humans. The breakpoint sequences of both chromosomes are characterized by several hundred base pairs of palindromic AT-rich repeats (PATRRs). Similar PATRRs have also been identified at the breakpoints of other nonrecurrent translocations, suggesting that PATRR-mediated chromosomal translocation represents one of the universal pathways for gross chromosomal rearrangement in the human genome. We...

  1. Computational strategies and improvements in the linear algebraic variational approach to rearrangement scattering

    Science.gov (United States)

    Schwenke, David W.; Mladenovic, Mirjana; Zhao, Meishan; Truhlar, Donald G.; Sun, Yan

    1988-01-01

    The computational steps in calculating quantum mechanical reactive scattering amplitudes by the L2 generalized Newton variational principle are discussed with emphasis on computational strategies and recent improvements that make the calculations more efficient. Special emphasis is placed on quadrature techniques, storage management strategies, use of symmetry, and boundary conditions. It is concluded that an efficient implementation of these procedures provides a powerful algorithm for the accurate solution of the Schroedinger equation for rearrangements.

  2. RET-rearranged non-small-cell lung carcinoma: a clinicopathological and molecular analysis

    OpenAIRE

    Tsuta, K; Kohno, T.; Yoshida, A.; Shimada, Y.; Asamura, H.; Furuta, K; Kushima, R

    2014-01-01

    Background: To elucidate clinicopathological characteristics of non-small-cell lung carcinoma (NSCLC) cases carrying RET rearrangements causing oncogenic fusions to identify responders to therapy with RET tyrosine kinase inhibitors. Methods: We investigated 1874 patients with carcinomas, including 1620 adenocarcinomas (ADCs), 203 squamous cell carcinomas (SCCs), 8 large cell carcinomas, and 43 sarcomatoid carcinomas (SACs). Fluorescence in situ hybridisation (FISH) and/or reverse transcriptio...

  3. Fine mapping of V(D)J recombinase mediated rearrangements in human lymphoid malignancies

    OpenAIRE

    Halper-Stromberg, Eitan; Steranka, Jared; Giraldo-Castillo, Nicolas; Fuller, Timothy; Desiderio, Stephen; Burns, Kathleen H.

    2013-01-01

    Background Lymphocytes achieve diversity in antigen recognition in part by rearranging genomic DNA at loci encoding antibodies and cell surface receptors. The process, termed V(D)J recombination, juxtaposes modular coding sequences for antigen binding. Erroneous recombination events causing chromosomal translocations are recognized causes of lymphoid malignancies. Here we show a hybridization based method for sequence enrichment can be used to efficiently and selectively capture genomic DNA a...

  4. Chromothripsis-like chromosomal rearrangements induced by ionizing radiation using proton microbeam irradiation system

    OpenAIRE

    Morishita, Maki; Muramatsu, Tomoki; Suto, Yumiko; Hirai, Momoki; Konishi, Teruaki; Hayashi, Shin; Shigemizu, Daichi; Tsunoda, Tatsuhiko; Moriyama, Keiji; Inazawa, Johji

    2016-01-01

    Chromothripsis is the massive but highly localized chromosomal rearrangement in response to a one-step catastrophic event, rather than an accumulation of a series of subsequent and random alterations. Chromothripsis occurs commonly in various human cancers and is thought to be associated with increased malignancy and carcinogenesis. However, the causes and consequences of chromothripsis remain unclear. Therefore, to identify the mechanism underlying the generation of chromothripsis, we invest...

  5. Maternal effect mutations of the sponge locus affect actin cytoskeletal rearrangements in Drosophila melanogaster embryos

    OpenAIRE

    1992-01-01

    In the syncytial blastoderm stage of Drosophila embryogenesis, dome- shaped actin "caps" are observed above the interphase nuclei. During mitosis, this actin rearranges to participate in the formation of pseudocleavage furrows, transient membranous invaginations between dividing nuclei. Embryos laid by homozygous sponge mothers lack these characteristic actin structures, but retain other actin associated structures and processes. Our results indicate that the sponge product is specifically re...

  6. An alignment-free method to find and visualise rearrangements between pairs of DNA sequences

    OpenAIRE

    Pratas, Diogo; Silva, Raquel M; Pinho, Armando J.; Ferreira, Paulo J.S.G.

    2015-01-01

    Species evolution is indirectly registered in their genomic structure. The emergence and advances in sequencing technology provided a way to access genome information, namely to identify and study evolutionary macro-events, as well as chromosome alterations for clinical purposes. This paper describes a completely alignment-free computational method, based on a blind unsupervised approach, to detect large-scale and small-scale genomic rearrangements between pairs of DNA sequences. To illustrat...

  7. Hapmnioides A-C, Rearranged Labdane-Type Diterpenoids from the Chinese Liverwort Haplomitrium mnioides.

    Science.gov (United States)

    Zhou, Jinchuan; Zhang, Jiaozhen; Li, Ruijuan; Liu, Jun; Fan, Peihong; Li, Yi; Ji, Mei; Dong, Yiwen; Yuan, Huiqing; Lou, Hongxiang

    2016-09-01

    Many exceptional labdane-type diterpenoids have been exclusively found in liverworts, which serve as taxonomic molecules or play important ecological roles in interactions among organisms. Three unprecedented labdane-type diterpenoids hapmnioides A (1), B (2), and C (3) formed through cascade rearrangement from the Chinese liverwort Haplomitrium mnioides are reported. Their structures were established by comprehensive spectroscopic analysis coupled with single-crystal X-ray diffraction, and their anti-inflammatory activities were also preliminarily tested. PMID:27513610

  8. Cascade Wittig reaction-double Claisen and Cope rearrangements: one-pot synthesis of diprenylated coumarins gravelliferone, balsamiferone, and 6,8-diprenylumbelliferone

    Digital Repository Service at National Institute of Oceanography (India)

    Patre, R.E.; Shet, J.B.; Parameswaran, P.S.; Tilve, S.G.

    of the ethyl cinnamate 6 could undergo preferential Claisen-Cope rearrangement over 4’-prenyloxy group due to steric crowding during the formation of 1 via 7-prenyloxy-6-prenyl coumarin 8, a well known intermediate 11 for the synthesis of gravelliferone... rearrangement (Cope rearrangement) via route a (Scheme 3) to form intermediate 7, which on cyclisation forms pyran ring 8. The second Claisen rearrangement of the 7’-prenyloxycoumarin 8 to form 13, followed by two consecutive Cope rearrangements gives 1 via...

  9. 1p36.32 rearrangements and the role of PI-PLC η2 in nervous tumours.

    Science.gov (United States)

    Lo Vasco, Vincenza Rita

    2011-07-01

    Deletions in the distal region of the short arm of chromosome 1 (1p36) are widely diffuse, both in congenital 1p36 Deletion Syndrome and as somatic abnormalities in tumours. Rearrangements in 1p36 have been described in a broad spectrum of human neoplasias in addition to other chromosomal abnormalities. In neuroblastomas, wide hemizygous deletions in 1p36.23-1p36.32 have been described suggesting that the 1p36 region contains a tumour-suppressor gene involved in malignancy. A role for phosphoinositide (PI)-specific phospholipase C (PLC) η2, whose gene maps on 1p36.32, was suggested. PI-PLC η2 belongs to a family of enzymes related to the phosphoinositide signalling pathway, which provide an important intracellular signalling system involved in a variety of cell functions such as hormone secretion, neurotransmitter signal transduction, cell growth, membrane trafficking, ion channel activity, regulation of the cytoskeleton, cell cycle control and apoptosis. Expression of PI-PLC η2 occurs after birth and continues throughout the life. Synapse formation occurs during a short period of postnatal development. Thus, it is likely that PI-PLC η2 acts in formation and maintenance of the neuronal network in the brain. The fact that PI-PLC η2, a highly neuron-specific isozyme, is abundantly expressed in the postnatal brain suggests the importance of PI-PLC η2 in formation and maintenance of the neuronal network in the postnatal brain. Further studies are required to verify the possible involvement of PI-PLC η2 mutation/deletion in central nervous tumour tissues presenting abnormalities of the 1p36 chromosomal band.

  10. SIL-TAL1 rearrangement is related with poor outcome: a study from a Chinese institution.

    Directory of Open Access Journals (Sweden)

    Di Wang

    Full Text Available SIL-TAL1 rearrangement is common in T-cell acute lymphoblastic leukemia (T-ALL, however its prognostic implication remains controversial. To investigate the clinical characteristics and outcome of this subtype in Chinese population, we systemically reviewed 62 patients with newly diagnosed T-ALL, including 15 patients with SIL-TAL1 rearrangement. We found that SIL-TAL1(+ T-ALL was characterized by higher white blood cell count (P = 0.029 at diagnosis, predominant cortical T-ALL immunophenotype (P = 0.028 of the leukemic blasts, and a higher prevalence of tumor lysis syndrome (TLS, P<0.001 and disseminated intravascular coagulation (DIC, P<0.001, which led to a higher early mortality (P = 0.011. Compared with SIL-TAL1(- patients, SIL-TAL1(+ patients had shorter relapse free survival (P = 0.007 and overall survival (P = 0.002. Our NOD/SCID xenotransplantation model also demonstrated that SIL-TAL1(+ mice models had earlier disease onset, higher leukemia cell load in peripheral blood and shorter overall survival (P<0.001. Moreover, the SIL-TAL1(+ mice models exerted a tendency of TLS/DIC and seemed vulnerable towards chemotherapy, which further simulated our clinical settings. These data demonstrate that SIL-TAL1 rearrangement identifies a distinct subtype with inferior outcome which could allow for individual therapeutic stratification for T-ALL patients.

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

    Science.gov (United States)

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

    2016-04-01

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

  12. Rearrangement of MICU1 multimers for activation of MCU is solely controlled by cytosolic Ca(2.).

    Science.gov (United States)

    Waldeck-Weiermair, Markus; Malli, Roland; Parichatikanond, Warisara; Gottschalk, Benjamin; Madreiter-Sokolowski, Corina T; Klec, Christiane; Rost, Rene; Graier, Wolfgang F

    2015-10-22

    Mitochondrial Ca(2+) uptake is a vital process that controls distinct cell and organelle functions. Mitochondrial calcium uptake 1 (MICU1) was identified as key regulator of the mitochondrial Ca(2+) uniporter (MCU) that together with the essential MCU regulator (EMRE) forms the mitochondrial Ca(2+) channel. However, mechanisms by which MICU1 controls MCU/EMRE activity to tune mitochondrial Ca(2+) signals remain ambiguous. Here we established a live-cell FRET approach and demonstrate that elevations of cytosolic Ca(2+) rearranges MICU1 multimers with an EC50 of 4.4 μM, resulting in activation of mitochondrial Ca(2+) uptake. MICU1 rearrangement essentially requires the EF-hand motifs and strictly correlates with the shape of cytosolic Ca(2+) rises. We further show that rearrangements of MICU1 multimers were independent of matrix Ca(2+) concentration, mitochondrial membrane potential, and expression levels of MCU and EMRE. Our experiments provide novel details about how MCU/EMRE is regulated by MICU1 and an original approach to investigate MCU/EMRE activation in intact cells.

  13. Infinite-order discrete-variable representation theory of rearrangement scattering

    CERN Document Server

    Choi, N N; Suck-Salk, S H

    1999-01-01

    We recently developed the infinite-order discrete-variable representation (IO-DVR) theory of quantum scattering, which has been proven to yield highly accurate results even for multidimensional rearrangement scattering systems. In this paper we illustrate this theory by considering a one-dimensional reaction path model in which the potential is taken to be an Eckart barrier. In another application, we consider a two-degree-of-freedom model for H + H sub 2 rearrangement collisions. This application is sufficiently complex that it is impractical to calculate the rearrangement scattering matrix by using the previous theory of Eisenberg et al., but with the IO-DVR theory, the problem is made easy. We demonstrate the convergence behavior of the IO-DVR theory with the size of the interaction region and the density of the DVR grid points. Also we find that the set of linear equations involved in this application is efficiently solved via an iterative method which exploits the sparsity of the relevant matrix.

  14. Evolution of Ig- and T-cell receptor gene configuration in a Ph1+ hybrid leukemia patient

    DEFF Research Database (Denmark)

    Jensen, Arne Willy; Hokland, Peter; Kristensen, J S;

    1992-01-01

    the configuration of the Ig heavy and light chain lambda genes remained constant during the whole period of treatment, that of the Ig light chain kappa gene and TCR beta gene displayed extensive rearrangements after initiation of ALL therapy. Since this patient represents a de novo acute leukemia as evaluated...

  15. Screening for subtelomeric rearrangements in 210 patients with unexplained mental retardation using multiplex ligation dependent probe amplification (MLPA).

    NARCIS (Netherlands)

    Koolen, D.A.; Nillesen, W.M.; Versteeg, M.H.; Merkx, G.F.M.; Knoers, N.V.A.M.; Kets, M.; Vermeer, S.; Ravenswaaij-Arts, C.M.A. van; Kovel, C.G.F. de; Brunner, H.G.; Smeets, D.F.C.M.; Vries, L.B.A. de; Sistermans, E.A.

    2004-01-01

    BACKGROUND: Subtelomeric rearrangements contribute to idiopathic mental retardation and human malformations, sometimes as distinct mental retardation syndromes. However, for most subtelomeric defects a characteristic clinical phenotype remains to be elucidated. OBJECTIVE: To screen for submicroscopi

  16. Conventional and fluorescence in situ hybridization analysis of three-way complex BCR-ABL rearrangement in a chronic myeloid leukemia patient

    Directory of Open Access Journals (Sweden)

    Ganguly Bani

    2007-01-01

    Full Text Available Chromosomal analysis was carried out in bone marrow sample of an 11-year-old girl suspected of myeloproliferative disorder. Conventional G-banding study detected a complex three-way translocation involving 7, 9 and 22, which has resulted in the formation of a variant Philadelphia chromosome causing rearrangement of abl and bcr genes in 87% cells. Fluorescence in situ hybridization (FISH confirmed the fusion of bcr-abl oncogene. Thus the bone marrow karyotype was observed as 46,XX (13% / 46,XX,t(7;9;22(q11;q34;q11 (87%. Hyperdiploidy was present in two cells. In this study, both conventional cytogenetic and FISH diagnosis proved to be significant to identify the variant nature of the Philadelphia chromosome and hyperdiploid condition for introduction of a suitable treatment regimen and estimation of life expectancy of the young girl.

  17. The complete mitochondrial genome of the citrus red mite Panonychus citri (Acari: Tetranychidae: high genome rearrangement and extremely truncated tRNAs

    Directory of Open Access Journals (Sweden)

    Dou Wei

    2010-10-01

    either the T- or D-arm, as found in P. ulmi, T. urticae, and other Acariform mites. Conclusions The P. citri mitochondrial gene order is markedly different from those of other chelicerates, but is conserved within the family Tetranychidae indicating that high rearrangements have occurred after Tetranychidae diverged from other Acari. Comparative analyses suggest that the genome size, gene order, gene content, codon usage, and base composition are strongly variable among Acari mitochondrial genomes. While extremely small and unusual tRNA genes seem to be common for Acariform mites, further experimental evidence is needed.

  18. Fusion of short telomeres in human cells is characterized by extensive deletion and microhomology, and can result in complex rearrangements

    OpenAIRE

    Letsolo, Boitelo T.; Rowson, Jan; Baird, Duncan M.

    2009-01-01

    Telomere fusion is an important mutational event that has the potential to lead to large-scale genomic rearrangements of the types frequently observed in cancer. We have developed single-molecule approaches to detect, isolate and characterize the DNA sequence of telomere fusion events in human cells. Using these assays, we have detected complex fusion events that include fusion with interstitial loci adjacent to fragile sites, intra-molecular rearrangements, and fusion events involving the te...

  19. Mechanistic studies of the vapor-phase Beckmann rearrangement on solid catalysts by in situ solid-state NMR spectroscopy

    OpenAIRE

    Marthala, Venkata Ramana Reddy

    2009-01-01

    Epsilon-Caprolactam, the main product of the Beckmann rearrangement of cyclohexanone oxime, is an intermediate in the manufacture of nylon-6. Currently, most of the industrial plants produce epsilon-caprolactam by the Beckmann rearrangement of cyclohexanone oxime using sulphuric acid or oleum as a homogeneous catalyst. This process has two main disadvantages: (i) The production of uneconomical by-product, such as ammonium sulphate, and (ii) the environmentally unfriendly corrosive reaction me...

  20. Duplication and Remolding of tRNA Genes in the Mitochondrial Genome of Reduvius tenebrosus (Hemiptera: Reduviidae)

    OpenAIRE

    Pei Jiang; Hu Li; Fan Song; Yao Cai; Jianyun Wang; Jinpeng Liu; Wanzhi Cai

    2016-01-01

    Most assassin bugs are predators that act as important natural enemies of insect pests. Mitochondrial (mt) genomes of these insects are double-strand circular DNAs that encode 37 genes. In the present study, we explore the duplication and rearrangement of tRNA genes in the mt genome of Reduvius tenebrosus, the first mt genome from the subfamily Reduviinae. The gene order rearranges from CR (control region)-trnI-trnQ-trnM-ND2 to CR-trnQ-trnI2-trnI1-trnM-ND2. We identified 23 tRNA genes, includ...

  1. Molecular pathways: targeting ETS gene fusions in cancer.

    Science.gov (United States)

    Feng, Felix Y; Brenner, J Chad; Hussain, Maha; Chinnaiyan, Arul M

    2014-09-01

    Rearrangements, or gene fusions, involving the ETS family of transcription factors are common driving events in both prostate cancer and Ewing sarcoma. These rearrangements result in pathogenic expression of the ETS genes and trigger activation of transcriptional programs enriched for invasion and other oncogenic features. Although ETS gene fusions represent intriguing therapeutic targets, transcription factors, such as those comprising the ETS family, have been notoriously difficult to target. Recently, preclinical studies have demonstrated an association between ETS gene fusions and components of the DNA damage response pathway, such as PARP1, the catalytic subunit of DNA protein kinase (DNAPK), and histone deactylase 1 (HDAC1), and have suggested that ETS fusions may confer sensitivity to inhibitors of these DNA repair proteins. In this review, we discuss the role of ETS fusions in cancer, the preclinical rationale for targeting ETS fusions with inhibitors of PARP1, DNAPK, and HDAC1, as well as ongoing clinical trials targeting ETS gene fusions.

  2. Transposable element origins of epigenetic gene regulation.

    Science.gov (United States)

    Lisch, Damon; Bennetzen, Jeffrey L

    2011-04-01

    Transposable elements (TEs) are massively abundant and unstable in all plant genomes, but are mostly silent because of epigenetic suppression. Because all known epigenetic pathways act on all TEs, it is likely that the specialized epigenetic regulation of regular host genes (RHGs) was co-opted from this ubiquitous need for the silencing of TEs and viruses. With their internally repetitive and rearranging structures, and the acquisition of fragments of RHGs, the expression of TEs commonly makes antisense RNAs for both TE genes and RHGs. These antisense RNAs, particularly from heterochromatic reservoirs of 'zombie' TEs that are rearranged to form variously internally repetitive structures, may be advantageous because their induction will help rapidly suppress active TEs of the same family. RHG fragments within rapidly rearranging TEs may also provide the raw material for the ongoing generation of miRNA genes. TE gene expression is regulated by both environmental and developmental signals, and insertions can place nearby RHGs under the regulation (both standard and epigenetic) of the TE. The ubiquity of TEs, their frequent preferential association with RHGs, and their ability to be programmed by epigenetic signals all indicate that RGHs have nearly unlimited access to novel regulatory cassettes to assist plant adaptation. PMID:21444239

  3. Analysis of gene expression in resynthesized Brassica napus Allopolyploids using arabidopsis 70mer oligo microarrays.

    Directory of Open Access Journals (Sweden)

    Robert T Gaeta

    Full Text Available BACKGROUND: Studies in resynthesized Brassica napus allopolyploids indicate that homoeologous chromosome exchanges in advanced generations (S(5ratio6 alter gene expression through the loss and doubling of homoeologous genes within the rearrangements. Rearrangements may also indirectly affect global gene expression if homoeologous copies of gene regulators within rearrangements have differential affects on the transcription of genes in networks. METHODOLOGY/PRINCIPAL FINDINGS: We utilized Arabidopsis 70mer oligonucleotide microarrays for exploring gene expression in three resynthesized B. napus lineages at the S(0ratio1 and S(5ratio6 generations as well as their diploid progenitors B. rapa and B. oleracea. Differential gene expression between the progenitors and additive (midparent expression in the allopolyploids were tested. The S(5ratio6 lines differed in the number of genetic rearrangements, allowing us to test if the number of genes displaying nonadditive expression was related to the number of rearrangements. Estimates using per-gene and common variance ANOVA models indicated that 6-15% of 26,107 genes were differentially expressed between the progenitors. Individual allopolyploids showed nonadditive expression for 1.6-32% of all genes. Less than 0.3% of genes displayed nonadditive expression in all S(0ratio1 lines and 0.1-0.2% were nonadditive among all S(5ratio6 lines. Differentially expressed genes in the polyploids were over-represented by genes differential between the progenitors. The total number of differentially expressed genes was correlated with the number of genetic changes in S(5ratio6 lines under the common variance model; however, there was no relationship using a per-gene variance model, and many genes showed nonadditive expression in S(0ratio1 lines. CONCLUSIONS/SIGNIFICANCE: Few genes reproducibly demonstrated nonadditive expression among lineages, suggesting few changes resulted from a general response to polyploidization

  4. Immunoglobulin genes and T-cell receptors as molecular markers in children with acute lymphoblastic leukaemia

    Directory of Open Access Journals (Sweden)

    Lazić Jelena

    2009-01-01

    Full Text Available Introduction. Acute lymphoblastic leukaemia (ALL is a malignant clonal disease, one of the most common malignancies in childhood. Contemporary protocols ensure high remission rate and long term free survival. The ability of molecular genetic methods help to establish submicroscopic classification and minimal residual disease (MRD follow up, in major percent responsible for relapse. Objective. The aim of the study was to detect the frequency of IgH and TCR gene rearrangements and their correlation with clinical parameters. Methods. Forty-one children with ALL were enrolled in the study group, with initial diagnosis of IgH and TCR gene rearrangements by polimerase chain reaction ( PCR. MRD follow-up was performed in induction phase when morphological remission was expected, and after intensive chemiotherapy. Results. In the study group IgH rearrangement was detected in 82.9% of children at the diagnosis, while TCR rearrangement was seen in 56.1%. On induction day 33, clonal IgH rearrangements persisted in 39% and TCR rearrangements in 36.5% of children. Conclusion. Molecular analysis of genetic alterations and their correlation with standard prognostic parameters show the importance of risk stratification revision which leads to new therapy intensification approach. MRD stands out as a precise predictive factor for the relapse of disease.

  5. Improved outcome with hematopoietic stem cell transplantation in a poor prognostic subgroup of infants with mixed-lineage-leukemia (MLL)-rearranged acute lymphoblastic leukemia: results from the Interfant-99 Study

    DEFF Research Database (Denmark)

    Mann, Georg; Attarbaschi, Andishe; Schrappe, Martin;

    2010-01-01

    To define a role for hematopoietic stem cell transplantation (HSCT) in infants with acute lymphoblastic leukemia and rearrangements of the mixed-lineage-leukemia gene (MLL(+)), we compared the outcome of MLL(+) patients from trial Interfant-99 who either received chemotherapy only or HSCT. Of 376...... such high-risk criteria, with 87 achieving CR. In this group, HSCT was associated with a 64% reduction in the risk of failure resulting from relapse or death in CR (hazard ratio = 0.36, 95% confidence interval, 0.15-0.86). In the remaining patients, there was no advantage for HSCT over chemotherapy only...

  6. Further delineation of complex chromosomal rearrangements in fertile male using multicolor banding

    Directory of Open Access Journals (Sweden)

    Weise Anja

    2008-08-01

    Full Text Available Abstract Background Complex chromosomal rearrangements (CCRs are defined as structural chromosomal rearrangements with at least three breakpoints and exchange of genetic material between two or more chromosomes. Complex chromosomal translocations are rarely seen in the general population but the frequency of occurrence is anticipated to be much higher due balanced states with no phenotypic presentation. Here, we report a severely mentally retarded fertile male patient in whom further delineation of CCR involving chromosomes 1, 4 and 2 was carried out by using high resolution multicolor banding (MCB technique. As a FISH based novel chromosome banding approach, high resolution MCB allows for the differentiation of chromosome region specific areas at band and subband levels. Results Cytogenetic studies using high resolution banding of the proband necessitated further delineation of the breakpoints because of their uncertainty: 46,XY,t(1;4;2(p21~31;q31.3;q31. After using high resolution MCB based on microdissection derived region-specific libraries, the exact nature of chromosomal rearrangements for chromosomes 1, 2 and 4 were revealed and these breakpoints were located on 1p31.1, 1q24.3 and 4q31.3 giving rise to a balanced situation. Conclusion Further delineations are certainly required to provide detailed information about the relationship between balanced CCRs and their phenotypes in order to offer proper counseling to the families concerned. Carriers must be investigated with high resolution banding and molecular cytogenetic techniques to determine the exact locations of the breakpoints. High resolution MCB is an alternative and an efficient method to other FISH based chromosome banding techniques and can serve in clarifying the nature of CCR.

  7. A saturated SSR/DArT linkage map of Musa acuminata addressing genome rearrangements among bananas

    Directory of Open Access Journals (Sweden)

    Matsumoto Takashi

    2010-04-01

    Full Text Available Abstract Background The genus Musa is a large species complex which includes cultivars at diploid and triploid levels. These sterile and vegetatively propagated cultivars are based on the A genome from Musa acuminata, exclusively for sweet bananas such as Cavendish, or associated with the B genome (Musa balbisiana in cooking bananas such as Plantain varieties. In M. acuminata cultivars, structural heterozygosity is thought to be one of the main causes of sterility, which is essential for obtaining seedless fruits but hampers breeding. Only partial genetic maps are presently available due to chromosomal rearrangements within the parents of the mapping populations. This causes large segregation distortions inducing pseudo-linkages and difficulties in ordering markers in the linkage groups. The present study aims at producing a saturated linkage map of M. acuminata, taking into account hypotheses on the structural heterozygosity of the parents. Results An F1 progeny of 180 individuals was obtained from a cross between two genetically distant accessions of M. acuminata, 'Borneo' and 'Pisang Lilin' (P. Lilin. Based on the gametic recombination of each parent, two parental maps composed of SSR and DArT markers were established. A significant proportion of the markers (21.7% deviated (p Conclusions We propose a synthetic map with 11 linkage groups containing 489 markers (167 SSRs and 322 DArTs covering 1197 cM. This first saturated map is proposed as a "reference Musa map" for further analyses. We also propose two complete parental maps with interpretations of structural rearrangements localized on the linkage groups. The structural heterozygosity in P. Lilin is hypothesized to result from a duplication likely accompanied by an inversion on another chromosome. This paper also illustrates a methodological approach, transferable to other species, to investigate the mapping of structural rearrangements and determine their consequences on marker

  8. Evolutionary advantage conferred by an eukaryote-to-eukaryote gene transfer event in wine yeasts

    OpenAIRE

    Marsit, Souhir; Mena, Adriana; Bigey, Frederic; Sauvage, Francois Xavier; Couloux, Arnaud; Guy, Julie; Legras, Jean Luc; Barrio, Eladio; Dequin, Sylvie

    2015-01-01

    Although an increasing number of horizontal gene transfers have been reported in eukaryotes, experimental evidence for their adaptive value is lacking. Here, we report the recent transfer of a 158-kb genomic region between Torulaspora microellipsoides and Saccharomyces cerevisiae wine yeasts or closely related strains. This genomic region has undergone several rearrangements in S. cerevisiae strains, including gene loss and gene conversion between two tandemly duplicated FOT genes encoding ol...

  9. Cooperative rearranging region size and free volume in As-Se glasses.

    Science.gov (United States)

    Saiter, A; Saiter, J-M; Golovchak, R; Shpotyuk, M; Shpotyuk, O

    2009-02-18

    Glasses of the As-Se system have been used as model objects of the covalent disordered inorganic polymers to investigate the correlation between the cooperative rearranging region (CRR) size determined at the glass transition temperature and the free volume fraction in the glassy state. The CRR size has been determined using temperature modulated differential scanning calorimetry data according to Donth's approach, while the free volume fraction in the investigated materials has been estimated using positron annihilation lifetime spectroscopy data. The obtained results testify that the appearance of open-volume defects greater than 80 Å(3) leads to a significant decrease in the CRR size. PMID:21817320

  10. Cooperative rearranging region size and free volume in As-Se glasses

    International Nuclear Information System (INIS)

    Glasses of the As-Se system have been used as model objects of the covalent disordered inorganic polymers to investigate the correlation between the cooperative rearranging region (CRR) size determined at the glass transition temperature and the free volume fraction in the glassy state. The CRR size has been determined using temperature modulated differential scanning calorimetry data according to Donth's approach, while the free volume fraction in the investigated materials has been estimated using positron annihilation lifetime spectroscopy data. The obtained results testify that the appearance of open-volume defects greater than 80 A3 leads to a significant decrease in the CRR size.

  11. Toward Singlet-Triplet Bistable Nonalternant Kekulé Hydrocarbons: Azulene-to-Naphthalene Rearrangement.

    Science.gov (United States)

    Das, Soumyajit; Wu, Jishan

    2015-12-01

    Recent developments of open-shell singlet diradicaloids motivated the search for stable singlet-triplet bistable nonalternant polycyclic hydrocarbons. During the synthesis of this type of molecule, such as the dibenzo-cyclohepta[def]fluorene 3, an unexpected azulene-to-naphthalene rearrangement was observed at room temperature, which resulted in new nonalternant hydrocarbons 8a/8b with a closed-shell singlet ground state. These studies provided insight into the unique chemistry of azulene and challenges for the synthesis of singlet-triplet bistable polycyclic hydrocarbons. PMID:26569547

  12. Cooperative rearranging region size and free volume in As-Se glasses.

    Science.gov (United States)

    Saiter, A; Saiter, J-M; Golovchak, R; Shpotyuk, M; Shpotyuk, O

    2009-02-18

    Glasses of the As-Se system have been used as model objects of the covalent disordered inorganic polymers to investigate the correlation between the cooperative rearranging region (CRR) size determined at the glass transition temperature and the free volume fraction in the glassy state. The CRR size has been determined using temperature modulated differential scanning calorimetry data according to Donth's approach, while the free volume fraction in the investigated materials has been estimated using positron annihilation lifetime spectroscopy data. The obtained results testify that the appearance of open-volume defects greater than 80 Å(3) leads to a significant decrease in the CRR size.

  13. Cooperative rearranging region size and free volume in As-Se glasses

    Energy Technology Data Exchange (ETDEWEB)

    Saiter, A; Saiter, J-M [Laboratoire PBM, UMR 6522, LECAP, Institut des Materiaux de Rouen, Universite de Rouen, Faculte des Sciences, Avenue de l' Universite BP 12, 76801 Saint Etienne du Rouvray (France); Golovchak, R; Shpotyuk, M; Shpotyuk, O [Lviv Scientific Research Institute of Materials of SRC ' Carat' , 202, Stryjska street, Lviv, UA-79031 (Ukraine)

    2009-02-18

    Glasses of the As-Se system have been used as model objects of the covalent disordered inorganic polymers to investigate the correlation between the cooperative rearranging region (CRR) size determined at the glass transition temperature and the free volume fraction in the glassy state. The CRR size has been determined using temperature modulated differential scanning calorimetry data according to Donth's approach, while the free volume fraction in the investigated materials has been estimated using positron annihilation lifetime spectroscopy data. The obtained results testify that the appearance of open-volume defects greater than 80 A{sup 3} leads to a significant decrease in the CRR size.

  14. The Combined C—H Functionalization/Cope Rearrangement: Discovery and Applications in Organic Synthesis

    Science.gov (United States)

    Davies, Huw M. L.; Lian, Yajing

    2012-01-01

    Conspectus The development of methods for the stereoselective functionalization of sp3 C–H bonds is a challenging undertaking. This Account describes the scope of the combined C–H functionalization/Cope rearrangement (CHCR), a reaction that occurs between rhodium-stabilized vinylcarbenoids and substrates containing allylic C–H bonds. Computational studies have shown that the CHCR reaction is initiated by a hydride transfer to the carbenoid from an allyl site of the substrate, which is then rapidly followed by C–C bond formation between the developing rhodium-bound allyl anion and the allyl cation. In principle, the reaction can proceed through four distinct orientations of the vinylcarbenoid and the approaching substrate. The early examples of the CHCR reaction were all highly diastereoselective, consistent with a reaction proceeding via a chair transition state with the vinylcarbenoid adopting an s-cis conformation. Recent computational studies have revealed that other transition state orientations are energetically accessible, and these results have guided the development of highly stereoselective CHCR reactions that proceed through a boat transition state with the vinylcarbenoid in an s-cis configuration. The CHCR reaction has broad applications in organic synthesis. In some new protocols, the CHCR reaction acts as a surrogate to some of the classic synthetic strategies in organic chemistry. The CHCR reaction has served as a synthetic equivalent of the Michael reaction, the vinylogous Mukaiyama aldol reaction, the tandem Claisen rearrangement/Cope rearrangement, and the tandem aldol reaction/siloxy-Cope rearrangement. In all of these cases, the products are generated with very high diastereocontrol. With a chiral dirhodium tetracarboxylate catalyst such as Rh2(S-DOSP)4 or Rh2(S-PTAD)4, researchers can achieve very high levels of asymmetric induction. Applications of the CHCR reaction include the effective enantiodifferentiation of racemic

  15. Molecular Rearrangement of an Aza-Scorpiand Macrocycle Induced by pH: A Computational Study

    Directory of Open Access Journals (Sweden)

    Jesus Vicente De Julián-Ortiz

    2016-07-01

    Full Text Available Rearrangements and their control are a hot topic in supramolecular chemistry due to the possibilities that these phenomena open in the design of synthetic receptors and molecular machines. Macrocycle aza-scorpiands constitute an interesting system that can reorganize their spatial structure depending on pH variations or the presence of metal cations. In this study, the relative stabilities of these conformations were predicted computationally by semi-empirical and density functional theory approximations, and the reorganization from closed to open conformations was simulated by using the Monte Carlo multiple minimum method.

  16. Formation of H3+ due to Intramolecular Bond Rearrangement in Doubly Charged Methanol

    Science.gov (United States)

    de, Sankar; Rajput, Jyoti; Roy, A.; Ghosh, P. N.; Safvan, C. P.

    2006-11-01

    We report the formation of H3+ by proton coagulation in methanol under the impact of low energy Ar8+ projectiles. Our time-of-flight coincidence measurements with CH3OD establish that the H3+ formation arises from intramolecular bond rearrangement of the methyl group. We have performed ab initio quantum chemical calculations that show the preferred pathway for C-H3 bond cleavage. Fragmentation of organic molecules like methanol under impact of highly charged ions is suggested as an alternative mechanism of H3+ formation in outer space.

  17. Photochemical and Beckmann rearrangement of (Z-cholest-4-en-6-one oxime

    Directory of Open Access Journals (Sweden)

    VLADIMIR D. PAVLOVIC

    2004-06-01

    Full Text Available Beckmann rearrangement of (Z-cholest-4-en-6-one oxime (4 (prepared in 4 steps starting from cholest-5-en-3b-ol (1 with thionyl chloride in dioxane solution afforded an enamide-type lactam, i.e., 7-aza-B-homocholest-4-en-6-one (6 as a single product. Photoreaction of the same compound in methanol or benzene-acetic acid solution gave a mixture of products, with the formation of the parent ketone 3 and the occurrence of Z/E isomerization, while the lactam 6 was obtained only when the reaction was performed in methanol and then in very low yield (7 %.

  18. Sphaerococcenol A: a new rearranged bromo-diterpene from the red alga Sphaerococcus coronopifolius

    Energy Technology Data Exchange (ETDEWEB)

    Fenical, W. (Scripps Inst. of Oceanography, La Jolla, CA); Finer, J.; Clardy, J.

    1976-01-01

    Biosynthesis involving bromination mechanisms is now recognized as a characteristic of at least nine families of the red seaweeds (Rhodophyta). While bromine-containing diterpenes are not common among these algae, examples of two ring systems, concinndiol and iriediol, are elaborated only by Laurencia species. The structure of a new bromo-diterpene obtained from extracts of the red seaweed Sphaerococcus coronopifolius is reported. This metabolite appears to result from a methyl migration of a tail to tail diterpene precursor or from more substantial molecular rearrangements.

  19. Development of advanced zeolite catalysts for the vapor phase Beckmann rearrangement of cyclohexanone oxime

    Science.gov (United States)

    Dai, Lian-Xin; Iwaki, Yoshihide; Koyama, Katsuyuki; Tatsumi, Takashi

    1997-11-01

    The vapor phase Beckmann rearrangement of cyclohexanone oxime to ɛ-caprolactam catalyzed by various zeolites was studied. The catalytic performance was greatly affected by both the zeolite structure and diluent solvent. When 1-hexanol was used in place of benzene, the catalytic performance of all catalysts except silicalite-1 was greatly improved. In particular, the selectivity and stability of H-LTL and H-OFF-ERI zeolites remarkably increased; both catalysts exhibited ca. 100% oxime conversion and ɛ-caprolactam selectivity of >95% for 6 h.

  20. 穿刺活检前列腺癌ERG基因重排分析%ERG rearrangement prevalence in Chinese prostatic carcinoma biopsy cohort

    Institute of Scientific and Technical Information of China (English)

    肖立; 殷于磊; 陈燕; 卢晨; 余波

    2015-01-01

    Purpose To study the prevalence and feature of EGR gene rearrangement in prostatic carcinoma. Methods 242 consecu-tive core biopsies of prostatic carcinoma were evaluated. All biopsy specimens contained 6-14 cores from left and right sides separately delivered. The patient age ranged 58 to 91 years, and PSA value 5 ng/ml to more than 5 000 ng/ml. Immunohistochemistry ( IHC) for ERG protein overexpression and fluorescent in situ hybridization ( FISH) for ERG gene rearrangement were performed. Results 42 cases were detected positive for ERG by IHC ( positive rate 17. 4%) , and positive for ERG rearrangement by FISH either, with 19 ca-ses showing fusion through deletion and 23 through insertion, while no negative cases by IHC demonstrated positive by FISH. 5 cases revealed positive and negative staining in different carcinoma foci of ERG. No ERG positive staining and rearrangement were found in adjacent benign glands. Of positive cases, 12 cases were graded as Gleason score 6, 23 Gleason score 7, and 7 Gleason score 8 or more. Positive rate was 19. 6% in the group of PSA value less than 100 ng/ml, and 10% of more than 100 ng/ml, whereas 17. 2% in the group of clinical T3 stage or less, and 19% of clinical T4 and lymph node or remote metastasis. ERG rearrangement was associated with lower Gleason score, but not with PSA value, clinical stage and progression using theχ2 test analysis. Conclusions IHC is relia-ble for detection ERG rearrangement and helpful for interpretation of prostatic carcinoma. Multiple foci are common in prostatic carcino-ma. There is no significance between ERG rearrangement and disease prognosis.%目的:探讨ERG基因重排在前列腺癌中的发生率及特征。方法收集前列腺癌连续穿刺标本242例,均为6~14针,左、右侧不同部位分瓶送检,年龄58~91岁,PSA水平5~5000 ng/ml,免疫组化法检测ERG蛋白表达,荧光原位杂交( fluores-cent in situ hybridization, FISH)技术检测ERG基因重排