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1
TELLO, CAJIAO JOHN JAMES. "Biophysical modelling of radiation-induced chromosome aberrations." Doctoral thesis, Università degli studi di Pavia, 2019. http://hdl.handle.net/11571/1291026.
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Anderson, Rhona M. "Complex chromosome aberrations induced by densely ionising radiation." Thesis, Brunel University, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.412322.
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Huang, H. E. "Chromosome aberrations targeting the NRG1 gene in cancer." Thesis, University of Cambridge, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.604700.
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Thirty-four breast and nine pancreatic cancer cell lines were surveyed for alterations of the NRG1 gene by fluorescence in situ hybridization (FISH). A recent chromosome translocation breakpoint that targets the NRG1 gene was found in five breast and two pancreatic lines. High-resolution mapping by two-colour FISH showed that the breakpoints were clustered in a 1.1 Mb interval within NRG1. RT-PCR showed an extensive complexity of NRG1 transcripts in the translocation-positive lines, suggesting that expression of the ligand is a consequence of these structural arrangements. This study was extended to primary tumour material to confirm the presence and prevalence of NRG1 translocation in uncultured cancer cells. I designed a FISH strategy (using a custom FISH probe-the Neuprobe), which was used in a high-throughput manner on archival paraffin embedded material in the form of tissue microarrays (TMAs).A survey of 339 primary breast carcinomas identified a disruption targeting NRG1 in approximately 6% of all cases examined. The common abnormality seen was a deletion in the 5’ end of the gene, often accompanied by amplification of the 3’ end. Genomic alteration of NRG1 was associated with ectopic expression of NRG1 α and β isoforms. Fine mapping confirmed that these breakpoints cluster within the same region seen in cell lines. These results were independently validated by array-based CGH, using a custom made array with overlapping BACS spanning 8p12. NRG1 translocation was associated with high-grade tumours, low HER2 expression, and high expression levels of FGFR1, TACC (both in close genomic proximity to NRG1). A further survey of 242 primary ovarian tumours identified the same abnormality in 10% of tumours.
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Crouch, Joelle H. "Chromosome aberrations in field strains of Blattella germanica." Thesis, Virginia Tech, 1993. http://hdl.handle.net/10919/42132.
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Koen, Liezl. "Chromosomal aberrations in the Xhosa schizophrenia population." Thesis, Stellenbosch : Stellenbosch University, 2008. http://hdl.handle.net/10019.1/1189.
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Thesis (PhD (Psychiatry))--Stellenbosch University, 2008.BACKGROUND: Schizophrenia is a heterogeneous illness resulting from complex gene-environment interplay. The majority of molecular genetic work done has involved Caucasian populations, with studies in these and Asian populations showing 2-32% of sufferers to have chromosomal aberrations. So far the discovery of a specific susceptibility mechanism or gene still eludes us, but the use of endophenotypes is advocated as a useful tool in this search. No cytogenetic studies of this nature have been reported in any African schizophrenia population. AIM: The aim of the study was to combine genotypic and phenotypic data, collected in a homogenous population in a structured manner, with the hope of characterising an endophenotype that could be used for more accurate identification of individuals with possible chromosomal abnormalities. METHODOLOGY: A structured clinical interview was conducted on 112 Xhosa schizophrenia patients. (Diagnostic Interview for Genetic Studies, including Schedules for the Assessment of Negative and Positive Symptoms.) Blood samples (karyotyping and/or FISH analysis) as well as urine samples (drug screening) were obtained and nine head and facial measurements were performed. Descriptive statistics were compiled with reference to demographic, clinical and morphological variables. Comparisons between mean differences for these variables were made.
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AUFFRET, PASCALE. "Malformations et tube neural et aberrations chromosomiques." Rennes 1, 1993. http://www.theses.fr/1993REN1M078.
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Anderlid, Britt-Marie. "Cryptic chromosome abnormalities in idiopathic mental retardation /." Stockholm : [Karolinska institutets bibl.], 2001. http://diss.kib.ki.se/2001/91-7349-097-0/.
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Calero, Moreno Teresa. "Genetic changes in childhood acute lymphoblastic leukaemia and other lymphoid malignancies /." Stockholm, 2001. http://diss.kib.ki.se/2001/91-628-4625-6/.
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Koen, Liezl. "Chromosomal aberrations in the Xhosa shizophrenia population /." Link to the online version, 2008. http://hdl.handle.net/10019/1697.
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Fujioka, Kaoru. "Centrosome aberrations and tumor development /." Stockholm, 2003. http://diss.kib.ki.se/2003/91-7349-627-8/.
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Chiu, Kam-hung, and 趙錦鴻. "Genetic aberrations in chronic lymphocytic leukaemia as prognostic markers." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2008. http://hub.hku.hk/bib/B41290781.
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Chiu, Kam-hung. "Genetic aberrations in chronic lymphocytic leukaemia as prognostic markers." Click to view the E-thesis via HKUTO, 2008. http://sunzi.lib.hku.hk/hkuto/record/B41290781.
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Darai-Ramqvist, Eva. "Involvement of evolutionarily plastic regions in cancer associated CHR3 aberrations /." Stockholm, 2007. http://diss.kib.ki.se/2007/978-91-7357-192-0/.
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Herrington, Charles Simon. "In situ analysis of human papillomaviruses and chromosome aberrations in cervical neoplasia." Thesis, University of Oxford, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.279806.
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Pirzio, Livia. "Formation of radiation induced chromosome aberrations : involvement of telomeric sequences and telomerase." Paris 11, 2004. http://www.theses.fr/2004PA11TO31.
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Bruyère, Hélène. "Chromosome 15 en anneau : syndrome clinique, détermination des points de cassure et revue de la littérature : à propos d'un cas." Saint-Etienne, 1995. http://www.theses.fr/1995STET6410.
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Moquet, Jayne Elizabeth. "Studies of genotoxicity and apoptosis using human lymphocytes or murine neuroblastoma cells exposed in vitro to radiofrequency fields characteristic of mobile phones." Thesis, Brunel University, 2009. http://bura.brunel.ac.uk/handle/2438/4378.
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The aim of the study was to investigate whether non-thermal levels of radiofrequency (RF) fields, characteristic of some mobile phones, might be directly genotoxic when applied in vitro to unstimulated G0 or stimulated human lymphocytes. Also, the study aimed to investigate the possibility that RF fields might act epipigenetically when combined with x-rays, by modifying their effect when applied in vitro to G0 lymphocytes. In addition, the possibility of RF fields inducing apoptosis in murine neuroblastoma (N2a) cells was also examined. G0 lymphocytes from 4 donors were exposed for a total of 24 h to a continuous or an intermittent RF signal. The signals were 935 MHz GSM (Global System for Mobile Communication) Basic, 1800 MHz GSM Basic, 935 MHz continuous wave (CW) carrier frequency, and 935 MHz GSM Talk. Stimulated lymphocytes were exposed for a total of 48 h to intermittent 1800 MHz RF signals that were GSM Basic or the carrier frequency only. The RF fields used for the 24 h exposure of N2a cells were all at 935 MHz and consisted of GSM Basic, GSM Talk and a CW signal. The chosen Specific energy Absorption values of the signals were either 1 or 2 W/kg. These values are near the upper limit of actual energy absorbed in localised tissue by a person from some mobile phones. The field was applied to G0 human lymphocytes either alone or combined with an exposure to 1 Gy x-rays given immediately before or after the RF field. A dose of 4 Gy x-rays was used as a positive control for apoptosis induction in N2a cells and in the study with stimulated lymphocytes no x-rays were used. The lymphocytes were assayed by several standard methods to demonstrate genotoxicity. Unstable chromosome aberrations (stimulated lymphocytes and those exposed in G0), sister chromatid exchanges (SCE) and cytokinesis blocked micronuclei (MN) (lymphocytes exposed in G0). In addition the SCE and MN assays allowed nuclear division indices (NDI) to be calculated as NDI defines the cell cycle progression of lymphocytes after PHA stimulation and how this might be affected by RF exposure. N2a cells were assessed by fluorescence microscopy for levels of apoptosis at a number of time points post RF field or x-ray exposure, between 0 and 48 h. Three independent assays that detect different stages of the apoptotic pathway were used, the Annexin V binding, caspase activation and in situ end labelling. By comparison with appropriate sham exposed samples no effect of RF fields alone could be found in G0 or PHA stimulated lymphocytes exposed in vitro. Also, RF fields did not modify any measured effects of x-rays either given before or after RF exposure. No statistically significant difference in apoptosis levels were observed between RF exposed and sham exposed N2a cells in either a proliferating or differentiated state for any assay at any time point post exposure.
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Launonen, V. (Virpi). "Genetic aberrations and their clinical significance in breast and ovarian cancer." Doctoral thesis, University of Oulu, 1999. http://urn.fi/urn:isbn:9514251946.
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Abstract
In tumourigenesis, genetic alterations accumulate in the genes responsible for cell growth, proliferation and DNA repair: proto-oncogenes, tumour suppressor and DNA repair genes. Inactivation of tumour suppressor gene function is commonly recognised as a deletion of one of the two alleles; LOH, loss of heterozygosity. In the present study, LOH of several chromosomal regions was studied in both breast and ovarian cancer.
LOH for chromosome region 11q was examined in a large breast cancer consortium cohort (N = 988) and in a Finnish ovarian cancer cohort (N = 78), and the clinical significance of these alterations was evaluated. In breast cancer, LOH of the studied markers at 11q23.1, harbouring approximately 2 Mb of DNA, was seen to be associated with shortened cancer-specific survival. Two candidate genes, ATM (the ataxia telangiectasia disorder gene) and DDX10 (a putative RNA helicase gene) map to this chromosomal region.
In ovarian cancer, LOH at 11q23.1–q24 was assigned mainly to two chromosomal regions, A and B, which are proximal and distal to 11q23.2–q23.3, respectively. Only the distal B region was seen to be associated with an aggressive disease course. Therefore, it appears that inactivation of the ATM or DDX10 genes is not crucial for determining the outcome of ovarian cancer. The CHK1 gene at 11q24, encoding a protein kinase required for DNA damage checkpoint function, is a putative target gene at the B region. On the basis of the present results, the main TSG in the studied region involved in the progression of breast cancer maps to 11q23.1 and the corresponding gene for ovarian cancer more distally to 11q23.3-q24.
In addition, LOH at 3p, 6q, 8p, 11p, 16q and 17p was examined and their role in the genetic evolution of ovarian cancer was evaluated. Of the studied chromosomal regions, LOH at 17p appeared to be an early event and LOH at 16q24.3, 11q23.3/q24 and 11p appear to occur later in the progression of ovarian cancer.
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Hornby, Ann Elizabeth. "Detection of a mutation in a human LCAT gene." Thesis, University of British Columbia, 1988. http://hdl.handle.net/2429/27958.
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LCAT deficiency is a rare autosomal recessive disease characterized by low levels of plasma HDL and an inability of the enzyme lecithin:cholesterol acyltransferase (LCAT) to esterify cholesterol. An understanding of the structure and function of the LCAT protein will add significantly to the understanding of reverse cholesterol transport. This understanding can be gained, in part, by studying different mutations within the LCAT gene and their resultant phenotypes. Recombinant DNA technology has been used to determine the nature of a mutation in an LCAT gene of a previously described homozygote with this disorder. Southern blot analysis determined there were no major rearrangements in the genomic DNA at the LCAT locus. An attempt was made to follow segregation of the mutant alleles in three generations of a large pedigree by linkage analysis. There are known polymorphisms at the haptoglobin (Hp) locus, which is linked to LCAT on the long arm of chromosome 16, and in the adenosine phosphoribotransferase (APRT) and choesterol ester transfer protein (CETP) loci which are also on the long arm of chromosome 16, but have not been shown linked to LCAT. The information gained was uninformative in this pedigree. An extensive restriction fragment length polymorphism (RFLP) search in the immediate vicinity of the LCAT gene did not reveal any polymorphic sites. 2.4 kb of the ⋋ phage clone SF1020, obtained from one of the homozygotes, containing exons 1-5 plus 0.5 kb of DNA 5¹ to the LCAT gene, but not exon 6, was subcloned into M13 and sequenced. A cytosine to thymidine (C->T) transition was discovered in exon 4. This would result in a substitution of tryptophan for arginine at amino acid 135. The amino acid arginine is positively charged and resides in one of the most highly charged segments along the amino acid chain of the LCAT protein indicating that this region is likely involved in protein folding. Tryptophan, on the other hand is the most hydrophobic of the amino acids and would, therefore, severely disrupt the interaction of charged amino acids in that region, preventing normal folding of the LCAT protein.Medicine, Faculty of
Medical Genetics, Department of
Graduate
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Dennis, Thomas R. "The significance of chromosomal translocation breakpoints in adult solid tumors : a molecular cytogenetic study of chromosome 3 rearrangements in small cell carcinoma of the lung /." abstract and full text PDF (UNR users only), 1999. http://0-gateway.proquest.com.innopac.library.unr.edu/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:9961140.
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Ramos, Maria Emilia Santos Pereira. "Biomonitoramento genÃtico de indivÃduos expostos ocupacionalmente a pesticidas no povoado Vila Bessa, municÃpio de ConceiÃÃo do JacuÃpe, Bahia." Universidade Federal do CearÃ, 2009. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=4059.
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nÃo hÃO elevado consumo de pesticidas no Brasil e no mundo tem levado grupos de pesquisadores a relacionar essa exposiÃÃo a possÃveis danos genÃticos e agravos a saÃde do trabalhador rural. Estudos revelam que o cÃncer à considerado doenÃa genÃtica, vez que resulta do acÃmulo de mutaÃÃes em genes comprometidos com o controle da proliferaÃÃo e da diferenciaÃÃo celular ou de mutaÃÃes em genes envolvidos com os mecanismos de reparo do DNA. O objetivo dessa estudo foi realizar um biomonitoramento genÃtico em indivÃduos expostos ocupacionalmente a pesticidas avaliando a ocorrÃncias de danos cromossÃmicos, atravÃs do teste do MicronÃcleo em cÃlulas esfoliadas da mucosa bucal, teste Cometa e teste de AberraÃÃes CromossÃmicas em linfÃcitos de sangue perifÃrico. Como tambÃm alteraÃÃes hematolÃgicas e hepÃticas. A populaÃÃo estudada incluiu 32 agricultores moradores do povoado Vila Bessa, ConceiÃÃo do JacuÃpe, Bahia, expostos ocupacionalmente a pesticidas e 30 indivÃduos controle, sem historia de exposiÃÃo a pesticidas. O material para anÃlise do teste do micronÃcleo foi coletado por raspagem da mucosa bucal com escova cytobrush, confeccionado um esfregaÃo e posteriormente fixado em soluÃÃo de metanol/Ãcido acÃtico (3:1) e corados pelo mÃtodo FeÃlgen/Fast Green, as lÃminas foram analisadas em teste cego sob microscopia Ãptica em um mÃnimo de 1000 cÃlulas/indivÃduo. Para realizaÃÃo do teste Cometa e de AberraÃÃes, cromossÃmicas e das alteraÃÃes hematolÃgicas e hepÃticas foram coletadas 10 mL de sangue perifÃrico. O teste Cometa foi executado de acordo com a metodologia descrita por por Singh et al. (1988), foram contados 100 cometas por lÃmina e classificados, por anÃlise visual, dentre cinco categorias de danos (0, 1, 2, 3 e 4), e calculado o Ãndice e a FreqÃÃncia de dano. O teste de AberraÃÃes CromossÃmicas foi realizada atravÃs de culturas de linfÃcitos e obtenÃÃo de metÃfases pela interrupÃÃo da citocinese das cÃlulas. Foram analisados o hemograma, e as transaminases TGO, TGP E GGT que foram processados pelo laboratÃrio de anÃlise bioquÃmica de Escola Bahiana de Medicina e SaÃde PÃblica. NÃo houve diferenÃa significativa na ocorrÃncia de micronÃcleos entre os grupos avaliados (p = 0,163), mas alteraÃÃes nucleares indicativos de apoptose e necrose foram encontradas significantemente no grupo exposto a pesticidas (p = 0,001), indicando que uma maior injÃria celular do que simplesmente uma resposta a diferenciaÃÃo e maturaÃÃo do epitÃlio. AberraÃÃes CromossÃmicas numÃricas (3,3%) foi encontrada significantivamente para o grupo exposto (p = 0,001), foram encontrados danos ao DNA avaliados pelo teste Cometa no escore 1 (p< 0.001) no grupo exposto; alÃm do Ãndice de Dano cromossÃmico com mÃdia  SEM 4.032  0.3336 para o grupo controle e mÃdia  SEM 41.05  3.227 para o grupo exposto a pesticida (p<0,0001); e FreqÃÃncia de Dano: mÃdia  SEM grupo controle 4.081  0.3667 e mÃdia  SEM grupo exposto a pesticida 38.44  2.664, com diferenÃas significativas para o grupo exposto (p<0,0001). Os indivÃduos pesquisados estÃo expostos ao glifosato e ao paration-metÃlico, ambos tÃxicos para o organismo humano, e apresentavam-se anÃmicos (p=0,004) e com leucopenia (p < 0,001), porÃm sem alteraÃÃes nas avaliaÃÃes hepÃticas. ConcluÃmos que esses indivÃduos estÃo expostos a agentes potencialmente genotÃxicos, alÃm de apresentarem alteraÃÃes hematolÃgicas, e que a persistÃncia desse contato com os pesticidas poderà levar a desencadeamento dos fenÃmenos envolvidos na iniciaÃÃo e promoÃÃo do cÃncer.
The high consumption of pesticides in Brazil and all over the world have lead researches to relate this exposition to possible genetic and health damages in rural workers. Studies reveal that cancer is considered a genetic disease, once it results of the mutation accrual in genes involved with control of proliferation and cellular differentiation or mutations in genes involved with the DNA repair. The aim of this study was realize a genetic biomonitoring in individuals occupationally exposed to pesticides evaluating the occurrence of chromosomal damages, by the Micronucleus assay in exfoliated cells of buccal mucosa, Comet assay and Chromosome Aberration assay in peripheral blood lymphocytes. Hematologic and hepatic alterations were also evaluated. The studied population included 32 agriculturists living in the village of Vila Bessa, ConceiÃÃo do JacuÃpe, Bahia, occupationally exposed to pesticides, and 30 control individuals, with no history of pesticides exposition. For the micronucleus assay, the material was collected by scaling buccal mucosa with a cytobrush, the smear was made and then fixed in methanol/acetic acid solution (3:1) and colored by FeÃlgen/Fast Green Method, slides were analyzed in blind test by optic microscopy in a minimum of 1000 cells/individual. To realize the assay of Comet and Aberration, Chromosomal and hematologic and hepatic alterations, were collected 10 mL of peripheral blood. Comet test was made according the methodology described by Singh et al. (1988), were counted 100 comet by slides and classified, by visual analyses, into five categories of damages (0, 1, 2, 3 e 4), and then calculated the index and frequency of damage. Chromosome Aberration test was realized with a lymphocytes culture and obtaining of metaphases by interrupting the cells cytokinesis. The hemogram and the transaminases TGO, TGP and GGT were analyzed; those were processed by the biochemical analyses laboratory of Escola Bahiana de Medicina e SaÃde PÃblica. That wasnÂt statistical difference in the occurrence of micronucleus among the evaluated groups (p = 0.163), but nuclear alterations, indicative of apoptosis and necrosis, were significantly found in the pesticide exposed group (p = 0.001), indicating a major cellular injury than a simple answer to epitheliumÂs differentiation and maturation. Numeric Chromosome Aberrations (3.3%) were significantly found in the exposed group (p = 0.001), were found DNA damages evaluated by the Comet assay in score 1 (p<0.001) in the exposed group; as also index of chromosomal damage with media  SEM 4.032  0.3336 to the control group and media  41.05  3.227 to the pesticide exposed group (p<0.0001); and frequency of damage: media  SEM control group 4.081  0.3667 and media  SEM pesticide exposed group 38.44  2.664, with significant differences in the exposed group (p<0.0001). The studied individuals are exposed to glifosate and methyl parathion, both toxic to the human organism, and were anemics (p=0.004) and with leukopenia (p<0.001), however with no alterations in hepatic evaluations. We conclude that these individuals are exposed to potentially genotoxic agents, besides present hematologic alterations, and that the persistence of this contact with the pesticides can trigger to phenomenonâs involved with cancer initiation and promotion.
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Maziviero, Guilherme Thiago. "Avaliação do potencial citotóxico, genotóxico e mutagênico de esgoto por meio dos sistemas-teste Allium cepa e Tradescantia pallida /." Rio Claro : [s.n.], 2011. http://hdl.handle.net/11449/87700.
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Orientador: Carmem Silvia Fontanetti ChristofolettiBanca: Tatiana da Silva Souza
Banca: Ana Cristina Mielli
Resumo: O lodo de esgoto pode conter substâncias tóxicas, estar contaminado com metais pesados e até mesmo por compostos químicos persistentes, sendo assim, a disposição inadequada desse resíduo pode fazer tais poluentes retornarem ao ambiente e, eventualmente, entrar na cadeia alimentar, caso sejam absorvidos pelas plantas. O conhecimento dos agentes químicos presentes no lodo permite avaliar o risco de contaminação alimentar e ambiental decorrente da utilização de lodos como fertilizantes agrícolas, também chamados de biossólidos. Logo, o presente estudo teve por objetivo avaliar o potencial genotóxico, citotóxico e mutagênico do lodo gerado por uma Estação de Tratamento de Esgoto (ETE), por meio dos sistemas-teste Allium cepa e Tradescantia pallida. As coletas foram realizadas em abril de 2009 e maio de 2010 e os organismos foram expostos ao lodo bruto e seu solubilizado. Quando comparados os resultados obtidos nos bioensaios com as análises físico-químicas, não é possível estabelecer relação de causa e efeito com nenhum composto em específico, uma vez que todos os parâmetros avaliados se encontram dentro dos limites estabelecidos pela Resolução CONAMA 375; no entanto, em ambos os organismos, o lodo apresentou-se genotóxico e mutagênico, alertando sobre a necessidade de cuidado na disponibilização deste tipo de resíduo em solos. Dessa forma é possível concluir que os ensaios de toxicidade genética são capazes de identificar os efeitos diretos do lodo de esgoto e poderiam ser contemplados pela legislação como ferramenta complementar à bateria de testes já estabelecida devido à simplicidade dos testes e custo relativamente reduzido. O trabalho traz ainda uma revisão de literatura sobre a utilização da espécie Tradescantia, suas bases e aplicações das técnicas do pêlo estaminal (Trad-SHM) e teste o do micronúcleo (Trad- MCN), apontando suas... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: Sewage sludge can contain toxic substances, may be contaminated with heavy metals and persistent chemicals, so the improper disposal of this waste can return such pollutants to the environment and possibly return to the food chain if absorbed by plants. The knowledge of chemical agents present in the sludge can assess the risk of food contamination and environmental arising from the use of sludge as agricultural fertilizer, also called biosolids. Therefore, this study aimed to evaluate the potential genotoxic, cytotoxic and mutagenic of sludge generated from a Wastewater Treatment Plant (WTP) by the Allium cepa and Tradescantia pallida tests-systems. Samples were collected in April 2009 and May 2010 and the organisms were exposed to raw sludge and its solublilizated samples. Comparing the results obtained in bioassays with the physico-chemical properties, its cannot establish cause and effect relationship with any compound in particular, since all parameters are within limits set by CONAMA Resolution 375, however, in both organisms, the sludge showed genotoxic and mutagenic, and warns about caution in providing this type of waste in soils. Thus, we conclude that the genetic toxicity tests are able to identify the direct effects of sewage sludge and could be provided by the law as a complementary tool to the battery of tests previously established, due to the simplicity of the tests and relatively low cost. The work also contains a review on the use of Tradescantia species, their bases and applications of the techniques of stamen hair (Trad-SHM) and the micronucleus test (Trad-MCN), pointing out its advantages as a tool for monitoring of environmental health
Mestre
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Grunwald, Monique. "Détection des anomalies chromosomiques par cytométrie en flux et localisation des points de translocation." Paris 6, 1986. http://www.theses.fr/1986PA066487.
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Schoumans, Jacqueline. "Gene dose imbalances in children with mental retardation /." Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-175-X/.
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Maziviero, Guilherme Thiago [UNESP]. "Avaliação do potencial citotóxico, genotóxico e mutagênico de esgoto por meio dos sistemas-teste Allium cepa e Tradescantia pallida." Universidade Estadual Paulista (UNESP), 2011. http://hdl.handle.net/11449/87700.
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O lodo de esgoto pode conter substâncias tóxicas, estar contaminado com metais pesados e até mesmo por compostos químicos persistentes, sendo assim, a disposição inadequada desse resíduo pode fazer tais poluentes retornarem ao ambiente e, eventualmente, entrar na cadeia alimentar, caso sejam absorvidos pelas plantas. O conhecimento dos agentes químicos presentes no lodo permite avaliar o risco de contaminação alimentar e ambiental decorrente da utilização de lodos como fertilizantes agrícolas, também chamados de biossólidos. Logo, o presente estudo teve por objetivo avaliar o potencial genotóxico, citotóxico e mutagênico do lodo gerado por uma Estação de Tratamento de Esgoto (ETE), por meio dos sistemas-teste Allium cepa e Tradescantia pallida. As coletas foram realizadas em abril de 2009 e maio de 2010 e os organismos foram expostos ao lodo bruto e seu solubilizado. Quando comparados os resultados obtidos nos bioensaios com as análises físico-químicas, não é possível estabelecer relação de causa e efeito com nenhum composto em específico, uma vez que todos os parâmetros avaliados se encontram dentro dos limites estabelecidos pela Resolução CONAMA 375; no entanto, em ambos os organismos, o lodo apresentou-se genotóxico e mutagênico, alertando sobre a necessidade de cuidado na disponibilização deste tipo de resíduo em solos. Dessa forma é possível concluir que os ensaios de toxicidade genética são capazes de identificar os efeitos diretos do lodo de esgoto e poderiam ser contemplados pela legislação como ferramenta complementar à bateria de testes já estabelecida devido à simplicidade dos testes e custo relativamente reduzido. O trabalho traz ainda uma revisão de literatura sobre a utilização da espécie Tradescantia, suas bases e aplicações das técnicas do pêlo estaminal (Trad-SHM) e teste o do micronúcleo (Trad- MCN), apontando suas...
Sewage sludge can contain toxic substances, may be contaminated with heavy metals and persistent chemicals, so the improper disposal of this waste can return such pollutants to the environment and possibly return to the food chain if absorbed by plants. The knowledge of chemical agents present in the sludge can assess the risk of food contamination and environmental arising from the use of sludge as agricultural fertilizer, also called biosolids. Therefore, this study aimed to evaluate the potential genotoxic, cytotoxic and mutagenic of sludge generated from a Wastewater Treatment Plant (WTP) by the Allium cepa and Tradescantia pallida tests-systems. Samples were collected in April 2009 and May 2010 and the organisms were exposed to raw sludge and its solublilizated samples. Comparing the results obtained in bioassays with the physico-chemical properties, its cannot establish cause and effect relationship with any compound in particular, since all parameters are within limits set by CONAMA Resolution 375, however, in both organisms, the sludge showed genotoxic and mutagenic, and warns about caution in providing this type of waste in soils. Thus, we conclude that the genetic toxicity tests are able to identify the direct effects of sewage sludge and could be provided by the law as a complementary tool to the battery of tests previously established, due to the simplicity of the tests and relatively low cost. The work also contains a review on the use of Tradescantia species, their bases and applications of the techniques of stamen hair (Trad-SHM) and the micronucleus test (Trad-MCN), pointing out its advantages as a tool for monitoring of environmental health
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Riond, Joëlle. "Benzodiazepines peripheriques." Lyon, INSA, 1990. http://www.theses.fr/1990ISAL0094.
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Les benzodiazépines sont sédatives, anxiolytiques et anti-convulsantes. Leurs s'exercent par l'intermédiaire de récepteurs dans le système nerveux central. Cependant, certaines benzodiazépines se fixent aussi sur un récepteur pharmacologiquement distinct (BPBS), dans les organes périphériques. Celui-ci semble être impliqué dans l'immuno-modulation : nous avons observé un effet des benzodiazépines périphériques sur la prolifération lymphocytaire in vitro. Afin de caractériser le récepteur de ces ligands, nous l'avons purifié à partir de la l ignée cellulaire CHO (hamster), puis clivé, pour en déterminer partiellement la séquence. Un antisérum, obtenu par immunisation avec des peptides synthétiques ana) logues, a été utilisé pour étudier l'homologie entre le BPBS de CHO et celui de la lignée monocytaire humaine U937. A partir des séquences peptidiques du BPBS de CHO quatre sondes d'oligo-nucléotides ont été synthétisés pour isoler l'ADNc d'une banque U937. La région codante séquencée correspond à une protéine de 169 acides présentant plusieurs domaines trans-membranaires potentiels. Enfin, en utilisant l'ADNc isolé comme sonde, nous avons localisé le gène BPBS dans la bande 22q 13. 3 du génome humain[Benzodiazepines are sedative, anxiolytic and anticonvulsant. They exert their effects through receptors in the central nervous system. However, some benzodiazepines also bind to a pharmacologically different receptor (BPBS) in peripheral organs. This one could be involved in immuno-modulation: we observed an effect of peripheral benzodiazepines on lymphocyte proliferation in vitro. To further characterize the receptor of these ligands, we purified it from the CHO cell line (hamster) and we cleaved it to determine a partial sequence. An antiserum directed against synthetic analogous peptides was used to study the homology cell line U937. Using the CHO BPBS peptide sequence, four oligonucleotide probes were synthesised to isolate the BPBS cDNA from a U937 library. The sequenced coding region corresponds to a 169 amino-acid protein with several potential trans-membrane domains. Finally, using the cDNA of the human BPBS as a probe, the BPBS gene was localized in the 22q 13. 3 band of the human genome. ]
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Kuo, Michael Jeo-Ming. "Aberrations of chromosome arms 5q and 8p in squamous cell carcinomas of the head and neck." Thesis, University of Birmingham, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.340558.
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Bhatt, Samarth. "Segregation analysis of paracentric inversions in human sperm." Montpellier 1, 2008. http://www.theses.fr/2008MON1T002.
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Les inversions paracentriques sont des anomalies chromosomiques généralement considérées comme inoffensives. Toutefois, des cas de porteurs de chromosomes remaniés issus d'inversions paracentriques ont été rapportés, soulignant la nécessité d'étudier le comportement méiotique de ces anomalies. Seules quelques études ont été pratiquées, utilisant la technique de fécondation croisée Homme-Hamster, le typage génétique des spermatozoïdes (sperm typing) ou l'hybridation in situ fluorescente (FISH) par marquages centromériques ou télomériques. Afin d'améliorer l'efficacité de l'étude méiotique des inversions paracentriques, nous avons développé l'utilisation des sondes BAC qui permettent une localisation chromosomique précise des points de cassures chromosomiques et l'identification de tous les produits méiotiques des inversions dans le sperme humain. Les points de cassures et la ségrégation méiotique de 3 inversions paracentriques, inv(5)(q13. 2q33. 1), inv(9)(q21. 2q34. 13) et inv(14)(q23. 2q32. 13), ont ainsi été déterminés. Les taux de recombinants observés dans ces 3 inversions varient de 3,72% à12,55%. Cette localisation des points de cassures et l'analyse des séquences d'ADN adjacentes sont essentielles pour mettre en évidence la formation de boucles d'inversion, pour déterminer le risque de recombinaison à terme, ainsi que pour étudier les mécanismes méiotiques de formation des recombinaisons. Ainsi, la présence de régions d'ADN riches en recombinaisons et en duplications inter-chromosomiques a été mise en évidence, en complément de la formation de recombinants chromosomiques. Par ailleurs, une nouvelle technique de FISH multi-couleurs 3D (3D MCB FISH) a été adaptée aux spermatozoïdes humains pour l'analyse in situ des ségrégations. Cette approche permet de visualiser in situ les inversions paracentriques et d'estimer la fréquence de tous les types de recombinants issus de boucles d'inversion, de recombinaisons U-loop ou de processus de cassure/fusion des chromatides-soeurs.
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Douet-Guilbert, Nathalie. "Dissection cytogénétique des anomalies du chromosome 5 et du chromosome 20 dans les syndromes myélodysplasiques." Brest, 2011. http://www.theses.fr/2011BRES3206.
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Les syndromes myélodysplasiques (SMD) sont des hémopathies malignes chroniques d’origine myéloïde caractérisées par une hétérogénéité clinique et biologique. Les anomalies chromosomiques, principalement déséquilibrées, sont présentes chez 50 % des patients atteints de SMD après étude en cytogénétique. Parmi les anomalies chromosomiques, les anomalies du chromosome 5 et du chromosome 20 sont récurrentes. L’étude systématique, par hybridation in situ fluorescente (FISH) avec des sondes spécifiques de ces remaniements, a permis la caractérisation de leur structure puis l’identification de leurs points de cassure afin de délimiter leurs régions délétées et conservées. Des régions communes délétées (RCD) et conservées (RCC) ont alors été déterminées. Ce travail a consisté à spécifier les anomalies des chromosomes 5 et 20 en délétions pures, dérivés de translocation, dérivés complexes, dicentriques, tricentriques, isochromosomes et isodérivés. Nous avons identifié des RCD et/ou des RCC pour chaque sous-groupe d’anomalies chromosomiques. Pour l’ensemble des réarrangements du chromosome 5, nous n’avons pas déterminé de RCD, mais la région la plus souvent délétée est la région 5q31. 1 à 5q31. 2 qui comprend notamment les gènes EGRI, CTNNAI. Cette étude a démontré l’existence d’une RCC comprenant la région qui s’étend de 5p10 à 5p13. 1 et qui comprend des gènes probablement impliqués dans la survie et la prolifération cellulaires. La perte des gènes APC et NPM1 est variable dans les remaniements du chromosome 5. L’haploinsuffisance de ces gènes peut expliquer les différents phénotypes des SM. D. Concernant l’ensemble des anomalies du chromosome 20, nous n’avons pas identifié de RCD, ni de RCC. Cependant la région la plus souvent délétée est la bande 20q12 et les régions les plus conservées sont les sous-bandes 20q11. 21 et 20ql3. 13, impliquant également des oncogènes ou gènes suppresseurs de tumeurs. Ce travail montre également l’implication du gène ASXL1 qui peut être délété, conservé, amplifié ou rompu. L’expression variable de ce gène pourrait expliquer les répercussions cliniques différentes des SMD avec anomalies du chromosome 20. Etant donné l’hétérogénéité des remaniements des chromosomes 5 et 20, l’analyse cytogénétique, incluant l’étude des régions spécifiques dos chromosomes 5 et 20, par les techniques de FISH, est nécessaire afin de mieux comprendre les mécanismes oncogénétiques des SMDMyelodysplastic syndromes are a heterogeneous biological and clinical entity in myeloid hemopathies. Clonal cytogenetic abnormalities are observed in 50% of the patients. Rearrangements of chromosomes 5 and 20 are recurrent in MDS. Precise characterization of rearrangements of chromosomes 5 and 20, delineation of deleted and retained regions were performed by fluorescent in situ hybridization (FISH) with specific probes. We determined commonly deleted regions (CDR) and commonly retained regions (CRR). This work allowed the specification of structural rearrangements in true deletions, derivatives from translocation, complex derivatives, dicentrics, tricentrics, isochromosomes and isoderivatives. We identified CDR and/or CRR in each group with chromosomal abnormalities. No CDR was observed in the whole group of chromosome 5 rearrangements, but the most frequently deleted region was Sq31. 1 -5q31. 2 band. A CRR was observed from 5p10 to 5p13. L. Bands containing genes involved in cell survival and proliferation. The loss of APC and NPM1 genes was variable, suggesting that haploinsufficiency or not could explain different phonotypes in MDS. Concerning the whole group of chromosome 20 rearrangements, neither RCD nor RCC was identified. However, the most commonly deleted region was 20q12 and die most retained regions were 20q11. 21 and 20q13. 13 involving oncogenes and tumor suppressor genes. In this study, the ASXL1 gene was found deleted, retained, amplified or disrupted. Variable expression of ASXL1 may explain different clinical effects of MDS with chromosome 20 rearrangements. Cytogenetic analysis, including study of specific regions of chromosomes 5 and 20 by FISH, is necessary to understand the oncogenetic mechanisms involved in MDS
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Saut, Noëmie. "Délétions du chromosome Y et infertilité chez l'homme et chez la souris." Aix-Marseille 2, 2001. http://www.theses.fr/2001AIX20674.
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ROUGNY, YVES. "Aberrations chromosomiques : etude retrospective de 116 dossiers observes de 1979 a 1989 a la clinique obstetricale de l'hopital edouard herriot (lyon)." Lyon 1, 1992. http://www.theses.fr/1992LYO1M161.
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Henry, Marianne Patricia. "The genomic health of human pluripotent stem cells." Thesis, Brunel University, 2018. http://bura.brunel.ac.uk/handle/2438/17081.
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Human pluripotent stem cells are increasingly used for cell-based regenerative therapies worldwide, with the use of embryonic and induced pluripotent stem cells as potential treatments for a range of debilitating and chronic conditions. However, with the level of chromosomal aneuploidies the cells may generate in culture, their safety for therapeutic use could be in question. This study aimed to develop sensitive and high-throughput assays for the detection and quantification of human pluripotent stem cell aneuploidies, to assess any changes in their positioning in nuclei, as well as investigate the possible roles of lamins in the accumulation of aneuploidies. Using Droplet Digital PCR™, we optimised the detection of aneuploid cells in a predominantly diploid background. An assay was established for the sensitive detection of up to 1% of mosaicism and was used for the monitoring of low-level chromosome copy number changes across different cell lines, conditions and passages in the human pluripotent stem cells. In addition, fluorescence in-situ hybridisation was used to map genes ALB and AMELX on chromosomes 4 and X, respectively, in karyotype-stable chromosome X aneuploid lymphoblastoid cell lines. Our results demonstrated significant alternations in the gene loci positioning in the chromosome X aneuploid cell lines. Using the same established method, the positioning of ALB and AMELX was monitored, alongside the genomic instability with ddPCR™, in the different human pluripotent stem cell lines, conditions and passage. We demonstrated a highly plastic nuclear organisation in the pluripotent stem cells with many changes occurring within a single passage. Furthermore, these results were not exclusive to a single cell line or condition, regardless of the presence or absence of feeder cells and of passage number, and the flexibility of the chromatin organisation remained throughout the duration of the study. We demonstrated high levels of genomic instability with recurrent gains and losses in the AMELX copy number in the human embryonic stem cells during the course of our study, however no significant changes in their gene loci positioning from these abnormalities were observed. xvi | P a g e Additionally, we observed reduced levels of lamin B2 in the aneuploid lymphoblastoid cell lines and complete loss in some hPSC samples. Our results support recent findings that suggest a link between lamin B2 loss and the formation of chromosome aneuploidies in cell culture. In conclusion, our data demonstrates several key novel findings. Firstly, we have established a sensitive technique for the detection of up to 1% mosaicism, which to our knowledge is the most sensitive assay currently available. Secondly, we showed significant changes in the gene loci positioning between aneuploid and diploid cell lines. Thirdly, utilising our novel ddPCR™ assay, we demonstrated the karyotypical instability of hPCSs with consistent gains and/or loses of gene copy numbers in a short period of time in culture. When studying the effects of different growth conditions, we showed that the karyotypical instability was not exclusive to a single condition or a combination of conditions, and what is more, the karyotypical abnormalities detected were not observed to change the gene positioning of hPSCs significantly, with the genome organisation remaining plastic. Finally, our results support a potential association of lamin B2 loss and karyotypical instability. We conclude that more sensitive and robust techniques need to be readily used by clinicians for the screening of potential therapeutic hPSCs.
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Labbé, Marine. "Vers des modèles murins d'aneuploi͏̈die pour la région Hrmt111-Cstb homologue à la partie télomérique du chromosome 21 humain." Orléans, 2003. http://www.theses.fr/2003ORLE2028.
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La Trisomie 21 (T21) et la Monosomie 21 (M21) humaines entraînent de nombreuses perturbations du développement. L'étude de patients n'a pas permis de résoudre les relations génotype-phénotype nécessitant alors la création de modèles animaux. Il n'existe pas de modèle de M21 et les modèles murins de T21 actuels ne miment pas tous les phénotypes du syndrome. Nous avons donc décidé de créer de nouveaux modèles murins de T21 et de M21 en recombinant, par le système CRE-loxP, la région entre les gènes Cstb et Hrmt1l1 portée par le chromosome 10 absente dans les modèles. Des sites loxP ont ainsi été insérés au niveau de ces gènes en cellules ES afin d'obtenir la duplication et la délétion de la région in vitro grâce au système HPRT et in vivo par la stratégie TAMERE avec les lignées de souris dérivées des clones ES simples recombinants. Nous avons pour l'instant obtenu un mutant hypomorphe pour Hrmt1l1, un modèle de trisomie pour Cstb et un modèle de monosomie conditionnelle pour la région
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Finley, Jennifer C. "Telomere length and chromosomal instability in the neoplastic progression of Barrett's esophagus /." Thesis, Connect to this title online; UW restricted, 2003. http://hdl.handle.net/1773/6343.
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Riegel, Mariluce. "The application of fluorescent in situ hybridization for gene mapping, determination of chromosome aberrations, and DNA replication studies /." Zürich, 2006. http://opac.nebis.ch/cgi-bin/showAbstract.pl?sys=000253511.
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Nugoli, Mélanie. "Instabilité génétique des cancers du sein et étude à haute résolution des anomalies quantitatives du bras long du chromosome 1 (1q)." Montpellier 2, 2003. http://www.theses.fr/2003MON20116.
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Barinova-Melenkova, Natalja. "Anaphase bridges generated by dicentric chromosomes break predominantly at pericentromeric regions and internal telomeric sequences." Thesis, Paris 11, 2015. http://www.theses.fr/2015PA112101.
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Dans la plupart des eucaryotes, il n’existe qu’une seule région centromérique par chromosome et celle-ci est capable d’être liée au fuseau mitotique via le complexe du kinétochore. Dans ce contexte, la présence de deux centromères est un défi pour une séparation normale. Au cours de la mitose, la capture des deux centromères de la même chromatides vers les pôles opposés génère un pont d’anaphase résultant en une rupture entre les centromères. Les extrémités libérées peuvent être fusionnées bout à bout recréant ainsi un dicentrique. Le chromosome entre alors dans un cycle de Rupture Cassure Pont, capable quelques cycles d’entrainer des modifications profondes du nombre de copies de gène qui peuvent contribuer à l'oncogenèse et résistance à la chimiothérapie. Malgré son importance, le mécanisme de rupture reste pour une grande partie inexploré. Ce projet permet l’analyse de la rupture des chromosomes dicentriques en utilisant le modèle de la levure bourgeonnante, Saccharomyces cerevisiae. Nous utilisons des souches dicentriques conditionnelles dans lequelles un chromosome, portant un centromère conditionnel sous le contrôle de deux promoteurs inductibles au galactose, est fusionné à un autre chromosome natif par recombinaison homologue. Nous avons observé que les chromosomes dicentriques ont tendance à casser dans le voisinage des deux centromères. La région de la rupture se répand sur ~ 30 kb vers l'autre centromère. Une insertion d’un fragment d’ADN 1-kb possédant un centromère ectopique dans un chromosome avec un centromère conditionnelle établit un point chaud d’environs 30 kb indiscernables des points chauds à centromères natifs. En outre, la taille de zone de rupture n’est pas corrélée à la distance intercentromerique (des intervalles de 30-600 kb ont été testés). Cela indique que la plus forte propension à rompre est une conséquence de la structure ou de la fonction des centromères et est sans rapport avec les séquences environnantes des chromosomes. Il est encore difficile de savoir si la rupture aux centromères a une fonction physiologique, mais nous pouvons supposer que ce point chaud peut favoriser les réarrangements d'ADN dans ces régions permettant ainsi l’inactivation du centromère et donc le retour à un caryotype stable. Globalement dans la S.cerevisiae, les dicentriques cassent dans les régions péricentromériques ou dans les fusions de télomères quand ils sont présents. Fait intéressant, les séquences télomériques internes, à savoir les répétitions TG₁₋₃, établissent plusieurs points chauds de rupture à une fréquence similaire. En perspective, il serait intéressant d'aborder les questions suivantes : 1) Quelles sont les caractéristiques qui rendent une région plus sujette à la casse ? 2) Quelles sont les positions de rupture au niveau des nucléotides ? 3) Existe-t-il un contrôle de la cassure des chromatides exercé dans la cellule ? 4) Quelle peut être la fonction biologique des points chauds de cassures ?In most eukaryotes, there is one defined centromeric region per chromosome that links it to the spindle apparatus via the kinetochore complex. In this context, the presence of two centromeres is a challenge for an accurate segregation. During mitosis, the capture of the two centromeres of the same chromatid to opposite poles generates anaphase bridges that results in breakage between the centromeres. The released ends can be fused end-to-end thus recreating dicentric. It enters breakage-fusion-bridge cycles that, in multiple rounds, can result in large gene copy number alterations that can contribute to oncogenesis and chemotherapy resistance. Despite of its significance, the mechanism of breakage remains for a large part unexplored. This project adresses the dicentric breakage using a budding yeast, Saccharomyces cerevisiae. We use conditional dicentric strains, where a chromosome, bearing a conditional centromere under the control of two galactose-inducible promoters, is fused to another native chromosome by homologous recombination. We observed that dicentric chromosomes tend to break in the vicinity of the two centromeres. The breakage region spreads over ~30 kb towards the other centromere. An insertion of a 1-kb ectopic centromere in a chromosome with a conditional centromere establishes a ~30 kb hot spot indistinguishable from the hot spots at native centromeres. Furthermore, the size of breakage region is unrelated to an intercentromeric distance (30-600 kb intervals were tested). This indicates that the higher propensity to break is a consequence of centromere structure or function and is unrelated to the native surrounding sequences. It is yet unclear whether breakage at centromeres has a physiological function but we can speculate that this hot spot may favour local DNA rearrangements that result in centromere inactivation and thus the return to a stable karyotype. Overall in budding yeast, dicentrics break at pericentromeric regions or at the telomere fusions when they are present. Interestingly, internal telomeric sequences, i.e. TG₁₋₃ repeats, establish several breakage hot spots with a similar frequency. In perspective, it would be interesting to address the following questions: 1) What are features that make a region more prone to breakage? 2) What are the positions of breakage at nucleotide level? 3) Is there a coordination of dicentric chromatid breakage? 4) What can be the biological function of dicentric breakage hot spots?
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Degerman, Sofie. "The immortalization process of T cells with focus on the regulation of telomere length and telomerase activity /." Doctoral thesis, Umeå : Umeå University, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-33466.
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Thenet, Delphine. "An investigation into the use of 3D microscopy for the study of radiation-induced chromosome aberrations and nuclear architecture." Thesis, Kingston University, 2012. http://eprints.kingston.ac.uk/26573/.
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Cellular exposure to ionising radiation (IR) generates chromosome aberrations (CA) that in turn lead to gene mutation and cell death. Although radiation-induced CA are known to result from the misrepair or lack of repair of DNA damage, the exact details of the conversion of such damage to CA remains unclear especially with regard to those CA that involve two or more chromosomes. In interphase cells, chromosomes occupy discrete territories that under specific conditions appear conserved within any cell type. Territories appear to have both structural and functional importance and their position within the nucleus is apparently dynamic and changes during the cell cycle. The existence of territories suggests that in three dimensions, chromosomes differ in their spatial relationship. The aims of this thesis were to develop methods for 3D analysis and visualisation of chromosome territories in human primary fibroblasts and bladder carcinoma (RTl12) cell nuclei to enable chromosome characterisation. The relationship between CA formation following irradiation and nuclear architecture was investigated using fluorescence in situ hybridization and confocal microscopy in the two cell lines. Analysis and visualisation methods were developed and applied in order to assess chromosome properties in relation to the nucleus. Chromosome 1 and chromosome 2 territories were successfully imaged in non-irradiated and irradiated cell nuclei. 3D analysis and visualisation enabled the identification and quantification of complete and fragmented chromosomes territories. The methods developed may thus help to elucidate the mechanisms of radiation induced chromosome aberrations and hence have application in cancer cell biology.
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GUYENON, SYLVAIN. "Le centre de diagnostic antenatal de valence : bilan de deux annees et demie de diagnostic antenatal des aberrations chromosomiques, par l'etude du caryotype apres amniocentese, au centre hospitalier de valence (drome) de janvier 1989 a juin 1991." Lyon 1, 1993. http://www.theses.fr/1993LYO1M257.
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Wong, Chi-wai. "High resolution mapping of loss of heterozygosity and chromosomal aberrations using oligonucleotide single nucleotide polymorphism genotyping arrays in colorectal adenoma to carcinoma progression." Click to view the E-thesis via HKUTO, 2006. http://sunzi.lib.hku.hk/hkuto/record/B3871923X.
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Ruangpratheep, Chetana. "Aberrations of DPPA3 (STELLA), EDR1 (PHC1), GDF3, and NANOG, putative stem cell-associated genes on chromosome 12, in breast carcinoma." Thesis, University of Leicester, 2012. http://hdl.handle.net/2381/10944.
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Introduction: Chromosome 12p13 has been reported to show gain/amplification in some breast cancers. This region contains putative stem cell-associated genes: DPPA3, EDR1, GDF3, and NANOG, but these genes have not been investigated in breast previously. Hence, the aim of this thesis was to study their role in breast carcinomas. Materials and methods: The mRNA expression was evaluated in normal and malignant breast tissues using TaqMan® gene expression assays. Western blotting and immunohistochemistry were used for determination of protein expression. Copy number variations (CNVs) were assessed by TaqMan® copy number assays (CNAs) and Affymetrix® genome-wide human single nucleotide polymorphism (SNP) array 6.0. Results: Expression of DPPA3, EDR1, and NANOG was undetectable in normal breast tissue, but there was variable expression in breast carcinomas (BC) where expression of these genes tended to be higher in surrounding normal breast tissue. GDF3 was not expressed in BC. At the 95% confidence interval, higher expression of DPPA3 in BC was related to axillary lymph node metastasis; lower expression of DPPA3, EDR1, and NANOG correlated with high grade; and lower expression of NANOG was found in tumours of size > 2.0 cm. Both TaqMan® CNAs targeting each gene individually and SNP 6.0 genome wide array revealed complicated patterns of CNVs for these genes. The majority of BC had gain of DPPA3 but loss (deletion) of EDR1 and NANOG. However, there was no significant correlation between CNVs and either mRNA expression or protein expression. Conclusion: Variable aberrations in copy number and expression of DPPA3, EDR1, and NANOG genes in the chromosome 12p13 region are associated with aggressive characteristics of breast carcinomas.
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Empke, Stéfany Lopes Lucas. "Caracterização fenotípica em indivíduos com microarranjos na região cromossômica 22q11." Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/61/61132/tde-07032016-173433/.
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Objetivo: Descrever as manifestações clínicas de indivíduos com hipótese diagnostica da Sindrome de deleção 22q11 (SD22q11) confirmados por testes genéticos, na primeira avaliação e durante o acompanhamento dos mesmos em avaliações subsequentes para uma melhor definição do curso natural da doença. Local: Laboratório de Genética e Citogenética Humana do HRAC-USP Bauru/SP. Casuística e metodologia: O presente trabalho é retrospectivo e analisou os dados de prontuários de 72 indivíduos cadastrados no HRAC-USP, os quais receberam hipótese diagnóstica da SD22q11 e foram confirmadas por teste genético (MLPA ou FISH). A avaliação envolveu a analise dos dados relatados por todos os setores do HRAC-USP. Resultados e discussão: Foramanalisados 72prontuários deindivíduos com a SD22q11. Constatamos que a idade media dos indivíduos quando do cadastro no HRAC-USP foi de seis anos. Também constatamos que houve um longo período de tempo entre os retornos ao hospital e que, nesses retornos, nem todas as especialidades foram contempladas. Esses fatos prejudicaram a analise da historia natural da anomalia em questão. Com relação às características fenotipicas, observamos a presença de sinais clínicos típicos, como por exemplo: face alongada, lábios finos, hipoplasia alar, anormalidades menores na orelha, dígitos longos e fendas palpebrais, fissuras labiopalatinas, cardiopatias congenitas, dificuldade de aprendizagem, atraso de linguagem e distúrbios comportamentais. A fissura oral foi à manifestação otorrinolaringológica mais frequente, presente em 75% dos pacientes, onde as fissuras submucosas foram as mais frequentes (43%). As características cognitivas como, atraso de fala (87%), dificuldades de aprendizagem (95%) e distúrbios comportamentais (81%), tiveram um resultado significativo, descritas em quase todos os indivíduos. As cardiopatias congênitas estavam presentes em 47,2% dos prontuários analisados. De um modo geral, comparando a frequência dos sinais clínicos encontrados neste trabalho com dados da literatura, constatamos que as frequências encontram-se dentro do esperado. Conclusão: A maioria dos indivíduos cadastrados no HRAC-USP, pertencentes ao grupo de estudo, apresentou idade superior a 06 anos. Portanto, a observação do curso natural da historia da SD22q11 para avaliar características fenotípicas que surgissem ao longo da evolução clinica do indivíduo e que pudessem ajudar no diagnóstico, ficou prejudicada. Mesmo nos casos onde o indivíduo foi cadastrado no HRAC-USP com idade inferior a dois anos, o diagnóstico foi tardio devido a falta de uma ação multidisciplinar e interdisciplinar no hospital. Mesmo não sendo possível avaliar as características fenotípicas surgidas durante a historia natural da doença, constatamos que as manifestações clínicas relatadas nos prontuários cursam com as características da SD22q11 e em frequências que corroboram com as da literaturaTo describe clinical manifestations observed in medical records of individuals registered in the hospital with a diagnostic hypothesis of 22q11.2DS confirmed by genetic tests (MLPA OR FISH), since the first assessment in the HRAC-USP and during the follow up of these individuals in subsequent assessments, in order to achieve a better definition to the natural courses of the disease. Local: Laboratory of Human Genetics and Cytogenetics (HRAC-USP Bauru/SP). Methods: This retrospective study analyzed 72 medical records of individuals registered at the HRAC-USP, who were diagnosed with 22q11DS and who had this diagnosis confirmed by a genetic test (MLPA OR FISH). The assessment concerned the analysis of reported data in all sectors of the HRAC-USP. Results and Discussion: 72 medical records of individuals with 22q11DS were analyzed. It was verified that the average age of individuals when registering at the HRAC-USP was six years old. It was also verified that it took a long period of time for these individuals to return to the hospital and, when they did, not all specialties were contemplated. These facts harmed the analysis of the natural history of the anomaly. About the phenotypic characteristics, some typical clinical signs were observed, such as: long face, thin lips, hypoplasia nasal alar, minor abnormalities in the ear, long digits and narrow palpebral fissures, palatal abnormalities, congenital heart defects, learning disabilities, delay speech and behavioral disorders. An oral cleft was the most frequent otorhinolaryngology manifestation, present in 75% of the patients; among which submucous cleft palate were the most frequent (43%). Cognitive features such as, delay speech (87%), learning disabilities (95%) and behavioral disorders (81%) had a significant result, described in almost all individuals. Congenital heart defects were observed at 4% to 48% of individuals with 22q11.2DS, in this study it was observed in 47.2%. In general, comparing the frequency of some clinical signs observed in this study with the literature data, it was verified that the frequencies were within expectations. Conclusion: Most of the individuals registered at the HRAC belonging to the study group were over 6 years old. Therefore, the observation of natural course of the history of 22q11DS to evaluate the phenotypic characteristics that would arise during the clinical evolution of the individual and that could help in the diagnosis was harmed. Even in cases when the individual was registered at the HRAC-USPunder the age of two, the diagnosis was delayed due to lack of a multidisciplinary and interdisciplinary action in the hospital. Even not being possible to measure the phenotypic characteristics that emerged during the natural history of the disease, it was verified that the clinical manifestations reported in the records occur with the 22q11DS characteristics and in frequencies that corroborate with the literature
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Ferfouri, Fatma. "Anomalies génétiques et épigénétiques de l’ADN spermatique et infertilité masculine." Versailles-St Quentin en Yvelines, 2012. http://www.theses.fr/2012VERS0054.
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L’infertilité masculine parait augmenter depuis plusieurs décennies. Ses étiologies sont multiples, mais les causes génétiques et épigénétiques paraissent importantes. Nous avons dans cette thèse étudié différentes causes génétiques et épigénétiques d’infertilité en mettant en évidence les anomalies portées par les spermatozoïdes et parfois transmissibles au conceptus. Ce travail comporte trois parties, à savoir, tout d'abord, les infertilités associées à des anomalies du caryotype constitutionel en étudiant les conséquences pour le risque chromosomique porté par les spermatozoïdes avec le risque évalué sur tous les spermatozoïdes puis, les infertilités, à caryotype constitutionel normal, dont l’origine génique a parfois été démontrée et où la morphologie spermatique est altérée avec les spermatozoïdes macrocéphales, les spermatozoïdes globozoocéphales et les spermatozoïdes à larges ou petites vacuoles et enfin, les anomalies de la méthylation de l’ADN dans les différentes étiologies d’azoospermie. Ces approches ont un triple intérêt car elles permettent d'évaluer les risques pour le conceptus, de guider la prise en charge des patients et le choix des spermatozoïdes à injecter dans l’ovocyte. A plus long terme grâce à une compréhension des mécanismes en jeu, prévenir des infertilités et proposer de véritables solutions thérapeutiquesThe male infertility seems to increase for several decades. Infertility etiologies are multiple, but the genetic and epigenetic causes are important. Here, we tried to study, the abnormalities carried by spermatozoa and sometimes transmissible in the conceptus. This work contains three parts, in a first time, the infertility linked with abnomalities of constitutionel karyotype by studying the consequences for the chromosomal risk with the risk estimated on all spermatozoa, in a second time, the infertility, with normal constitutionel karyotype, where the genetic origin was sometimes demonstrated and sperm morphology altered with macrocephalic sperm, Globozoospermia and spermatozoa with large or small vacuoles and in fine, DNA methylation abnormalities in various azoospermic aetiologies. These approaches have a triple interest because, it estimate the risks for conceptus and advice patients care, guide the choice of spermatozoa to be injected in the oocyte
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Lu, Wenqing. "Phenotypic impact of inversions in yeast genome." Electronic Thesis or Diss., Sorbonne université, 2021. https://accesdistant.sorbonne-universite.fr/login?url=https://theses-intra.sorbonne-universite.fr/2021SORUS514.pdf.
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Les génomes sont des structures hautement dynamiques et les grandes variations structurelles (SVs) des chromosomes, telles que les inversions, contribuent à l'évolution des génomes et à l'adaptation des espèces. Il est essentiel de comprendre l'impact fonctionnel des inversions sur la diversité phénotypique, car il existe de plus en plus de preuves que les inversions joueraient un rôle important dans les variations phénotypiques. Afin d'expliquer l'impact phénotypique des inversions, nous avons choisi la levure de boulangerie comme modèle eucaryote unicellulaire dans notre travail. Sur la base d'un catalogue de 104 événements d'inversion caractérisés parmi un panel de 142 assemblages de génomes complets, nous nous sommes concentrés sur une inversion spéciale de 32kb localisée sur le chromosome XIV et qui est trouvée de manière récurrente dans diverses souches de Saccharomyces cerevisiae et S. paradoxus. Nous avons utilisé la méthodologie CRISPR/Cas9 d'édition du génome pour générer des bibliothèques de souches de S. cerevisiae contenant cette région dans les deux orientations par l'introduction de 2 cassures double-brin ((DSB pour Double-Strand Break) de l'ADN aux extrémités de cette région. Nous avons construit ce type d'inversions dans 3 souches hôtes présentant des fonds génétiques différents, S288C, YPS128 et Y12. Afin de tester les relations entre ce type de variation génétique et les traits phénotypiques, nous avons étudié l'impact fonctionnel des inversions pendant les cycles cellulaires sexuels et végétatifs, y compris le taux de croissance dans différentes conditions de culture, l'efficacité de la sporulation, l'efficacité des croisements et la viabilité des spores. Ce travail nous a permis de déterminer la contribution de cette inversion aux variations phénotypiques et son rôle adaptatif au cours de l'évolutionGenomes are highly dynamic structures and large-scale Structural Variations (SVs) of chromosomes such as inversions contribute to genome evolution and species adaptation. Understanding the functional impact of inversion on phenotypic diversity is essential because there are growing evidence that inversions play an important role in phenotypic variation. For the purpose of explaining the phenotypic impact of inversions, we choose yeast as single cell eukaryotic model in our work. Based on a catalogue of 104 inversion events characterized among a panel of 142 complete genome assemblies, we focused on a special 32kb inversion on chromosome XIV that is recurrently found in various strains of Saccharomyces cerevisiae and S. paradoxus. CRISPR/Cas9 methodology of genome editing is applied to generate strain libraries in S. cerevisiae containing this region in both orientations through the introduction of DNA double-strand breaks (DSBs) at the inversion boundaries. We constructed such inversion models in 3 different host strains with different genetic background, S288C, YPS128 and Y12. In order to test the relationships between this type of genetic variation and phenotypic traits, we investigated the functional impact of the inversions during both sexual and asexual cell cycles, including growth ratio in different culture conditions, sporulation efficiency, mating efficiency and spore viability. This work allows us to determine the contribution of inversions to phenotypic variations and their adaptive role during evolution
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Takagi, Takehisa. "The influence of DNA ploidy of a human tumor cell line on the frequencies of micronuclei or chromosome aberrations after irradiation." Kyoto University, 1999. http://hdl.handle.net/2433/181261.
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Toujani, Saloua. "Du chromosome au gène par un criblage global des altérations génomiques dans la malignité pour isoler de nouvelles cibles thérapeutiques." Thesis, Paris 11, 2012. http://www.theses.fr/2012PA11T027/document.
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Le cancer est désormais considéré comme une maladie génomique de la cellule. Les moyens d’étude de l’oncogénome étaient basés sur les différentes modalités du caryotype, peu résolutif. L’application des techniques de micromatrices d’oligonucléotides, notamment l’aCGH, a permis une avancée majeure dans la caractérisation des génomes des cancers.La première partie de notre travail a porté sur les lymphomes de Burkitt (LB), caractérisés par une translocation entre un gène d'immunoglobuline et MYC. L’étude portait sur 12 tumeurs primaires et 15 lignées cellulaires. L’aCGH (44K et 244K), concordait avec les cytogénétiques morphologique et moléculaire (FISH) sauf pour les translocations. Plus de la moitié des variations du nombre de copies (<2Mb) étaient des polymorphismes (CNV). Les anomalies pathologiques (CNA) (n=136) intéressaient les régions suivantes : gains 1q, 13q, 7q, 8q, 2p, 11q et 15q ; pertes 3p, 4p, 4q, 9p, 6p, 17p, 6q, 11pterp13 et 14q12q21.3. Vingt régions minimales critiques (MCR) d’une taille varie entre 0.07-71.36 Mb, étaient délimitées. Trois MCR étaient identifiées sur le 1q : 1q21.1q25.2, 1q32.1 et 1q44. La région proximale de 1q21.1q25.2 était le siège d’une amplification, contenant entre autres les gènes BCA2, PIAS, BCL9. L’étude par transcriptome, sur 15 lignées, a démontré la surexpression uniquement de BCL9, remanié dans les LAL B et faisant partie de la voie de signalisation de MYC. Sur la région 11q23.1, le gain intéressait le gène POU2AF1 dont le messager était élevé. La MCR 13q31.3q32.1 était le siège d’une amplification contenant ABCC4, et le polycistron miR17-92. La corrélation des résultats d’aCGH à ceux du transcriptome et du mirnome ont démontré une surexpression du miR17-92 qui contrôle le développement des lymphocytes B et intervient dans la voie de signalisation de MYC. Sur le 9p21.3, la perte emportait le locus p16INK4A/p15INK4B. Le transcriptome avait démontré une sous expression de p15INK4B. Le locus p16INK4A/p15INK4B contrôle les 2 voies majeures, pRB et p53.La seconde partie de notre travail a consisté à étudier 17 tumeurs congelées de carcinomes adénoïdes kystiques (CAK) par aCGH 44K. Les CNA étaient validées par FISH et/ou MLPA. L’expression protéique était étudiée par immunohistochimie. Les pertes excédaient les gains (41 versus 24). La t(6;9)(q23;p22) récurrente dans les CAK était indétectable car équilibrée. Dans un seul cas, le der(6)t(6;9) est probablement présent sur le profil aCGH. Les MCR les plus fréquentes (-6q22 et -6q24) n’incluaient pas 6q23. Treize MCR étaient identifiées. La MCR délétée en 8q impliquait le miR-124A2 qui régule les gènes CDK6 et MMP2. Sur le 9p21.3, le locus p16INK4A/p15INK4B était de nouveau perdu. Des gains isolés étaient observés au niveau des locus CCND1, KIT/PDGFRA/KDR, MDM2 et JAK2. Le gène MDM2, qui était amplifié sous forme de double minutes, est un élément clé de l’axe p16INK4A-ARF-p53.Pour la troisième partie de notre travail nous avons étudié 60 tumeurs primaires d’adénocarcinomes pulmonaires (AD) de non fumeur par aCGH (244K). Dans 50/60 tumeurs, le nombre de MCR était de 14. Cinq MCR contenaient un seul gène (MOCS2, NSUN3, KHDRBS2, SNTG1 et ST18). Une MCR gagnée, 5q35, contenait le gène NSD1. Une amplification, sous forme de HSR et mise en évidence par FISH, intéressait l’oncogène FUS. Une PCR quantitative avait permis de confirmer la surexpression FUS. A notre connaissance, c’est la première étude qui incrimine le gène FUS dans la carcinogenèse de l’AD du non-fumeur. D’autres gènes étaient également impliqués : ARNT, BCL9, CDK4, p15INK4B, EGFR, ERBB2, MDM2, MDM4, MET, MYC, NKX2-1 et KRAS. Un clustering non supervisé avait permis de dégager un groupe avec un gain de MYC ; un autre groupe caractérisé par la perte des gènes suppresseurs RB et WRN et un dernier groupe caractérisé par un gain 7p et 7q, et présentait une fréquence élevée de mutations de l’EGFR. Dans 10/60, le nombre de CNA était très rare et aucune MCR n’était détectéeMuch of our current understanding of cancer is based on the hypothesis that it is a genetic disease, arising as a clone of cells that expand in an unregulated fashion because of somatically acquired mutations. High-throughput tools for nucleic acid characterization, such as array comparative genomic hybridization (aCGH), now provide the means to conduct comprehensive analyses of somatic anomalies in the oncogenome.In the first part of our work we have carried out a fine mapping of additional chromosomal anomalies in Burkitt lymphoma (BL). The hallmark of this disease is the translocation t(MYC;IG). We have applied whole-genome 244K and 44k oligonucléotides aCGH to 15 cells lines and 12 primary tumors of BL respectively. Karyotype and FISH analysis were used to validate aCGH results. As expected, all translocations remained undetectable with aCGH. More than half of the copy number alterations (CNAs) < 2 Mb were mapped to Mendelian CNVs, including GSTT1, and BIRC6. Somatic cell line-specific CNVs localized to the IG locus were consistently observed with the 244 K aCGH platform. Among 136 CNAs, gains were found in 1q, 13q, 7q, 8q, 2p, 11q and 15q. Losses were found in 3p, 4p, 4q, 9p, 13q, 6p, 17p, 6q,11pterp13 and 14q12q21.3. Twenty one minimal critical regions (MCR), (range 0.04–71.36 Mb), were delineated in tumors and cell lines. Three MCRs were localized to 1q: 1q21.1q25.2, 1q32.1 et 1q44. The proximal one was mapped to 1q21.1q25.2 with a 6.3 Mb amplicon (1q21.1q21.3) harboring BCA2, BCL9 and PIAS3. Only BCL9 high level transcrit was noted on oligonucleotide microarray gene expression that was done on 15 cells lines. BCL9, was implicated in a LAL B translocation t(1;14)(q21;q32) and it is a member of MYC pathway. The 13q31.3q32.1, 89.58–96.81 Mb MCR contained an amplicon with several genes. The miR-17-92 cluster, upregulated on mirnome analysis that was done on 15 cells lines, is the gene driver of 13q MCR. The miR-17-92 cluster is a member of MYC pathway. The 9p21.3 MCR harbored p16INK4A/p15INK4B locus which is downregulated. MYC activates ARF,a protein encodes by p16INK4A/p15INK4B locus. . On the second part of our work, a 44k aCGH was applied on 17 frozen adenoid cystic carcinoma (ACC) to delineate with a high resolution the CNA associated with ACC. aCGH results were validated with FISH and/or MLPA. Protein expression was screened with immunohistochemistry analysis. The translocation t(6;9)(q23;p23p24)/ MYB-NFIB recurrent in ACC, was not detected with aCGH. In one case, the der(6)t(6;9) was suspected in the aCGH pattern. There were recurrent gains at 7p15.2, 17q21–25, 22q11–13, and recurrent losses at 1p35, 6q22–25, 8q12–13, 9p21, 12q12–13, and 17p11–13. Thirteen MCR were detected. The recurrent deletion at 8q12.3–13.1 contained miRN124A2 gene, whose product regulates MMP2 and CDK6. The 9p21.3 MCR harbored p16INK4A/p15INK4B locus which was deleted. On 17p11p13, the MCR contained several genes and TP53 was deleted in 2 cases. The MDM2 gene, a member of p16INK4A-ARF-p53 pathway, was amplified and overexpressed in one case. Among the other unique CNAs, gains harbored CCND1, KIT/PDGFRA/KDR, and JAK2. On the third part of this these, a high-resolution 244K aCGH was conducted on 60 frozen lung adenocarcinoma (AD) of never smokers patients in order to establish a catalog of CNA. In 50/60 tumors, fourteen new MCR of gain or loss was noted. One larger MCR of gain contained NSD1.One focal amplification and nine gains contained FUS. NSD1 and FUS are oncogenes hitherto not known to be associated with lung cancer. FUS was over-expressed in 10 tumors with gain of 16p11.2 compared to 30 tumors without that gain. A FUS hsr was observed with FISH screening. FUS was over-expressed in 10 tumors with gain of 16p11.2 compared to 30 tumors without that gain. Other cancer genes present in aberrations included ARNT, BCL9, CDK4, p15INK4B, EGFR, ERBB2, MDM2, MDM4, MET, MYC, NKX2-1 and KRAS
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Flordal, Thelander Emma. "Genetic characterization of hematological malignancies with focul on mantle cell lymphoma /." Stockholm, 2007. http://diss.kib.ki.se/2007/978-91-7357-161-6/.
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Wong, Chi-wai, and 黃志偉. "High resolution mapping of loss of heterozygosity and chromosomal aberrations using oligonucleotide single nucleotide polymorphismgenotyping arrays in colorectal adenoma to carcinoma progression." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2006. http://hub.hku.hk/bib/B3871923X.
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Lindforss, Ulrik. "On the clinical value of genetic analysis in colorectal cancer patients /." Stockholm, 2003. http://diss.kib.ki.se/2003/91-7349-742-8.
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