Dissertations / Theses on the topic 'Chromosomal abnormalities'
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Downie, Sarah Elizabeth. "Detection of chromosomes and chromosomal abnormalities in human sperm." Title page, contents and overview only, 1999. http://web4.library.adelaide.edu.au/theses/09PH/09phd751.pdf.
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Bibliography: leaves 135-151. A study of chromosomal abnormalities and the localisation of chromosomes in human sperm, especially from men with TSD, using fluorescence in situ hybridization (FISH). The project entailed: 1. development of reliable FISH protocols, 2. determination of basline frequencies of aneuploidy, 3. analysis of chromosomal abnormalities in men with severe TSD and 4. assessment of the localisation of individual chromosomes within the sperm head.
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Lahn, Bruce T. 1968. "The human Y chromosome : gene content and chromosomal abnormalities." Thesis, Massachusetts Institute of Technology, 1998. http://hdl.handle.net/1721.1/49655.
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Schouten, Hendricus Constantinus. "Chromosomal abnormalities in hematological malignancies." Maastricht : Maastricht : Datawyse ; University Library, Maastricht University [Host], 1991. http://arno.unimaas.nl/show.cgi?fid=5640.
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Martini, Elena. "Chromosomal abnormalities in human gametes." Maastricht : Maastricht : UPM, Universitaire Pers Maastricht ; University Library, Maastricht University [Host], 1998. http://arno.unimaas.nl/show.cgi?fid=8529.
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Kirkpatrick, Gordon. "Chromosome segregation and meiotic defects in carriers of chromosomal abnormalities." Thesis, University of British Columbia, 2009. http://hdl.handle.net/2429/9705.
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Male carriers of chromosomal abnormalities (CA) are more frequent in the infertile population. These men have higher levels of sperm aneuploidy due to the aberrant segregation of the chromosomes involved in the abnormality. The presence of a CA may also influence the segregation of other chromosomes, in a process known as in interchromosomal effect (ICE). The behaviour of the CA during meiosis may account for the infertility observed in this population. We studied chromosome segregation, ICE and meiotic defects in a variety of CA. In carriers of CA, we determined the segregation patterns of chromosomes involved in the abnormality. With the exception of the carriers of mosaic aneuploidy, we found significantly increased frequencies of unbalanced chromosome complements. We observed ICE in six of twelve carriers, which were confined largely to the acrocentric chromosomes 13 and 21. We compared the frequency of chromosome imbalance in CA carriers with infertile, but karyotypically normal, and found higher levels of sperm aneuploidy than CA carriers or controls.
We observed synapsis and recombination of homologous chromosomes in carriers of chromosomal abnormalities, as well infertile and fertile men. We observed reduced recombination in two of the carriers of CA and in three of the infertile men. Increased synaptic errors were observed in all carriers of CA and in four of the infertile men. We noted an increased proportion of cells lacking sex chromosome recombination in all of the CA carriers. We studied chromosome-specific recombination patterns on chromosomes 13, 18 and 21 and compared those results with levels of aneuploidy in the sperm but observed no relationship. We studied the recombination and sex chromosome association, of the involved chromosomes, in the three carriers of CA, and observed decreased recombination on the involved chromosomes and frequent association between the chromosome abnormality and the sex chromosomes. We report the use of a novel technique for the examination of meiotic cells derived from the ejaculate. We compared spermatocytes, derived from the ejaculate, with testicular derived spermatocytes and found no difference in the frequency of global or chromosome-specific recombination, synaptic errors or proportion of cells at various stages of prophase.
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Iatropoulou, Aikaterini. "Genesis of chromosomal abnormalities during oocyte growth and maturation." Thesis, Imperial College London, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.408762.
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Al, farawati Samer. "Analysis of chromosomal abnormalities in human oocytes and embryos." Thesis, University of Oxford, 2013. http://ora.ox.ac.uk/objects/uuid:da17212b-2713-4e6e-846a-e71549d6eb2f.
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The chromosome constitution of human cleavage stage embryos has been extensively investi-gated using a variety of techniques, revealing high levels of aneuploidy and mosaicism. However, the final phase of preimplantation development, the blastocyst stage has received relatively little attention mostly because it is only recently that embryo culture has become sufficiently well optimised to reliabley generate blastocysts. One of the aims of this study was to examine blastocyst cytogenetics, characterising the extent and variety of aneuploidy and, where possible, determining the origin of the abnormalities detected. Both the frequency of aneuploidy and the incidence of mosaicism were significantly lower in the 52 embryos generated by 20 patients that had successfully undergone the first cellular differentiation, producing trophectoderm (TE) and inner cell mass (ICM). Valuable tools for the detailed chromosomal analysis of blastocysts, used in both research and clinical contexts, were comparative genomic hybridization (CGH) and array CGH (aCGH). However, validation of these methods, especially aCGH, was required in order to verify accuracy. A low error rate and a low misdiagnosis risk were demonstrated. The morphology of 1397 embryos at the cleavage and blastocyst stages from 229 patients was evaluated in relation to their chromosomal complement. The results obtained during this part of the project showed that, in general, there is little correlation between cleavage stage morphology and chromosome status. A weak link between morphology and aneuploidy, however, was found for embryos at the blastocyst stage. Chromosomally normal female embryos had a tendency to grow faster than male embryos at the cleavage stage and therefore tended to achieve superior morphological scores, whereas the trend was reversed at the blastocyst stage. Abnormal embryos carrying types of aneuploidy compatible with formation of a clinically recognised pregnancy had morphologies indistinguishable from those of euploid embryos. This study also aimed to utilise aCGH for the preimplantation genetic diagnosis (PGD) of imbal-ances due to structural chromosome rearrangements (e.g. translocations) in 39 carriers, a total of 139 embryos were assessed. The data obtained revealed that carriers of Robertsonian translocations are at increased risk of aneuploidy affecting additional chromosomes not involved the translocation, a phenomenon known as an interchromosomal effect (ICE). Finally, the clinical outcomes of 300 patients undergoing preimplantation genetic screening (PGS) using aCGH, for various different indications, were evaluated at both the cleavage (795 embryos) and blastocyst stages (1097 embryos). The pregnancy rate following cleavage stage biopsy was significantly lower than following blastocyst stage biopsy. The miscarriage rate was significantly reduced following PGS for patients with recurrent miscarriages. This work provided promising data supporting the clinical use of comprehensive chromosome analysis for the screening or diagnosis of preimplantation embryos and also yielded scientifically useful information concerning the frequency and nature of aneuploidy at the final stage of development before implantation.
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Connor, Jessica. "Chromosomal abnormalities identified in infants with congenital heart disease." University of Cincinnati / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1307441785.
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Yang, Hui. "Chromosome dynamics and chromosomal proteins in relation to apoptotic cell death in yeast." Laramie, Wyo. : University of Wyoming, 2008. http://proquest.umi.com/pqdweb?did=1594496261&sid=1&Fmt=2&clientId=18949&RQT=309&VName=PQD.
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Mansouri, Mahmoud R. "Molecular Characterisation of Structural Chromosomal Abnormalities Associated with Congenital Disorders." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-6887.
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McManus, Damian Terence. "Somatic genetic and chromosomal abnormalities in ovarian and breast carcinoma." Thesis, Queen's University Belfast, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.263336.
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Kuo, Hongqi. "Nuclear and chromosomal abnormalities in human preimplantation development in vitro." Thesis, King's College London (University of London), 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.251676.
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Sanoudou, Depi. "Chromosomal abnormalities in primary neoplasms of the central nervous system." Thesis, University of Cambridge, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.621592.
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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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Pan, Yi. "Molecular cytogenetic investigations of chromosomal abnormalities in prostate and urinary bladder cancers /." Stockholm, 2000. http://kib.ki.se/2000/91-628-4296-X/.
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Curwen, Gillian B. "G₂ chromosomal radiosensitivity in childhood and adolescent cancer survivors and their offspring." Thesis, St Andrews, 2008. http://hdl.handle.net/10023/425.
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Kempski, Helena Maria. "A molecular cytogenetic study of chromosome regions 11q23 and 21q22 in childhood leukaemia." Thesis, University College London (University of London), 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.313659.
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Смірнов, Олег Ювеналійович, Олег Ювенальевич Смирнов, Oleh Yuvenaliiovych Smirnov, Альона Олександрівна Потапова, Алена Александровна Потапова, and Alyona Oleksandrivna Potapova. "Хромосомні хвороби в Сумській області." Thesis, Видавництво СумДУ, 2008. http://essuir.sumdu.edu.ua/handle/123456789/5962.
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Fragouli, Elpida. "The detection of chromosomal abnormalities in human oocytes and preimplantation embryos by molecular cytogenetic analysis." Thesis, University College London (University of London), 2005. http://discovery.ucl.ac.uk/1445491/.
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Chromosome abnormalities are observed very frequently in humans. Several types of structural chromosome abnormalities have been identified, with chromosome translocations, both reciprocal and Robertsonian, being the most common in the population. Balanced carriers of such rearrangements could be at risk of generating abnormal offspring due to the meiotic segregation of the translocation. Preimplantation Genetic Diagnosis (PGD) has allowed the extensive cytogenetic investigation of embryos from such patients with the application of Fluorescent in situ hybridisation (FISH). The first part of this work involved the development of robust three-colour FISH protocols for their clinical application for the PGD for three reciprocal translocations, two different Robertsonian translocations and two cases of suspected gonadal mosaicism. Five of these patients underwent 1-2 cycles of treatment, and 21 normal/balanced embryos were detected and transferred to the maternal uterus. One clinical pregnancy was established with a subsequent live birth of a healthy male infant in a case of a female reciprocal translocation carrier. Extensive FISH examination of the non-transferred embryos showed evidence of post-zygotic mosaicism in 73.4% of them, with chaotic embryos predominating. Both meiotic and mitotic mechanisms leading to chromosome gain and/or loss were identified in this group of embryos.
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Al-Mufti, Raghad Abdul Wahab Mohamed Latif. "Non-invasive prenatal diagnosis of chromosomal abnormalities by isolation of fetal cells from the maternal circulation." Thesis, King's College London (University of London), 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.404600.
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Mantzouratou, A. "Molecular cytogenetic investigation of the origin of chromosomal abnormalities arising in human preimplantation embryos and oocytes." Thesis, University College London (University of London), 2008. http://discovery.ucl.ac.uk/1444324/.
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Introduction: Advances in diagnosis and screening of preimplantation embryos or oocytes for chromosomal abnormalities have helped many couples achieve a normal pregnancy. They also pointed to the fact that numerical and structural chromosomal abnormalities are frequent in human preimplantation embryos and can arise at any point during gametogenesis and meiosis through to early embryonic development and mitotic division. However, information coming from studies in this area is far from complete and uniform.;Aim: To investigate aneuploidy and its mechanisms in human preimplantation embryos and oocytes. To develop protocols and improve on existing molecular cytogenetic techniques for the advance of preimplantation genetic diagnosis or screening (PGD/PGS) in routine clinical analysis. To evaluate the impact of PGD and PGS on the treatment of various types of infertility.;Methods: Fluorescent In situ Hybridisation (FISH) and Comparative genomic hybridisation (CGH) were the main methods used. I) Protocols were developed and implemented for the clinical PGD and PGS program. The PGD protocols included 2 couples with rare structural chromosomal abnormalities II) All untransferred embryos were studied and information was obtained for 101 PGS cycles (77 couples-935 embryos) and 18 PGD cycles for structural chromosomal abnormalities. III) Immature and undivided oocytes were studied using CGH from PGS, PGD and routine IVF couples.;Results and discussion: Specific and highly efficient methods and their clinical application to detect a variety of rare and common chromosomal abnormalities in PGD and PGS embryos were achieved. This study adds to the accumulating evidence showing the extent and mechanisms of genetic abnormalities in human oocytes and preimplantation embryos. It is one of the first studies to identify significant differences in the types of chromosomal abnormalities in embryos from couples with different reproductive history suggesting susceptibility to particular types of aneuploidy in these couples. The problems and effectiveness of PGS and PGD are also discussed.
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Narayanan, Vidhya. "Inverted repeats as a source of eukaryotic genome instability." Diss., Atlanta, Ga. : Georgia Institute of Technology, 2008. http://hdl.handle.net/1853/24774.
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Thesis (Ph.D.)--Biology, Georgia Institute of Technology, 2009.Committee Chair: Lobachev, Kirill; Committee Co-Chair: Chernoff, Yury; Committee Member: Crouse, Gray; Committee Member: Goodisman, Michael; Committee Member: Streelman, Todd.
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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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Hyett, Jonathan A. "Fetal cardiac defects and increased nuchal translucency at 10-14 weeks of gestation." Thesis, King's College London (University of London), 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.391627.
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Hillman, Sarah Christine. "The use of prenatal chromosomal microarrays when performed for a fetus with structural abnormalities on ultrasound scan." Thesis, University of Birmingham, 2014. http://etheses.bham.ac.uk//id/eprint/4762/.
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Fetal chromosomes are examined conventionally by G-band karyotyping. More recently Prenatal Chromosomal Microarray (CMA) has been used to look for fetal chromosomal abnormalities. Advantages of CMA include its higher detection rate. Disadvantages include its detection of Variants of Unknown Significance (VOUS). I recruited a prospective cohort of 243 women with structural abnormalities on fetal ultrasound scan. A 1Mb targeted BAC array was performed in addition to G-band karyotyping. In 62 cases from this cohort an additional higher resolution 60K oligonucleotide array was used. A health economic analysis, by use of a decision tree, was performed. Finally qualitative work determined women’s feelings about testing. The 1Mb BAC cohort found a 4.1% increase in fetal chromosomal abnormalities over karyotyping, with a low detection rate of VOUS (0.4%). The 60K sub-cohort noted an extra 4.8% pathogenic chromosomal anomalies but, in addition, a 13% increase in VOUS. The health economic analysis indicated that when CMA is £360 (per test) and the Willingness To Pay (WTP) for a “positive diagnosis” is £9768; then CMA is cost effective over karyotyping. Qualitative analysis showed that couples were keen for as much information as possible. They struggled to recall and retain information conveyed at the time of the testing.
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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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Hughes, Katelyn. "Gene fusions in cancer: Classification of fusion events and regulation patterns of fusion pathway neighbors." Digital WPI, 2016. https://digitalcommons.wpi.edu/etd-theses/764.
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Cancer is a leading cause of death worldwide, resulting in an estimated 1.6 million mortalities and 600,000 new cases in the US alone in 2015. Gene fusions, hybrid genes formed from two originally separated genes, are known drivers of cancer. However, gene fusions have also been found in healthy cells due to routine errors in replication. This project aims to understand the role of gene fusion in cancer. Specifically, we seek to achieve two goals. First, we would like to develop a computational method that predicts if a gene fusion event is associated with the cancer or healthy sample. Second, we would like to use this information to determine and characterize molecular mechanisms behind the gene fusion events. Recent studies have attempted to address these problems, but without explicit consideration of the fact that there are overlapping fusion events in both cancer and healthy cells. Here, we address this problem using FUsion Enriched Learning of CANcer Mutations (FUELCAN), a semi-supervised model, which classifies all overlapping fusion events as unlabeled to start. The model is trained using the known cancer and healthy samples and tested using the unlabeled dataset. Unlabeled data is classified as associated with healthy or cancer samples and the top 20 data points are put back into the training set. The process continues until all have been appropriately classified. Three datasets were analyzed from Acute Lymphoblastic Leukemia (ALL), breast cancer and colorectal cancer. We obtained similar results for both supervised and semi-supervised classification. To improve our model, we assessed the functional landscape of gene fusion events and observed that the pathway neighbors of both gene fusion partners are differentially expressed in each cancer dataset. The significant neighbors are also shown to have direct connections to cancer pathways and functions, indicating that these gene fusions are important for cancer development. Future directions include applying the acquired transcriptomic knowledge to our machine learning algorithm, counting transcription factors and kinases within the gene fusion events and their neighbors and assessing the differences between upstream and downstream effects within the pathway neighbors.
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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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Freitas, Paula Curi de [UNESP]. "Análise citogenética e molecular do gene FOXO3 em síndrome mielodisplásica." Universidade Estadual Paulista (UNESP), 2011. http://hdl.handle.net/11449/92538.
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freitas_pc_me_sjrp.pdf: 528091 bytes, checksum: d630cd8e1a7a4fdc34c7e9200a36b8b5 (MD5)Síndromes Mielodisplásicas (SMD) compreendem um conjunto heterogêneo de doenças hematopoéticas caracterizadas por hematopoese ineficaz, que geralmente apresentam citopenias no sangue periférico, medula óssea hipercelular, diferenciação celular displásica e propensão ao desenvolvimento de leucemia mielóide aguda. São classificadas em oito tipos e a incidência anual é estimada entre dois e 12 casos por 100.000 pessoas da população em geral e em até 50 casos por 100.000 indivíduos com idades superiores a 60 anos. A análise cromossômica das células da medula óssea dos doentes ao diagnóstico detecta alterações diretamente relacionadas com o prognóstico em aproximadamente 50% dos casos. Alguns genes também foram relacionados à etiologia e prognóstico das mielodisplasias. O gene FOXO3, um supressor de tumor, embora não estudado anteriormente em SMD, é um dos genes que mais se expressam no tecido hematopoético normal. Alterações neste gene poderiam resultar em hematopoese anormal, pois já foram relacionadas a outros tipos de câncer, com mutações descritas no éxon 1. O objetivo deste trabalho foi estudar células da medula óssea de doentes com SMD de qualquer tipo, ao diagnóstico, para investigar a presença de alterações cromossômicas e de mutações no éxon 1 do FOXO3. A análise citogenética foi realizada em metáfases submetidas ao bandamento GTG, obtidas de culturas de curta duração de células da medula, sem estimulação mitogênica. Para a análise molecular foi extraído o DNA, realizada a amplificação gênica pela Reação em Cadeia da Polimerase e realizado o sequenciamento direto do éxon 1. Entre os 25 casos analisados, três (12%) apresentaram alterações cromossômicas clonais isoladas: deleção intersticial do braço longo do cromossomo 5; monossomia do cromossomo 21 e monossomia do cromossomo 22. Todas puderam ser relacionadas...
Myelodysplastic syndrome (MDS) constitute a heterogeneous group of hematopoietic diseases characterized by ineffective hematopoiesis usually with peripheral blood cytopenia, hypercellular bone marrow, dysplastic differentiation and a tendency to evolve to acute myeloid leukemia. They are classified in eight categories by the World Health Organization. The annual incidence is estimated at between two and 12 cases per 100,000 individuals in the general population and up to 50 cases per 100,000 of over 60-year olds. A chromosomal analysis of bone marrow cells at diagnosis identifies changes directly related to prognosis in approximately 50% of cases. Additionally, some genes are also associated to the etiology and prognosis of myelodysplasia. Although not previously studied in respect to MDS, a tumor suppressor, FOXO3, is one of the most commonly expressed genes in normal hematopoietic tissue. Changes in this gene could therefore result in abnormal hematopoiesis, as mutations described in exon 1 have already been associated with other types of cancer. The aim of this study was to investigate chromosomal alterations and mutations in exon 1 of FOXO3 in bone marrow cells from patients diagnosed with any type of MDS. Cytogenetic analysis was performed on metaphases submitted to GTG banding, obtained from short-term cultures of bone marrow cells without mitogenic stimulation. To evaluate mutations in the FOXO3 gene, DNA was extracted from the bone marrow, gene amplification was achieved by polymerase chain reaction and direct sequencing was performed. Of the 25 cases analyzed, three (12%) showed clonal chromosomal abnormalities in isolation characterized as the interstitial deletion of the long arm of chromosome 5, monosomy 21 and monosomy 22. All were correlated to the diagnosis and/or prognosis of patients. No mutations were detected in exon 1, but the 159C>T polymorphism was detected... (Complete abstract click electronic access below)
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Rodrigues, Rubens Matias. "Refinamento citogenético em indivíduos com anomalias craniofaciais sindômicas sem diagnóstico definido." Universidade de São Paulo, 2010. http://www.teses.usp.br/teses/disponiveis/61/61132/tde-17062010-141102/.
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Objetivos: Investigar possíveis alterações citogenéticas, através da técnica de bandamento de alta resolução, em indivíduos com anomalias craniofaciais associadas ao atraso no desenvolvimento neuropsicomotor e sem diagnóstico clínico-genético definido, com cariótipo (com bandas) prévio normal e estabelecer possível correlação entre o fenótipo dos indivíduos e as regiões cromossômicas alteradas. Local de execução: Laboratório de Citogenética Humana e Serviço de Genética Clínica, HRAC-USP, Bauru-SP. Indivíduos estudados e Resultados: O cariótipo de alta resolução de 16 indivíduos com anomalias craniofaciais associadas ao atraso no desenvolvimento neuropsicomotor pertencentes ao HRAC-USP, Bauru permitiu detectar alterações citogenéticas estruturais em 4 (25%) dos 16 indivíduos. Em 3 indivíduos detectou-se deleções em regiões subteloméricas (cromossomos 4p, 9p e 18q) e, em 1 indivíduo detectou-se adição de segmento cromossômico de origem desconhecida na região telomérica do cromossomo 12p. Conclusões: A frequência alta (25%) de alterações cromossômicas estruturais em regiões cromossômicas terminais (teloméricas e subteloméricas) mostra que a técnica de alta resolução é útil na identificação de alterações nessas regiões, portanto, indivíduos com anomalias craniofaciais e atraso mental, sem diagnóstico genético-clínico definido, cujo cariótipo convencional foi normal, devem ser, submetidos à análise dos cromossomos por meio do cariótipo de alta resolução antes do procedimento de CGHarray.Objective: To investigate possible cytogenetic abnormalities through high resolution banding technique in individuals with craniofacial anomalies presenting previous normal karyotype, associated to neuropsychological development delay, without clinic-genetic diagnoses, and establish possible correlation between phenotype and possible candidate chromosomal regions. Local: Human Cytogenetic Laboratory and Clinical Genetic Service, HRAC-USP, Bauru, SP. Individuals and Results: High resolution karyotype of 16 individuals with craniofacial anomalies associated to neuropsychological development delay in follow-up at the HRAC-USP, Bauru allowed the detection of structural chromosomal abnormalities in 4 (25%) of them. Three individuals presented deletion in the subtelomeric region (chromosomes 4p, 9p, and 18q), and one individual presented an addition of an unknown chromosomal fragment in the telomeric region of chromosome 12p. Conclusions: The high frequency (25%) of structural chromosomal abnormalities in terminal region (telomeric and subtelomeric) shows that the high resolution technique is useful for identification of structural anomalies in these regions. Therefore, individuals with craniofacial anomalies associated to neuropsychological development delay without a definitive clinic-genetic diagnoses presenting a normal conventional karyotype, should be submitted to chromosomal analysis through high resolution karyotype before CGH-array procedure.
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Lionetti, M. "BIOLOGICAL AND CLINICAL RELEVANCE OF MIRNA EXPRESSION SIGNATURES IN PRIMARY PLASMA CELL LEUKEMIA." Doctoral thesis, Università degli Studi di Milano, 2013. http://hdl.handle.net/2434/217172.
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Purpose: Plasma cell leukemia (PCL) is a very aggressive and rare hematological malignancy that can be distinguished into primary (pPCL), originating de novo, or secondary (sPCL), arising as a leukemic transformation of multiple myeloma (MM). Genomic and clinical differences between pPCL and MM have been demonstrated, mainly based on retrospective studies. This study was aimed at investigating the involvement of miRNAs in pPCL and their possible relationship with higher tumor aggressiveness.
Experimental design: MiRNA expression profiles were analyzed in highly-purified malignant plasma cells from 18 pPCL cases included in a prospective clinical trial. MiRNA expression patterns were evaluated in comparison with a representative series of multiple myeloma (MM) patients, in relation to the most recurrent chromosomal abnormalities (as assessed by fluorescence in situ hybridization and single nucleotide polymorphism-array analysis), and in association with clinical outcome. MiRNA expression was also integrated with gene expression profiles and computational prediction of miRNA target genes in pPCL and MM samples in order to identify putative target genes of deregulated miRNAs. The functional role of a few identified miRNAs in plasma cell dyscrasia pathogenesis was explored by transfection of synthetic pre/anti-miRNAs in multiple myeloma cell lines.
Results: We identified a series of deregulated miRNAs in pPCL (42 up- and 41 down-regulated) in comparison with MM. Some of them, based on their reported functions or putative target genes computed by integrative analysis, might have a role in the pathobiology of pPCL, such as miR-21, that was found to promote in vitro growth of MM cell lines. As regards chromosomal aberrations, the expression of some miRNAs mapped to hot-spot altered regions was associated with DNA copy number of the corresponding genomic loci; furthermore, TP53 deletion, a frequent cytogenetic lesion in our pPCL cohort, was found associated with a trend of down-regulation of miR-34a, whose tumor suppressor activity was demonstrated for the first time also in the context of MM. Finally, four miRNAs (miR-497, miR-106b, miR-181a* and miR-181b) were identified having expression levels correlated with treatment response, and four (miR-92a, miR-330-3p, miR-22, and miR-146a) with clinical outcome.
Conclusions: Overall, this study provides insights into the possible contribution of miRNAs in the pathogenesis of pPCL and suggests targets for future therapeutic investigations.
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Silva, Fernanda Borges da. "Uso do Single Nucleotide Polymorphism Array (SNP-A) na investigação de alterações citogenéticas em pacientes com síndromes mielodisplásicas." Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/17/17154/tde-29032017-164341/.
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As síndromes mielodisplásicas (SMD) constituem um grupo heterogêneo de doenças hematológicas de origem clonal, caracterizado por hematopoese ineficaz, citopenia e risco de evolução para leucemia mieloide aguda (LMA). As anormalidades citogenéticas adquiridas são marcadores prognósticos bem estabelecidos em SMD. No entanto, a técnica de citogenética metafásica apresenta limitações, incluindo baixa resolução e necessidade de divisão celular, sendo que defeitos cromossômicos podem não ser detectados. Tecnologias baseadas em microarranjo (array) de DNA, como o Single Nucleotide Polymorphism Array (SNP-A), são importantes para avaliação do genoma normal e neoplásico. O SNP-A foi desenvolvido para o estudo de todo o genoma, apresenta uma resolução superior a citogenética metafásica convencional, pode ser realizado em células na interfase, e detecta alterações cromossômicas não visualizadas pela citogenética metafásica. Além disso, o SNPA fornece dados de genotipagem para detecção de perda neutra de heterozigose, também denominada de dissomia uniparental somática. Regiões cromossômicas com deleção, perda neutra de heterozigose ou ganho são comuns em pacientes com neoplasias hematológicas e sugeriu genes candidatos a supressores de tumor e oncogenes. O objetivo do presente estudo foi a caracterização da coorte de pacientes com suspeita clínica de SMD e o uso integrado do método de citogenética convencional e SNP-A no serviço de hematologia da nossa instituição na investigação de alterações citogenéticas em pacientes com SMD e doenças relacionadas. Durante o período do estudo, foram recebidas um total de 114 amostras de pacientes com suspeita clínica de SMD. A análise clínica, morfológica e citogenética permitiu confirmar o diagnóstico de SMD ou doenças relacionadas em 43 pacientes (SMD [n=34], SMD/NMP [n=5], LMA com alterações mielodisplásicas [n=4]). Vinte e um pacientes foram classificados como citopenia idiopática de significado indeterminado (CISI) e 50 indivíduos apresentaram outros diagnósticos. SNP-A foi realizado em 17 pacientes com SMD e doenças relacionadas. Dentre os pacientes selecionados para o SNP-A, anormalidades cromossômicas foram observadas em 6/17 (35%) casos pelo cariótipo convencional e em 8/17 (47%) casos pela técnica de SNP-A. SNP-A não detectou quatro alterações cromossômicas previamente identificadas pela citogenética convencional: duas translocações balanceadas e duas alterações numéricas. SNP-A confirmou os demais achados identificados pela citogenética convencional e detectou um total de 32 novas lesões (1 ganho, 19 perdas e 12 UPDs) em 6 pacientes com SMD ou doenças relacionadas. SNP-A pode complementar a citogenética convencional na detecção de anormalidades cromossômicas em neoplasias mieloides.Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic diseases, characterized by inefficient hematopoiesis, peripheral blood cytopenias and a risk to progress to acute myeloid leukemia (AML). Acquired chromosomal abnormalities have prognostic value in MDS. However, metaphase cytogenetics has some limitations including low resolution and the requirement of cell division, and chromosomal abnormalities may not be detected. New technologies based on array, the Single Nucleotide Polymorphism Array (SNP-A), are able to evaluate the whole genome. The SNP-A has superior resolution compared to metaphase cytogenetics, may be used in interphase cells, and may detect chromosomal abnormalities not detected by metaphase cytogenetics. In addition, the SNP-A read-out includes genotyping calls and hybridization signal strength, corresponding to gene copy number, allowing detecting copy neutral loss of heterozigosity (CN-LOH), also known as uniparental dissomy (UPD). Deletions, copy neutral loss of heterozigosity or gain are frequent in patients with haematopoietic neoplasms and has already suggested the location of tumor suppressor genes and oncogenes. The aim of this study was to characterize the cohort of patients with clinical suspicion of MDS and to establish the integrative use of the conventional cytogenetic and the SNP-A in the investigation of chromosomal abnormalities in patients with MDS and related diseases followed at our institution. The clinical, morphological and cytogenetic evaluation allowed us to confirm the diagnosis of MDS or related disease in 43 patients (MDS [n=34], MDS/MPN [n=5], AML with myelodysplastic changes [n=4]). Twenty-one patients were diagnosed with idiopathic cytopenia with undetermined significance (ICUS) and 50 patients had other diagnosis. SNP-A were performed in 17 patients with MDS and related disease. Chromosomal abnormalities were observed in 6/17 (35%) cases by metaphase cytogenetics, and in 8/17 (47%) of the cases by SNP-A. SNP-A did not detected two balanced translocations and two numerical alterations previously observed by metaphase cytogenetics. SNP-A confirmed all the other findings observed by metaphase cytogenetics and SNP-A detected a total of 32 new lesions (1 gain, 19 losses and 12 UPDs) in 6 MDS and related diseases. SNP-A may complement metaphase cytogenetics to improve the detection of chromosomal abnormalities in myeloid neoplasms.
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Mohamed, Yousoof Saira Bahnu. "Genomic and functional approaches in identification and characterisation of novel eye disease genes." Thesis, The University of Sydney, 2013. http://hdl.handle.net/2123/10055.
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Donate, López Anna. "Efecte de l’edat paterna en les anomalies cromosòmiques numèriques i estructurals de l’espermatozoide humà." Doctoral thesis, Universitat Autònoma de Barcelona, 2016. http://hdl.handle.net/10803/400953.
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Aquesta tesi doctoral analitza la relació entre les anomalies cromosòmiques a l’espermatozoide i l'edat en homes de la població general. Els objectius principals d'aquest treball van ser determinar (1) la relació entre l'edat del donant i la freqüència i tipus d'anomalies cromosòmiques i (2) els cromosomes més implicats en les anomalies cromosòmiques a l'espermatozoide. Es va dur a terme la tècnica d’hibridació in situ fluorescent (FISH) als espermatozoides de 10 donants de la població general: 5 homes menors de 40 anys i 5 homes fèrtils majors o iguals a 60 anys. Es van analitzar 15.000 nuclis d’espermatozoides per a cada donant i 10.000 nuclis d’espermatozoides per a cada cromosoma en els 10 donants, amb FISH, fent servir el panel de sondes TelVysion, amb un total de 150.000 espermatozoides. Esta tècnica de FISH proporciona dades sobre la disomia en 19 cromosomes i d’anomalies estructurals en els 22 autosomes en una única mostra de semen per donant, reduint així al mínim la variabilitat intradonant i optimitzant al màxim l'anàlisi de FISH. Basant-nos en els resultats d’aquest treball, en els obtinguts prèviament i en les comparacions realitzades entre ells, podem concloure que: a) No hi ha diferències significatives en la incidència de disomia, diploïdia, ni en el total d’anomalies numèriques entre els donants més joves i els de més edat, b) L'aneuploïdia dels cromosomes sexuals és més comú que la dels autosomes i aquesta relació no canvia amb l'edat, c) Els nostres resultats suggereixen que algunes combinacions de sondes tenen una tendència a mostrar majors nivells de diploïdia, per tant, potencialment, poden afectar els resultats de FISH, augmentant les limitacions d’aquesta tècnica, d) Els individus de major edat mostren un increment en el percentatge d'anomalies estructurals (6,6%) en comparació amb els més joves (4,9%), e) La distribució de duplicacions i delecions no va ser lineal al llarg dels cromosomes, encara que es va observar una tendència cap a una freqüència més alta d’anomalies en els cromosomes més grans. Els nostres resultats demostren la presència d'un excés de duplicacions enfront de delecions en ambdós grups d’edat en una proporció de 2 a 1, f) Aquest treball és el primer estudi que aborda la freqüència d'anomalies cromosòmiques en l’espermatozoide de la majoria de cromosomes en un únic assaig fent així una contribució a l'aclariment de la quantitat i l'origen dels danys presents en els espermatozoides humans en relació amb l'edat.This doctoral thesis explores the relationship between sperm chromosome abnormalities and age in healthy men from the general population. The main objectives of this work were to determine (1) the relationship between donor age and frequency and type of chromosome abnormalities and (2) chromosomes more frequently involved in sperm chromosome abnormalities. We performed fluorescence in situ hybridization (FISH) in the spermatozoa of 10 donors: 5 men younger than 40 years old and 5 fertile men older than or equal to 60 years. We analyzed 15,000 sperm nuclei for each donor and 10,000 sperm nuclei for each chromosome in ten donors by FISH with a TelVysion assay, with a total of 150.000 sperm nuclei. This FISH technique provides data on disomy of 19 chromosomes and on structural abnormalities of 22 chromosomes in a single sperm sample per donor, thus minimizing intra-donor variability and optimizing consistent analysis. Based on our results, the results of the previous studies and the comparison between them, we must conclude that: a) There were no significant differences in the incidence of disomy, diploidy nor total numerical abnormalities between younger and older men, b) Aneuploidy of the sex chromosomes is more common than that of the autosomes, and the relationship between the two does not change with age, c) Our results suggest that some probe combinations have a tendency to show higher levels of diploidy thus potentially affecting FISH results and highlighting the limitations of FISH, d) Older patients had a higher rate of structural abnormalities (6.6%) compared with the younger men (4.9%), e) The distribution of duplications and deletions was not linear along the chromosomes, although a trend toward a higher rate of abnormalities in larger chromosomes was observed. Our findings demonstrate the presence of an excess of duplications versus deletions in both age groups at a ratio of 2 to 1, f) This work is the first study addressing the frequencies of sperm chromosome abnormalities of 19-22 chromosomes in a single assay thus making a contribution to the clarification of the amount and origin of damage present in human spermatozoa in relation to age.
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Abreu, Ludmila Serafim de. "Estudo Citogenético de Indivíduos Afetados por Deficiência Mental em Três APAES da Região de Ribeirão Preto." Universidade de São Paulo, 2010. http://www.teses.usp.br/teses/disponiveis/17/17135/tde-22042013-162950/.
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Em estudos etiológicos sobre a deficiência mental (DM), as anomalias cromossômicas, tanto numéricas quanto estruturais, são fatores que apresentam frequência relativa significante. O objetivo deste trabalho foi estudar as frequências e os tipos de anomalias cromossômicas em afetados por DM nas APAEs (Associação de Pais e Amigos dos Deficientes) de Batatais, Altinópolis e Serrana, objetivando conhecer melhor a contribuição destas anomalias na DM nessa região, caracterizando os tipos e as freqüências das aberrações cromossômicas observadas e compará-las entre as APAEs. Pacientes com suspeita de anomalias cromossômicas foram selecionados para o estudo. O critério usado para a seleção da amostra foi a realização do cariótipo em todos os afetados por DM com anomalias estruturais maiores e/ou menores. A análise citogenética foi feita através de cultura de linfócitos do sangue periférico e a coloração utilizada foi banda G, sendo analisadas 20 metáfases por paciente. Dos 505 indivíduos avaliados nas três APAES, 265 realizaram estudo citogenético, sendo encontradas 61 alterações cromossômicas (12,1% do total e 23,0% dos selecionados para cariótipo). Na APAE de Batatais, dos 305 indivíduos avaliados, 174 realizaram cariótipo, sendo encontradas 33 (10,8% do total) anomalias cromossômicas. Em Altinópolis, dos 107 indivíduos avaliados, 54 realizaram cariótipo, sendo observados 16 cariótipos anômalos (14,9% do total). Na APAE de Serrana, dos 93 indivíduos avaliados, 37 realizaram cariótipo, sendo encontradas 12 (12,9% do total) anomalias cromossômicas. Esses resultados demonstram que anomalias cromossômicas contribuem significativamente para a etiologia da DM e que a citogenética clássica possui importantes implicações na prática médica para o diagnóstico dos indivíduos afetados, assim como, para o aconselhamento genético das famílias. Além disso, observa-se que a APAE de Batatais, por apresentar uma porcentagem menor de indivíduos afetados por DM grave, 60,7%, possui uma menor incidência de anomalias cromossômicas quando comparada as APAEs de Altinópolis e Serrana que apresentam uma frequência de 87,8% e 83,9% de indivíduos com DM grave, respectivamente, indicando que alterações cromossômicas são mais frequentes em indivíduos afetados por DM grave.In etiological studies on mental retardation (MR), the chromosomal abnormalities, both numerical and structural, are factors that have significant relative frequencies. The objective was to study the frequencies and types of chromosomal abnormalities in patients affected by MR in APAEs (Associação de Pais e Amigos dos Deficientes) of Batatais, Altinópolis and Serrana. This aims to better understand the contribution of these abnormalities to MR in these regions, and thus characterizing the types and frequencies of chromosomal aberrations observed in order to compare them between APAEs. Patients suspected of chromosomal abnormalities were selected for the study. The criterion used for sample selection was the achievement of the karyotype of all patients affected by MR with major and/or minor structural abnormalities. Cytogenetic analysis was performed on cultures of peripheral blood lymphocytes, where the band G was used for staining. Twenty metaphases were analyzed per patient. Of the 505 individuals evaluated in three APAEs, a cytogenetic study was performed on 265 patients, and 61 chromosomal abnormalities were found (12.1% of the total and 23.0% of the selected karyotypes). In APAE of Batatais, karyotypes were performed on 174 of the 305 subjects studied, and we found 33 chromosomal abnormalities (10.8% of total). In Altinópolis, 54 karyotypes were performed out of the 107 subjects studied, and we observed 16 abnormal karyotypes (14.9% of total). In APAE Serrana, 37 karyotypes were performed out of the 93 subjects studied, and 12 chromosomal abnormalities (12.9% of total) were found. These results show that chromosomal abnormalities contribute significantly to the etiology of MR and that classical cytogenetics have important implications in medical practice for diagnosis of affected individuals as well as for genetic counseling of the families. Moreover, it is noted that in the APAE of Batatais, because of the smaller percentage of individuals affected by severe MR, 60.7% have a lower incidence of chromosomal abnormalities when compared to the APAEs of Altinópolis and Serrana which have frequencies of 87.8% and 83.9% of individuals with severe MR, respectively. This indicates that chromosomal abnormalities are more frequent in individuals affected by severe MR.
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Toyama, Julio Mitsutomo. "O papel da dopplervelocimetria do ducto venoso de 11 a 13 6/7 semanas no rastreamento de anomalias cromossômicas, malformações estruturais e prognóstico fetal." Universidade de São Paulo, 2004. http://www.teses.usp.br/teses/disponiveis/5/5139/tde-13102014-101232/.
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Objetivos: avaliar a contribuição do fluxo anormal no ducto venoso de 11 a 13 6/7 semanas no rastreamento de anomalias cromossômicas, defeitos estruturais e prognóstico gestacional. Método: 1221 gestações únicas foram submetidas a Dopplervelocimetria do ducto venoso após o rastreamento pela translucência nucal (TN). Resultados: os defeitos cromossômicos foram diagnosticados em 22 fetos. O fluxo no ducto venoso estava anormal em 84 fetos, a TN estava acima do 95o percentil em 160 casos e ambos marcadores estiveram anormais em 41 fetos. A sensibilidade, especificidade, valores preditivos positivo e negativo para defeitos cariotípicos corresponderam respectivamente a 86,4%, 86,9%, 11,9% e 99,7% considerando a TN aumentada, 68,2%, 96,9%, 31,3%, 99,3% para anomalias do fluxo do ducto venoso e 68,2%, 97,6%, 36,6%, 99,3% analisando ambos os marcadores. Investigando malformações estruturais, esses valores foram de 43,8%, 92,9%, 8,3%, 99,1% para uma TN aumentada, 25%, 92,6%, 4,8%, 98,8% para anomalias do fluxo do ducto venoso e 25%, 97,9%, 15,4%, 98,9% para ambos os marcadores. Nos casos com TN aumentada, a proporção de nascidos vivos morfológica e cariotipicamente normais diminui de 93,8% nos fetos com fluxo no ducto venoso normal para 77,3%, quando anormal. Conclusão: a avaliação do ducto venoso de 11 a 13 6/7 semanas de gestação pode ser utilizada no rastreamento de anomalias cromossômicas fetais e pode ajudar a reduzir a taxa de falso-positivo quando combinado com a medida da TN. Em fetos com TN aumentada o fluxo anormal no ducto venoso aumenta a probabilidade de resultados gestacionais adversosObjective: To evaluate the association between abnormal ductus venosus at 11 - 13 6/7 weeks\' gestation and chromosomal abnormalities, structural defects and fetal outcome. Methods: Ductus venosus waveform (DVFVW) and nuchal translucency (NT) thickness were prospectively evaluated in 1221 singleton pregnancies. Results: The DVFVW was abnormal in 84 cases, NT was above the 95th centile in 160 cases and both markers were observed in 41 fetuses. Chromosomal defects were diagnosed in 22 fetuses. The sensitivity, specificity and positive predictive values for an abnormal karyotype were respectively 86.4%, 86.9%, 11.9% for an increased NT; 68.2%, 96.9%, 31.3% for DVFVW abnormalities and 68.2%, 97.6%, 36.6% for both markers. Regarding structural defects, this values were 43.8%, 92.9%, 8.3% for an abnormal NT, 25%, 92.6%, 4.8% for DVFVW abnormalities and 25%, 97.9%, 15.4% for both. Considering those cases of unexplained fetal demise, the percentages were 44.4%, 85.9%, 5% for NT abnormalities, 22.2%, 92.6%, 4.8% for an abnormal DVFVW and 22.2%, 98%, 15.4% for both. In cases with increased NT measurement, the percentage of livebirths with normal karyotype and no major fetal structural defects decreased from 93.8% in normal DVFVW fetuses to 77.3%, when abnormal. Conclusion: Ductus venosus assessment at 11 - 13 6/7 weeks\' gestation is useful in screening for fetal chromosomal abnormalities and may help to reduce the false-positive rate when combining with NT thickness measurement. Abnormal DVFVW is also associated with an increase of adverse perinatal outcome in fetuses with enlarged NT. However, the value of DVFVW assessment in cases with normal NT measurement is unclear
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Freitas, Paula Curi de. "Análise citogenética e molecular do gene FOXO3 em síndrome mielodisplásica /." São José do Rio Preto : [s.n.], 2011. http://hdl.handle.net/11449/92538.
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Orientador: Agnes Cristina Fett ConteBanca: Cleide Largman Borovik
Banca: Cláudia Regina Bonini Domingos
Resumo: Síndromes Mielodisplásicas (SMD) compreendem um conjunto heterogêneo de doenças hematopoéticas caracterizadas por hematopoese ineficaz, que geralmente apresentam citopenias no sangue periférico, medula óssea hipercelular, diferenciação celular displásica e propensão ao desenvolvimento de leucemia mielóide aguda. São classificadas em oito tipos e a incidência anual é estimada entre dois e 12 casos por 100.000 pessoas da população em geral e em até 50 casos por 100.000 indivíduos com idades superiores a 60 anos. A análise cromossômica das células da medula óssea dos doentes ao diagnóstico detecta alterações diretamente relacionadas com o prognóstico em aproximadamente 50% dos casos. Alguns genes também foram relacionados à etiologia e prognóstico das mielodisplasias. O gene FOXO3, um supressor de tumor, embora não estudado anteriormente em SMD, é um dos genes que mais se expressam no tecido hematopoético normal. Alterações neste gene poderiam resultar em hematopoese anormal, pois já foram relacionadas a outros tipos de câncer, com mutações descritas no éxon 1. O objetivo deste trabalho foi estudar células da medula óssea de doentes com SMD de qualquer tipo, ao diagnóstico, para investigar a presença de alterações cromossômicas e de mutações no éxon 1 do FOXO3. A análise citogenética foi realizada em metáfases submetidas ao bandamento GTG, obtidas de culturas de curta duração de células da medula, sem estimulação mitogênica. Para a análise molecular foi extraído o DNA, realizada a amplificação gênica pela Reação em Cadeia da Polimerase e realizado o sequenciamento direto do éxon 1. Entre os 25 casos analisados, três (12%) apresentaram alterações cromossômicas clonais isoladas: deleção intersticial do braço longo do cromossomo 5; monossomia do cromossomo 21 e monossomia do cromossomo 22. Todas puderam ser relacionadas... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: Myelodysplastic syndrome (MDS) constitute a heterogeneous group of hematopoietic diseases characterized by ineffective hematopoiesis usually with peripheral blood cytopenia, hypercellular bone marrow, dysplastic differentiation and a tendency to evolve to acute myeloid leukemia. They are classified in eight categories by the World Health Organization. The annual incidence is estimated at between two and 12 cases per 100,000 individuals in the general population and up to 50 cases per 100,000 of over 60-year olds. A chromosomal analysis of bone marrow cells at diagnosis identifies changes directly related to prognosis in approximately 50% of cases. Additionally, some genes are also associated to the etiology and prognosis of myelodysplasia. Although not previously studied in respect to MDS, a tumor suppressor, FOXO3, is one of the most commonly expressed genes in normal hematopoietic tissue. Changes in this gene could therefore result in abnormal hematopoiesis, as mutations described in exon 1 have already been associated with other types of cancer. The aim of this study was to investigate chromosomal alterations and mutations in exon 1 of FOXO3 in bone marrow cells from patients diagnosed with any type of MDS. Cytogenetic analysis was performed on metaphases submitted to GTG banding, obtained from short-term cultures of bone marrow cells without mitogenic stimulation. To evaluate mutations in the FOXO3 gene, DNA was extracted from the bone marrow, gene amplification was achieved by polymerase chain reaction and direct sequencing was performed. Of the 25 cases analyzed, three (12%) showed clonal chromosomal abnormalities in isolation characterized as the interstitial deletion of the long arm of chromosome 5, monosomy 21 and monosomy 22. All were correlated to the diagnosis and/or prognosis of patients. No mutations were detected in exon 1, but the 159C>T polymorphism was detected... (Complete abstract click electronic access below)
Mestre
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Palle, Josefine. "Optimizing Chemotherapy in Childhood Acute Myeloid Leukemia." Doctoral thesis, Uppsala University, Department of Women's and Children's Health, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-9189.
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Despite major advances in our understanding of the biology of childhood acute myeloid leukemia (AML) and the development of new cytotoxic drugs, the prognosis of long-term survival is still only 60-65 %.
In the present research, we studied the pharmacokinetics of drugs used in the induction therapy of childhood AML and performed in vitro drug sensitivity testing of leukemic cells from children with AML.
The aims of the studies were to correlate the results of the analysis to biological and clinical parameters and to identify subgroups of AML with specific drug sensitivity profiles in order to better understand why treatment fails in some patients and how therapy may be improved.
Blood samples were analysed to study the pharmacokinetics of doxorubicin (n=41), etoposide (n=45) and 6-thioguanine (n=50). Doxorubicin plasma concentration and total body clearance were correlated to the effect of induction therapy, and doxorubicin plasma concentration was an independent factor for complete remission, both in univariate and multivariate analysis including sex, age, and white blood cell count at diagnosis. For etoposide and 6-thioguanine no correlation was found between pharmacokinetics and clinical effect. Children with Down syndrome (DS) tended to reach higher blood concentrations of etoposide and thioguanine nucleotides, indicating that dose reduction may be reasonable to reach the same drug exposure as in children without DS.
Leukemic cells from 201 children with newly diagnosed AML, 15 of whom had DS, were successfully analysed for in vitro drug sensitivity by the fluorometric microculture cytotoxicity assay (FMCA). We found that samples from children with DS were highly sensitive to most drugs used in AML treatment. In non-DS children, the t(9;11) samples were significantly more sensitive to cytarabine (p=0.03) and doxorubicin (p=0.035) than other samples. The findings might explain the very favorable outcome reported in children with DS and t(9;11)-positive AML. A specific drug resistance profile was found for several other genetic subgroups as well. A detailed study of MLL-rearranged leukemia showed that cellular drug sensitivity is correlated both to partner genes and cell lineage, findings that support the strategy of contemporary protocols to include high-dose cytarabine in the treatment of patients with MLL-rearrangement, both in AML and acute lymphoblastic leukemia (ALL).
Our results indicate that drug resistance and pharmacokinetic studies may yield important information regarding drug response in different sub-groups of childhood AML, helping us to optimize future chemotherapy in childhood AML.
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Ashton, Kevin John. "Genetic Aberrations in Non-Melanoma Skin Cancer." Thesis, Griffith University, 2002. http://hdl.handle.net/10072/367012.
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Genetic changes are hallmarks of cancer development involving the activation and/or inactivation of oncogenes and tumour suppressor genes, respectively. In non-melanoma skin cancer (NMSC) development, the initiation of genetic mutations results from exposure to solar ultraviolet radiation. Non-melanoma skin cancers are comprised of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Several related cutaneous lesions also exist, of which solar keratoses (SK) are widely accepted as a precursor dysplasia to SCC development. The study of recurrent genetic changes present within NMSC and SK should help reveal causative mutations in skin cancer development. Such analysis could also elucidate links in the genetic similarity of these dysplasia. The rapid screening of numerical changes in DNA sequence copy number throughout the entire genome has been made possible by the advent of comparative genomic hybridisation (CGH). This technique enables the identification of net gains and loss of genetic material within a tumour DNA sample. Chromosomal regions of recurrent gain or loss identify loci containing putative oncogenes and tumour suppressor genes, respectively with potential roles in NMSC tumourigenesis. Used in conjunction with tissue microdissection and universal degenerate PCR techniques this can enable the elucidation of aberrations in small histologically distinct regions of tumour. Such a technique can utilize archival material such as paraffin embedded tissue, which is the major source of neoplastic material available for cancer research. This study used the CGH technique to investigate aberrations in BCC, SCC and SK samples. The screening of copy number abnormalities (CNAs) in BCC revealed that although these tumours were close to diploid and generally genetically stable, they did contain several recurrent aberrations. The loss of genetic material at 9q was identified in a third of BCC tumours studied. This is characteristic of inactivation of the PTCH tumour suppressor gene, a known attribute in some sporadic BCC development. Validation of this loss was performed via loss of heterozygosity, demonstrating good concordance with the CGH data. In addition the over-representation of the 6p chromosome arm was revealed in 47% of biopsies. This novel CNA is also commonly observed in other cutaneous neoplasias, including Merkel cell carcinoma and malignant melanoma. This suggests a possible common mechanism in development and or promotion in these cutaneous dysplasias, the mechanisms of which have yet to be clearly defined. In contrast to BCC, numerical genetic aberrations in SCC and SK were much more frequent. Several regions of recurrent gain were commonly shared between both dysplasias including gain of 3q, 4p, 5p, 8q, 9q, 14q, 17p, 17q and 20q. Common chromosomal regions of loss included 3p, 8p, 9p, 11p, 13q and 17p. In addition loss of chromosome 18 was significantly observed in SCC in comparison to SK, a possible defining event in SK progression to SCC. The identification of shared genetic aberrations suggests a clonal and genetic relationship between the two lesions. This information further supports the notion for re-classification of SK to an SCC in situ or superficial SCC. Finally, the CNAs detected have been similarly observed in other squamous cell-derived tumours, for example cervical and head and neck SCC. This provides further evidence to common mechanisms involved in the initiation, development and progression of SCC neoplasia.
This study has identified a number of recurrent chromosomal regions, some of which are novel in NMSC development. The further delineation of these loci should provide additional evidence of their significance and degree of involvement in NMSC tumourigenesis. The identification of the cancer-causing genes mapped to these loci will further demarcate the genetic mechanisms of BCC and SCC progression. An understanding of the events involved in skin cancer formation and progression should shed additional light on molecular targets for diagnostics, management and therapeutic treatment.Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Health Sciences
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Souza, Daiane Corrêa de Souza e. "Estudo do padrão cromossômico em síndrome mielodisplásica primária hipocelular e sua correlação com aspectos celulares e clínicos." Universidade do Estado do Rio de Janeiro, 2009. http://www.bdtd.uerj.br/tde_busca/arquivo.php?codArquivo=1703.
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A SMD primária hipocelular ocorre com uma frequência de 10-20% dos casos de SMD no adulto, no entanto, é o subtipo mais frequente na infância. O diagnóstico da SMD primária hipocelular é bastante difícil, pois devido à ausência de células na medula óssea esta pode ser confundida com a LMA hipocelular ou AA. O diagnóstico diferencial entre estas entidades hematológicas é de extrema importância devido a maior agressividade da LMA e a possibilidade de evolução da SMD para LMA. Além disso, SMD e AA são indicadas para o TCTH, entretanto, o regime de condicionamento pré-transplante é específico para cada doença. A combinação entre a análise morfológica, realizada através do mielograma e biópsia de medula óssea, e análise citogenética tem desempenhado um papel fundamental no reconhecimento da SMD primária hipocelular. Entretanto, estudos têm sido realizados para tentar melhorar o diagnóstico da doença levando em consideração as características biológicas da SMD como a presença de apoptose. Sendo assim, este estudo teve como objetivo caracterizar o padrão cromossômico da SMD primária hipocelular e correlacionar com aspectos celulares e clínicos. Foram analisados citogeneticamente 86 casos de SMD primária hipocelular, 74 AR, 10 com AREB e 2 com AREB-t. Dentre os pacientes com AR 50% apresentaram cariótipo anormal e todos os pacientes com AREB e AREB-t apresentaram cariótipo anormal. A alteração cromossômica mais frequente foi a del(17p), seguida de alterações envolvendo o cromossomo 7. Nossos resultados sugerem que o padrão cromossômico em SMD primária hipocelular é caracterizado principalmente por perdas parciais e completas de cromossomos (deleções e monossomias). A análise citogenética auxiliou no diagnóstico dos casos com suspeita de SMD primária hipocelular e foi uma importante ferramenta para a escolha do tratamento. O IPSS mostrou ser um bom sistema de escala prognostica para este grupo de pacientes. Alterações envolvendo o cromossomo 17 estiveram associados com o subtipo AR e características displásicas envolvendo o setor granulocítico, no entanto, a del(17p) também pôde ser observada no subtipo AREB. Para análise de apoptose foram utilizadas 42 amostras de pacientes com SMD, 23 com SMD hipocelular, 8 com SMD normocelular e 11 com SMD hipercelular. O índice de apoptose total nos casos de SMD primária hipocelular apresentou uma média de 9,5%, enquanto os pacientes com SMD primária normocelular e hipercelular apresentaram uma média de 12% e 14,1%, respectivamente. Pela análise de linhagens específicas as células já comprometidas com o programa de diferenciação celular parecem ser o principal alvo do programa de apoptose. Apesar dos pacientes com SMD primária hipocelular apresentarem índice de apoptose total mais elevado que os controles eles foram sempre inferiores aos apresentados pela SMD primária normocelular e hipercelular, com exceção dos eritroblastos que foram maiores nos casos de SMD primária hipocelular. O índice de apoptose total foi maior nos estágios iniciais da doença independentemente da celularidade da medula óssea. Os pacientes com del (11q) e del (17p) estiveram associados com a diminuição do índice de apoptose total. Nossos resultados sugerem que a hipocelularidade da medula óssea não é causada pelo processo de apoptose e sim provavelmente por algum defeito no programa de proliferação celular.Hypocellular primary MDS occurs in a frequency of 10-20% of the adults MDS cases, however it is the most frequent subtype in childhood. Diagnosis of hypocellular primary MDS is very difficult, because the small number of cells in bone marrow and it can be confused with hypocellular AML or AA. The differential diagnosis between these hematologic entities is extremely important because of AML is more aggressive and the possibility of MDS evolve to AML. Besides, MDS and AA are indicated to HSCT, however, conditioning regimens before the transplantation is specific for each disease. The combination between morphologic analysis, carried out through mielogram and bone marrow biopsy, and cytogenetic analysis have been performed a fundamental role on the recognition of hypocellular primary MDS. However, studies have been carried out to try improving the MDS diagnosis considering the biological characteristics as the presence of apoptosis. Thus, the aim of this study was characterize the chromosomal pattern of hypocellular primary MDS and correlate with cellular and clinic aspects. It was analyzed 86 cases of hypocellular primary MDS, 74 RA, 10 RAEB and 2 RAEB-t. Patients with RA presented 50% of abnormal karyotype and all patients with RAEB presented abnormal karyotype as well as RAEB-t patients. The most frequent chromosomal alterations in this study was del(17p) followed by alterations involving chromosome 7. Our results suggest that chromosomal pattern in hypocellular primary MDS is characterized mainly by partial and complete loss of chromosomes (deletion and monosomy). The cytogenetic analysis aided in diagnosis of cases with suspicion of hypocellular primary MDS and it was an important tool for treatment choice. IPSS showed to be a good prognostic scoring system for this group of patients. Alterations involving chromosome 17 were associated with RA subtype and dysplastic characteristics involving granulocytic setor, however, we could see del(17p) in RAEB patients. For apoptosis analysis were used 42 samples of MDS patients, 23 with primary hypocellular MDS, 8 with primary normocelular MDS and 11 with primary hipercelular MDS. The total apoptosis index in cases of hypocellular primary MDS presented a average of 9,5%, whereas patients with primary normocelular MDS and primary hipercelular MDS presented an average of 12% and 14,1%, respectively. For the analysis of specific lineage cells already commited with cellular proliferation program appears to be the main target of apoptosis program. Despite of patients with primary hypocellular MDS presented total apoptosis index more raised than controls they were always lower than primary normocelular MDS and primary hipercelular MDS, except for eritroblasts that were higher in primary hypocellular. The total apoptosis index was higher in initial stage of the disease independently of the bone marrow cellularity. Patients with del(11q) and del(17p) were associated with decreasing of total apoptosis index. Our results suggest that the hypocellularity of bone marrow is not caused by apoptosis process, but probably by probably some defect in cellular proliferation program.
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Capizzi, Carmela. "Novel genomic technologies and molecular diagnostics in Colorectal Cancer." Doctoral thesis, Università di Catania, 2012. http://hdl.handle.net/10761/919.
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Cancer is a disease of the genome that is characterized by substantial variability in the clinical course and response to therapies. Colorectal cancer (CRC) is a heterogeneous cancer and represents an ideal model to investigate and elucidate the genetic alterations involved in tumor onset and progression. In this study 51 CRC patients were subdivided into groups according to the presence of microsatellite instability (MSI) and chromosomal instability (CIN). Of the 51 CRCs, 13.73% were MSI and 86.27% were microsatellite stable (MSS). The frequency of KRAS mutations in MSI-H and in MSS cancer was 28.57% and 40.91%, respectively.
To identify and characterize genomic alteration associated with colorectal cancer (CRC) the samples were analyzed with the last generation of Affymetrix single nucleotide polymorphism/CNV microarrays (SNP Array 6.0) and two new tools were implemented, Broad Cytogenetic Analysis (BroCyA) and Focal Cytogenetic Analysis (FoCyA), to identify broad (> ¼ chromosomal arm) and focal aberrations (< ¼ chromosomal arm). Broad copy number gains were noted on chromosomes 7, 8q, 9, 13q, 17q, 20 and broad copy number losses on chromosomes 4, 5q, 8p, 17p, 18, 19p, 20p and 22q. Moreover recurrent high level amplifications (HLAs) (copy number > 5.2) were located on chromosome 20, in regions containing known cancer pathway genes as STK4 and ID1, and homozygous deletions (HoD) containing potential new candidate tumor, suppressors such as BTG4 and D4S234E were located on chromosomes 11 and 4.
Recurrent somatic focal events (gains and losses) were identified in regions encompassing potential new candidate tumor suppressors and oncogenes, such as A2BP1 and PRDM16
Finally, several copy neutral-loss of heterozygosities (CN-LOHs) were detected, more frequently on chromosome 7p and 22q.
In conclusion, in this study some novel broad and focal copy number abnormalities (CNAs) and CN-LOHs were revealed in CRC. The precise and large-scale measurement of CNAs and CN-LOHs in the CRC genome provides a list of genes that might be involved in cancer development.
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Coultas, Susan L. (Susan Lynette). "A comparison of straight-stained, Q-stained, and reverse flourescent-stained cell lines for detection of fragile sites on the human X chromosome." Thesis, North Texas State University, 1985. https://digital.library.unt.edu/ark:/67531/metadc798127/.
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Cell cultures were examined for percentage of fragile sites seen in straight-stained, Q-stained and reverse fluorescent-stained preparations. In all cases, percentage of fragile site expression was decreased when compared to straight-stained preparations. However, fragile sites seen in Q- and RF-stain could be identified as on X chromosomes.
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Macdonald, Donald Hugh Charles. "Chromosome 13 abnormalities in myeloproliferative diseases." Thesis, Imperial College London, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.411308.
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Ben, Amor Hanene. "Chromosome abnormalities in preimplantation bovine embryos." Thesis, McGill University, 2004. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=111790.
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Note:Studies suggest that chromosomal abnormalities notably mosaicism consisting of normal and abnormal cells is a common feature observed in mammalian preimplantation embryos. The data on chromosome abnormalities in bovine embryos however, are limited. The principal aim of this study was to investigate chromosome abnormalities and their effect on the development of bovine embryos produced in vitro. 193 embryos were evaluated for chromosomal abnormalities, using dual fluorescent in situ hybridization (FISH) with developed DNA probes for X and Y chromosomes. Our results demonstrate that uniformly abnormal embryos were found mostly at the early cleavage stages, and embryos with extensive chromosome abnormalities were usually arrested by the morula stage. Chromosomal mosaicism was observed at the 2- cell stage and increased steadily with subsequent stages of development. By the blastocyst stage, chromosomal mosaicism was the main abnormality observed and affected 95% of the blastocysts. Most of the mosaic blastocysts comprised of diploid and tetraploid cells. In the second part, a detailed analysis of 121 day 7 and days 9-10 blastocysts, demonstrated that the proportion of polyploid cells in most of the morphologically good quality embryos was less than 15%, which was significantly lower than in poor quality embryos. [...]
II a ete suggere que des anomalies chromosomiques particulierement le mosaicism sont frequemment rencontres chez les embryons des bovins produit in vitro, cependant les donnees disponibles sont tres limitees. Le but principal de cette etude est d'evaluer les anomalies chromosomiques particulierement le mosaicism au different stades de developpement embryonnaire par FISH en utilisant des probes 'ADN pour les chromosomes X et Y. Nos resultats demontrent que des embryons uniformement anormales ont ete surtout trouves aux premiers stades de cleavage, temoignant que les embryons avec une vaste anomalie affectant la totalite des embryons sont souvent arretes au stade du morula. Le mosaicism chromosomique a ete rencontre dans tous les stades de developpement et il a augmente emarquablement pendant le developpement embryonnaire. Ainsi, au stade du blastocyst, le mosaicism chromosomique etait l'anomalie principale observee avec 95 % de blastocysts analyses devenant mosaiques. [...]
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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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Morris, Joanna Siriol. "Chromosome abnormalities in breast cancer cell lines." Thesis, University of Cambridge, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.627324.
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Hage, Mirella. "Mécanismes moléculaires impliqués dans la tumorigenèse et dans le comportement invasif des adénomes hypophysaires." Thesis, Université Paris-Saclay (ComUE), 2018. http://www.theses.fr/2018SACLS352.
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Résumé : Nous avons d’abord souhaité, dans ce travail de thèse, préciser les mécanismes moléculaires conduisant à l'expression ectopique du récepteur du GIP (glucose-dependent insulinotropic polypeptide receptor, GIPR) dans des adénomes somatotropes provenant de patients présentant une acromégalie avec une réponse paradoxale (stimulation) de l’hormone de croissance au glucose par voie orale. Nous avons montré que l’expression ectopique de GIPR se produit par une activation transcriptionnelle hypomorphe du gène GIPR associée à des anomalies de méthylation dans le corps du gène. L’activation de la voie AMP cyclique par le GIP postprandial dans les adénomes exprimant le GIPR peut représenter un mécanisme alternatif de la tumorigenèse somatotrope en l’absence de mutations de l’oncogène GNAS.Nous rapportons d’autre part une analyse cytogénétique approfondie des adénomes somatotropes, qui nous a permis de définir deux groupes d'adénomes, un groupe à faible altération du nombre de copies et un groupe à forte altération du nombre de copies. Deux tumeurs présentaient des réarrangements chromosomiques complexes avec une signature typique de chromothripsis, et une architecture sous-clonale incluant jusqu’à six populations cellulaires différentes, témoignant d’une hétérogénéité intratumorale importante.Dans une collection d'adénomes hypophysaires invasifs comportant la portion intrasellaire et la portion envahissante le sinus caverneux, nous avons montré par RNA-seq des profils d'expression génique divergents, apportant des arguments supplémentaires en faveur de l'hétérogénéité intratumorale dans ces tumeurs bénignes. Les échantillons tumoraux provenant de portions invasives ont montré une surexpression de la voie de transition épithélio-mésenchymateuse et des marqueurs de cellules souches cancéreuses soulignant leur rôle potentiel dans l’acquisition du phénotype invasif des cellules adénomateuses hypophysairesAbstractIn this work, we explored the molecular mechanisms of ectopic glucose-dependent insulinotropic polypeptide receptor (GIPR) expression in somatotroph adenomas from patients with acromegaly displaying a paradoxical GH increase to oral glucose. We showed that ectopic GIPR expression occurs through hypomorphic transcriptional activation of GIPR gene likely driven by DNA methylation changes. Activation of the cAMP pathway by postprandial GIP may represent an alternative tumorigenic mechanism in GIPR expressing somatotroph adenomas without driver mutations in GNAS oncogene. Cytogenetic profiling defined two groups of adenomas, a low-copy-number alteration (CNA) group and a high-CNA group.Two tumor samples displayed complex chromosomal rearrangements compatible with chromothripsis and showed subclonal architecture with up to six distinct cell population in each tumor, demonstrating an important intratumor heterogeneity.In a collection of invasive pituitary adenomas including the non-invasive intrasellar portions and the portions invading the cavernous sinuses, we showed by RNA-seq different gene expression profiles, providing supplemental evidence for the intratumoral heterogeneity in these benign tumors. Tumor samples from invasive portions showed up-regulation of the epithelial-mesenchymal transition pathway and increased expression of cancer stem-cell markers highlighting their potential role in pituitary tumor cell invasive behavior
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Ashton, Kevin John, and K. Ashton@griffith edu au. "Genetic Aberrations in Non-Melanoma Skin Cancer." Griffith University. School of Health Science, 2002. http://www4.gu.edu.au:8080/adt-root/public/adt-QGU20030818.122305.
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Genetic changes are hallmarks of cancer development involving the activation and/or inactivation of oncogenes and tumour suppressor genes, respectively. In non-melanoma skin cancer (NMSC) development, the initiation of genetic mutations results from exposure to solar ultraviolet radiation. Non-melanoma skin cancers are comprised of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Several related cutaneous lesions also exist, of which solar keratoses (SK) are widely accepted as a precursor dysplasia to SCC development. The study of recurrent genetic changes present within NMSC and SK should help reveal causative mutations in skin cancer development. Such analysis could also elucidate links in the genetic similarity of these dysplasia. The rapid screening of numerical changes in DNA sequence copy number throughout the entire genome has been made possible by the advent of comparative genomic hybridisation (CGH). This technique enables the identification of net gains and loss of genetic material within a tumour DNA sample. Chromosomal regions of recurrent gain or loss identify loci containing putative oncogenes and tumour suppressor genes, respectively with potential roles in NMSC tumourigenesis. Used in conjunction with tissue microdissection and universal degenerate PCR techniques this can enable the elucidation of aberrations in small histologically distinct regions of tumour. Such a technique can utilize archival material such as paraffin embedded tissue, which is the major source of neoplastic material available for cancer research. This study used the CGH technique to investigate aberrations in BCC, SCC and SK samples. The screening of copy number abnormalities (CNAs) in BCC revealed that although these tumours were close to diploid and generally genetically stable, they did contain several recurrent aberrations. The loss of genetic material at 9q was identified in a third of BCC tumours studied. This is characteristic of inactivation of the PTCH tumour suppressor gene, a known attribute in some sporadic BCC development. Validation of this loss was performed via loss of heterozygosity, demonstrating good concordance with the CGH data. In addition the over-representation of the 6p chromosome arm was revealed in 47% of biopsies. This novel CNA is also commonly observed in other cutaneous neoplasias, including Merkel cell carcinoma and malignant melanoma. This suggests a possible common mechanism in development and or promotion in these cutaneous dysplasias, the mechanisms of which have yet to be clearly defined. In contrast to BCC, numerical genetic aberrations in SCC and SK were much more frequent. Several regions of recurrent gain were commonly shared between both dysplasias including gain of 3q, 4p, 5p, 8q, 9q, 14q, 17p, 17q and 20q. Common chromosomal regions of loss included 3p, 8p, 9p, 11p, 13q and 17p. In addition loss of chromosome 18 was significantly observed in SCC in comparison to SK, a possible defining event in SK progression to SCC. The identification of shared genetic aberrations suggests a clonal and genetic relationship between the two lesions. This information further supports the notion for re-classification of SK to an SCC in situ or superficial SCC. Finally, the CNAs detected have been similarly observed in other squamous cell-derived tumours, for example cervical and head and neck SCC. This provides further evidence to common mechanisms involved in the initiation, development and progression of SCC neoplasia. This study has identified a number of recurrent chromosomal regions, some of which are novel in NMSC development. The further delineation of these loci should provide additional evidence of their significance and degree of involvement in NMSC tumourigenesis. The identification of the cancer-causing genes mapped to these loci will further demarcate the genetic mechanisms of BCC and SCC progression. An understanding of the events involved in skin cancer formation and progression should shed additional light on molecular targets for diagnostics, management and therapeutic treatment.
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Gonçalves, Rozana Oliveira. "Alterações genéticas em casais com antecedentes de aborto recorrente no primeiro trimestre da gestação." Centro de Pesquisas Gonçalo Moniz, 2013. https://www.arca.fiocruz.br/handle/icict/7640.
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Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil
O abortamento é considerado um problema multifatorial, cujas principais causas envolvidas na sua etiologia são os fatores ambientais (como exposição a substâncias tóxicas), genéticos, anatômicos, endócrinos, imunológicos, trombofílicos e doenças infecciosas (como toxoplasmose, rubéola). No entanto, os fatores genéticos são atribuídos principalmente aos abortamentos de primeiro trimestre da gestação. As alterações cromossômicas, o polimorfismo C677T, no gene da metilenotetrahidrofolato redutase (MTHFR677C>T); o polimorfismo G1691A, no gene do Fator V de Leiden (FVL1691G>A), e o polimorfismo G20210A, no gene da protrombina (PRT20210G>A), têm sido associados a problemas obstétricos, incluindo aborto recorrente. O objetivo deste trabalho foi investigar associação entre as mutações relacionadas à trombofilia, presença de alterações cromossômicas e a ocorrência de aborto espontâneo recorrente e avaliar possíveis interações entre as referidas mutações e as alterações cromossômicas. A casuística foi composta por 151 mulheres com história de aborto recorrente, 94 parceiros e 100 controles (mulheres sem histórico de aborto). A investigação das mutações foi realizada pela técnica de Reação em Cadeia da Polimerase- Polimorfismo de Tamanho de Fragmento de Restrição. As alterações cromossômicas foram investigadas pela cariotipagem com banda–G. A frequência das alterações cromossômicas foi de 7,3% nas mulheres com abortamento recorrente e 1% nos controles (p=0,022), e de 2,1% nos parceiros. No entanto, a frequência dos alelos MTHR677C>T (23% versus 22,5%), FVL1691G>A (1,5% versus 1% ) e PRT20210G>A (1,45% versus 0%) foi similar entre casos e controles, respectivamente. No grupo investigado, foi observada associação entre aborto recorrente e alterações cromossômicas, mas não foi encontrada associação com os polimorfismos gênicos investigados.
Abortion is considered a multifactorial problem, the most important causes involved in its etiology are, environmental factors ( as exposure to toxic chemicals), genetic, anatomic, endocrine, immunological, thrombophilic and infectious diseases (such as toxoplasmosis, rubella). However, genetic factors are mainly attributed to abortions of the first trimester of pregnancy. Chromosomal abnormalities, MTHFR 677C>T, factor V Leiden 1691G>A and prothrombin 20210G>A mutations have been associated with obstetric problems, including recurrent miscarriage. The objective of this research was to investigate associations between mutations in three genes commonly associated to thrombophilic events, chromosomal abnormalities and the occurrence of recurrent miscarriage. As well evaluate possible interactions between these mutations and chromosomal abnormalities. The sample was comprised of 151 women with history of recurrent miscarriages, 94 partners and 100 control (women with no history of abortion). The investigation of the mutations was performed by Polymerase Chain Reaction (PCR)/ Restriction Fragment Length Polymorphism (RFLP). Chromosomal aberrations were investigated by karyotyping with G-banda. The frequency of chromosomal abnormalities was 7.3% in women with recurrent miscarriage and 1% in controls (p = 0.022), and 2.1% in the partners. However, the frequency of allele MTHR677C> T (23% versus 22.5%), FVL1691G> A (1.5% vs. 1%) and PRT20210G> A (1.45% vs. 0%) was similar for cases and controls, respectively. In the investigated group was found association between recurrent miscarriage and chromosomal abnormalities, but no association was found with the genetic polymorphisms investigated.
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Zheng, Jianze. "Use of fluorescence in situ hybridization (FISH) for studying centromere organization and centric fusions in cattle." Title page, contents and abstract only, 1998. http://web4.library.adelaide.edu.au/theses/09A/09az63.pdf.
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Includes bibliograpical references (leaves 119-134). The most common chromosome abnormalities in live cattle are various Robertsonian translocations (centric fusions). Two hypotheses have been used to explain how monocentric Robersonian translocation chromosomes are generated: either direct formation, or evolution from dicentic chromosomes. Four main cattle procentric Satellite sequences were used as single and two-colour fluorescence in situ hybridization probes for studying the centromere organisation of cattle autosomes and the rearrangement in two cattle Robertsonian translocation chromosomes, the t(1:29) which is monocentric and found in numerous breeds, and the t(14:20) which is dicentric and found in 2 breeds.