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Genetische Variabilität in der phagozytären NAD(P)H-Oxidase: Funktionelle Charakterisierung und Bedeutung für die Zytostatika-Therapie / Genetic variability of phagocytic NAD(P)H oxidase: functional characterisation and impact on chemotherapyHoffmann, Marion 23 April 2008 (has links)
No description available.
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Exploring the Functional Relevance of Polymorphisms within the CD14 and IRF-1 Gene for Promoter Activity by Haplotype-Specific Chromatin Immunoprecipitation (HaploChIP)Mertens, Jasmin 19 January 2011 (has links)
No description available.
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Zytokinrezeptorpolymorphismen bei Patienten mit T-Non-Hodgkin-Lymphomen / Polymorphisms in cytokine receptor genes in patients with T-Non-Hodgkin-LymphomasStoller, Irene 09 February 2011 (has links)
No description available.
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PATTERNS OF NUCLEOTIDE VARIATION AND GENE-ASSOCIATED SNP ANALYSIS IN A QUERCUS spp. FOREST AT ISOCITRATE DEHYDROGENASE GENES / Muster der Nukleotid-Variation und Gen-assoziierte SNP-Analyse in einem Eichenbestand (Quercus spp.) an Isocitrat-Dehydrogenase GeneVidalis, Amaryllis 16 September 2010 (has links)
No description available.
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Développement de méthodes statistiques nécessaires à l'analyse de données génomiques : application à l'influence du polymorphisme génétique sur les caractéristiques cutanées individuelles et l'expression du vieillissement cutané.Bernard, Anne 20 December 2013 (has links) (PDF)
Les nouvelles technologies développées ces dernières années dans le domaine de la génétique ont permis de générer des bases de données de très grande dimension, en particulier de Single Nucleotide Polymorphisms (SNPs), ces bases étant souvent caractérisées par un nombre de variables largement supérieur au nombre d'individus. L'objectif de ce travail a été de développer des méthodes statistiques adaptées à ces jeux de données de grande dimension et permettant de sélectionner les variables les plus pertinentes au regard du problème biologique considéré. Dans la première partie de ce travail, un état de l'art présente différentes méthodes de sélection de variables non supervisées et supervisées pour 2 blocs de variables et plus. Dans la deuxième partie, deux nouvelles méthodes de sélection de variables non supervisées de type "sparse" sont proposées : la Group Sparse Principal Component Analysis (GSPCA) et l'Analyse des Correspondances Multiples sparse (ACM sparse). Vues comme des problèmes de régression avec une pénalisation group LASSO elles conduisent à la sélection de blocs de variables quantitatives et qualitatives, respectivement. La troisième partie est consacrée aux interactions entre SNPs et dans ce cadre, une méthode spécifique de détection d'interactions, la régression logique, est présentée. Enfin, la quatrième partie présente une application de ces méthodes sur un jeu de données réelles de SNPs afin d'étudier l'influence possible du polymorphisme génétique sur l'expression du vieillissement cutané au niveau du visage chez des femmes adultes. Les méthodes développées ont donné des résultats prometteurs répondant aux attentes des biologistes, et qui offrent de nouvelles perspectives de recherches intéressantes
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Déterminants biochimiques, génétiques et épigénétiques de l’encéphalomyélite myalgiqueChalder, Lynda 11 1900 (has links)
No description available.
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Analyse génomique de la coinfection par le virus VIH et VHC / Genomic analysis of HIV and HCV viruses during coinfectionUlveling, Damien 28 June 2016 (has links)
Plus de 170 millions d'individus sont infectés par le VHC dans le monde et 37 millions par le VIH. La coinfection VIH/VHC est fréquente et représente un élément clé de la prise en charge des patients infectés par le VIH. Depuis l'arrivée des HAART, les maladies du foie sont devenues la cause principale de mortalité chez les patients coinfectés VIH/VHC. L'évolution naturelle et le pronostic de l'hépatite C sont plus sévères en cas de coinfection par le VIH du fait d'une fibrose accélérée et d'une évolution rapide vers la cirrhose et ses complications. Certains facteurs accélérant la fibrose hépatique sont clairs aujourd'hui comme: l'absence de recours au traitement anti-VHC, la réplication active du VHC et la consommation excessive d'alcool. De plus, il existe de plus en plus de preuves que les variants génétiques contribuent à la fibrose hépatique chez les patients monoinfectés par le VHC, mais cet aspect a été peu étudié dans la coinfection VIH/VHC.Durant ma thèse, j'ai eu accès aux données d'un échantillon de 494 patients coinfectés génotypés issu de la cohorte ANRS CO13 HEPAVIH. L'histoire naturelle du VIH et du VHC y est renseignée de manière très détaillée et le suivi clinique des patients permet d'avoir des informations précises sur l'état de fibrose hépatique. J'ai pu alors réaliser deux études d'association « génome-entier » pour identifier des polymorphismes associés à la sévérité de la fibrose à l'aide de données complètes de 292 patients. La première étude a mis en évidence une association entre la quantification de l'élasticité hépatique par Fibroscan® et un locus, également répliqué dans la monoinfection par le VHC. Cette association a permis d'identifier deux gènes impliqués dans des mécanismes de maintien de structure et de signalisation cellulaire (CAV3) mais aussi dans la réplication du VHC (RAD18). La seconde étude a identifié deux associations significatives en comparant deux groupes de scores METAVIR (F0F1F2 vs F3F4), en particulier dans le gène CTNND2 qui est impliqué dans un réseau d'interaction associé à des mécanismes moléculaires lié à des maladies hépatiques.Ces deux études sont en cours de publication dans des revues scientifiques internationales à comité de lecture. Ces nouvelles perspectives dans la compréhension des mécanismes de fibrose dans le contexte de la coinfection VIH/VHC pourraient aider à l'identification de nouvelles cibles pour la création de médicaments ou de tests diagnostiques afin d'améliorer les soins des patients. / Over 170 million people worldwide are infected by HCV and 37 million by HIV. Both viruses share the same modes of transmission, and HIV/HCV coinfection is common and represents a key element in the management of patients infected with HIV. Since the appearance of HAART, liver diseases have become the leading cause of death in HIV/HCV coinfected patients. The natural history and prognosis of hepatitis C are more severe in case of coinfection with HIV due to accelerated rate of fibrosis progression and rapid progression to cirrhosis and its complications. Factors accelerating liver fibrosis are known today such as the lack of recourse to anti-HCV treatment, active HCV replication and excessive alcohol consumption. There is increasing evidence that genetic variants contribute to liver fibrosis in HCV monoinfection, but this aspect has been little studied in HIV/HCV coinfection.I have exploited the genotype information from 494 coinfected patients from the cohort ANRS CO13 HEPAVIH. These patients are very-well documented regarding the history of their HIV/HCV infection and are very carefully followed-up, especially regarding the status of liver fibrosis. I have performed two genome-wide association studies to identify polymorphisms associated with the severity of fibrosis from complete data of 292 patients. The first study has dealt with the quantification of liver stiffness by Fibroscan® and an association with the 3p25 region has been identified, also replicated in monoinfection HCV. Two genes involved in cell signaling and structure of holding mechanisms (CAV3) but also in HCV replication (RAD18) appear as good candidates. The second study has unraveled two significant associations by comparing the METAVIR score group (F0F1F2 vs F3F4), especially in the CTNND2 gene implicated in a network of interactions with molecular mechanisms involved in liver diseases.These results are under publications in peer-review international scientific journals. These new insights into the molecular mechanisms of liver fibrosis in patients with HIV/HCV co- infection may help to define new targets for drug development or new diagnostic tests, to improve patient care.
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Busca de variantes em sequência de DNA proveniente de pacientes com deficiência em processos de reparo do genoma / Identification of variants in the DNA sequence of patients deficient in DNA repair processesLivia Maria Silva Moura 08 October 2015 (has links)
Apesar de altamente estável, o DNA sofre milhares de alterações em sua estrutura diariamente, sejam essas espontâneas ou pela exposição a agentes mutagênicos. A maior parte dessas alterações é prontamente removida por um conjunto de eventos de reparo de DNA. A via de reparo por excisão de nucleotídeos (NER) é a mais versátil e flexível lidando com uma variedade de lesões que podem gerar distorções das hélices do DNA. Esses danos resultam em alterações características que, caso não reparadas, podem gerar mutações ou morte celular e, consequentemente, câncer e envelhecimento. Algumas síndromes, nas quais os pacientes são sensíveis à luz solar, estão relacionadas à deficiência no processo de NER, como a Xeroderma Pigmentosum (XP), síndrome de Cockayne (CS) e Tricotiodistrofia (TTD). Indivíduos brasileiros, incluindo pacientes com diagnóstico clínico de XP e membros das famílias, passaram por um processo in silico para a identificação variantes em genes relacionados aos processos de reparo do DNA após o sequenciamento do DNA por plataformas de nova geração (NGS: plataforma ABI 5500XL SOLiD e MiSeq Illumina) e análises de Bioinformática. Para cada paciente, foram selecionados os melhores valores de parâmetros para se realizar a busca por variantes considerando a qualidade de alinhamento e a taxa de cobertura das bases alvo. SNPs já depositados no banco de dados do projeto 1000genomes foram removidos de nossos dados. O restante das variantes foi analisado para encontrar potenciais candidatos que poderiam explicar o diagnóstico clínico do paciente. Em muitas amostras foi possível determinar pelo menos uma variante (mutação) com uma elevada possibilidade de ser responsável pelos sintomas XP. Para alguns pacientes, a má qualidade do sequenciamento ou eventos não esclarecidos durante este, dificultou a identificação de candidatos à mutação patogênica. Potenciais mutações não sinônimas foram analisadas com os programas SIFT e PROVEAN, que identificaram a potencial capacidade deletéria da alteração de aminoácido na proteína. Finalmente, foi desenvolvida uma interface de domínio público amigável, a Human Variantes do Finder Interface (http://www.varfinderhg.com.br), que visa facilitar a identificação de variantes em dados gerados por NGS. / Although highly stable, DNA molecule undergoes thousands of damage in its structure every day, due to spontaneous lesions or exposure to various mutagens. Most of these lesions are readily removed by a number of cellular DNA repair processes. The process of nucleotide excision repair (NER) is the most versatile and flexible dealing with a variety of lesions that can lead to distortions of the DNA strands. Ultraviolet irradiation induced DNA damage are the main substrates for NER. These DNA damage, if not repaired, can generate mutations or cell death causing several diseases, including cancer and aging. Some syndromes, sensitive to sunlight, are related to deficiencies in the NER process, such as Xeroderma Pigmentosum (XP), Cockayne syndrome (CS) and Trichothiodystrophy (TTD). Brazilian individuals, including patients with clinical diagnosis of XP and family members, went through in silico process for the identification of variants in genes related to DNA repair processes after DNA sequencing by next generation sequencing (NGS in the platforms ABI 5500XL SOLiD and MiSeq Illumina) and dedicated Bioinformatics pipelines. For each patient the best search pattern of variant calling was used considering the alignment quality and coverage rate of bases in target. SNPs already deposited at the 1000genomes project database were removed from the data. The remaining variants were analyzed to find potential candidates that could explain the clinical diagnosis. In many samples, it was possible to determine at least one variant (mutation) with a high possibility of being responsible for the clinical XP. For some patients, the poor quality of the sequencing or unclear events during sequencing hampered the identification of clear mutation candidates. Potential nonsynonymous mutations were analyzed with SIFT and PROVEAN softwares, which identified the potential deleterious capacity of the amino acid change in the protein. Finally, we developed a user-friendly public domain interface, the Human Variants Finder Interface (http://www.varfinderhg.com.br), which, we expect, will facilitate the identification of variants in data generated by NGS.
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Mapeamento de locos de resistência ao crestamento bacteriano comum do feijoeiro (Phaseolus vulgaris L.) / Genetic mapping of common bacterial blight resistance loci in common bean (Phaseolus vulgaris L.)Passos, Ana Laura Pereira 26 April 2016 (has links)
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Previous issue date: 2016-04-26 / Fundação de Amparo à Pesquisa do Estado de Goiás - FAPEG / The common bean (Phaseolus vulgaris) is grown in Brazil in various locations, soil and climatic
conditions. The diseases are among the leading causes of losses in productivity of this
legume, and the common bacterial blight (CBB) is the most important bacterioses that affects
the culture. The resistance of CBB in common bean is a complex quantitative trait that results
from the interaction of several genes. Genetic maps are tools that optimize the search for loci
associated with this type of feature, and the most commonly used molecular markers
available for this type of study are the SNPs (Single Nucleotide Polymorphism). In this sense,
this study aimed to: (i) develop a robust genetic map for common bean using SNP markers
and the RIL (Recombinant Inbreed Lines) mapping population derived from Ruda × AND 277;
(ii) characterize this RIL population and their parents about the reaction to common bacterial
blight in field and greenhouse; and (iii) identifying genomic regions (major genes and/or QTL)
that control the bacterial blight in this population. We used 393 individuals of the Ruda × AND
277 RIL population, evaluated for reaction to CBB in two field trials in Ponta Grossa - PR, in
the rain growing season of 2012 and 2014 and in an inoculation test at the greenhouse, in
Santo Antônio de Goiás - GO. The population was genotyped with 5,398 SNP markers and
mapping was performed using the R-OneMap and MapDisto programs. Statistical analyzes
were performed in the Genes program, and the Scott-Knott method was used for averages
groupingin R platform. The QTL analysis was conducted in QTLCartographer program. Using
the chi-square test (1:1), 2,062 markers were selected for mapping. Three genetic maps with
high strengt, saturation and resolution were built. Statistical analysis showed that there is
genetic variability for the CBB resistance in the population of RILs. The QTL analysis identified
10 QTLs linked to resistance of CBB in the Ruda × AND 277 RIL mapping population, in the
chromosomes PV01, PV02, Pv07, Pv09 and PV11, based on results from evaluations carried
out in the field and greenhouse. The maps constructed for this population have high strength
and resolution and may be used for future work on integrative mapping. The statistical
analysis evidenced the quantitative character of resistance to CBB in common bean and
showed that the parent Rudá has the CBB resistance alleles. It is expected that the markers
linked to these QTLs identified can be used in future studies of marker assisted selection. / O feijoeiro-comum (Phaseolus vulgaris) é cultivado no Brasil em vários locais e diversas
condições edafoclimáticas. As doenças estão entre as principais causas de prejuízos na
produtividade dessa leguminosa, sendo o crestamento bacteriano comum (CBC) a principal
bacteriose que afeta essa cultura. A resistência ao CBC no feijoeiro-comum é uma
característica complexa, quantitativa, que resulta da interação de vários genes. Os mapas
Genéticos são ferramentas que otimizam a busca de locos associados a esse tipo de
característica, e os marcadores moleculares mais utilizados disponíveis para esse tipo de
estudo são os SNPs (Single Nucleotide Polymorphism). Neste sentido, o presente trabalho
teve como objetivos: (i) construir um mapa genético robusto para o feijoeiro-comum,
utilizando marcadores SNP e a população de RILs (Recombinant Inbred Lines, ou linhagens
endogâmicas recombinantes) derivada do cruzamento Rudá × AND 277; (ii) caracterizar esta
população de RILs e seus genitores quanto à reação ao crestamento bacteriano comum, em
campo e em casa de vegetação; e (iii) identificar regiões genômicas (genes de efeito principal
e/ou QTLs) que controlam a reação ao crestamento bacteriano comum nesta população.
Foram utilizados 393 indivíduos da população de RILs Rudá × AND 277, avaliados quanto à
reação ao CBC em dois ensaios de campo em Ponta Grossa – PR, nas águas de 2012 e 2014,
e em um ensaio de inoculação em casa de vegetação, em Santo Antônio de Goiás - GO. A
população foi genotipada com 5.398 marcadores SNP e o mapeamento das RILs foi realizado
utilizando os programas R-OneMap e MapDisto. As análises estatísticas foram realizadas no
programa Genes, sendo o agrupamento de médias de Scott-knott realizado na plataforma R.
A análise de QTL foi realizada no programa QTLCartographer. Por meio do teste de quiquadrado
(1:1) foram selecionados 2.062 marcadores para o mapeamento. Foram construídos
três mapas genéticos com elevada robustez, saturação e resolução. As análises estatísticas
evidenciaram que há variabilidade genética para a característica de resistência ao CBC na
população de RILs. A análise de QTL identificou 10 QTLs ligados à resistência ao CBC na
população de RILs Rudá × AND 277 nos cromossomos Pv01, Pv02, Pv07, Pv09 e PV11 com
base em dados obtidos a partir de avaliações em campo e casa de vegetação. Os mapas
construídos para essa população apresentam elevada robustez e resolução e poderão ser
utilizados para futuros trabalhos de mapeamento integrativo. As análises estatísticas
evidenciaram o caráter quantitativo da resistência ao CBC em feijoeiro-comum e mostraram
que o genitor Rudá possui alelos de resistência ao CBC. Espera-se que os marcadores ligados
a esses QTLs identificados possam ser utilizados em futuros trabalhos de seleção assistida por
marcadores.
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Estudo genético de síndromes associadas à obesidade / Genetic studies of syndromes associated with obesityMauren Fernanda Moller dos Santos 27 May 2014 (has links)
A obesidade se tornou uma das maiores preocupações de saúde pública. É um distúrbio neuroendócrino, no qual fatores ambientais e genéticos agem em conjunto, levando ao excesso de armazenamento de energia na forma de gordura corporal. A síndrome de Prader-Willi (PWS) é a mais freqüente das síndromes que possui a obesidade como uma de suas características, com incidência de 1:25.000 nascimentos. É caracterizada por hipotonia neonatal com dificuldade de sucção, atraso do desenvolvimento neuropsicomotor (DNPM), hiperfagia, obesidade, baixa estatura em adolescentes, mãos e pés pequenos, hipogonadismo, distúrbios do sono, características faciais dismórficas, deficiência intelectual leve a moderada e comportamento obsessivo-compulsivo. Pacientes com atraso do DNPM e/ou dificuldade de aprendizado, distúrbios de comportamento, obesidade e/ou hiperfagia, com teste negativo para PWS, foram estudados com plataformas de SNP array, “The GeneChip® Mapping 500K Set” da Affymetrix, ou array-CGH, CytoSure ISCA 4x180k da OGT, para identificar genes relacionados a obesidade e hiperfagia, assim como, novas regiões genômicas implicadas na etiologia de síndromes genéticas associadas à obesidade. Dentre os 31 pacientes estudados, oito apresentaram variações de número de cópias (CNVs) em seu genoma: deleção em 1p22.1p21.2; deleção em 3q25.33q26.1 e deleção em 13q31.2q32.1; duplicação em 7q36.2; deleção em 8p23.3p23.1 e duplicação em 12p13.33p13.31; duplicação 16p13.11p12.3; duplicação em 17q11.2; deleção em 20p12.1; duplicação em 21q22.13. Duas dessas alterações foram herdadas de pais fenotipicamente normais. Algumas dessas CNVs sobrepõem regiões genômicas previamente relacionadas com obesidade, incluindo a microdeleção de 1p21.3 e as duplicações dos cromossomos 12 e 21. Identificamos genes anteriormente descritos como associados à obesidade (PTBP2, DPYD, MIR137, GNB3 e PPM1L), ou possivelmente envolvidos com este fenótipo (HTR5A e KCNJ6), mapeados em várias dessas CNVs. Além disso, os genes RNF135, NF1, DPP6, GPC5, DYRK1A e MACROD2 são os prováveis causadores da deficiência intelectual, atraso do desenvolvimento neuropsicomotor, dificuldades de aprendizagem, distúrbios de comportamento e outras características clínicas encontrados nos pacientes. O diagnóstico e prognóstico dos pacientes e o Aconselhamento Genético aos pais e familiares é fornecido / Obesity has become a major concern for public health. It is a neuroendocrine disorder, in which genetic and environmental factors act together, leading to excessive storage of energy as fat. Prader-Willi syndrome (PWS) is the main obesity-related syndrome with a birth incidence of 1:25,000. It is characterized by neonatal hypotonia, poor sucking, developmental delay, hyperphagia, obesity, short stature in adolescents, small hands and feet, hypogonadism, sleep disturbance, dysmorphic facial features, mild to moderate intellectual disability and obsessive-compulsive behavior. Patients with psychomotor developmental delay and/or learning disabilities, behavior disorders, obesity and/or hyperphagia, who tested negative for PWS, were studied by chromosomal microarray analysis, including the SNP-based platform “The GeneChip® Mapping 500K Set” (Affymetrix), and the array-CGH platform “CytoSure ISCA 4x180k (OGT)”, to identify genes related to hyperphagia and obesity, as well as new genomic regions implicated in the etiology of genetic syndromes associated with obesity. Of 31 patients studied, eight had copy number variants (CNVs) in the genome: 1p22.1p21.2 deletion; 3q25.33q26.1 deletion and 13q31.2q32.1 deletion; 7q36.2 duplication; 8p23.3p23.1 deletion and 12p13.33p13.31 duplication; 16p13.11p12.3 duplication; 17q11.2 duplicaton; 20p12.1 deletion; 21q22.13 duplication. Two of these CNVs were inherited from an unaffected father. Some of these CNVs overlap genomic regions that have previously been related to obesity, including the 1p21.3 microdeletion and the duplications of chromosomes 12 and 21. Furthermore, we identified genes previously described as associated with obesity (PTBP2, DPYD, MIR137, GNB3 and PPM1L), or possibly involved with this phenotype (HTR5A and KCNJ6), mapped to several of these CNVs. In addition, the genes RNF135, NF1, DPP6, GPC5, DYRK1A and MACROD2 are likely implicated in intellectual disability, developmental delay, learning disabilities, behavioral disorders and other clinical features found in patients. The diagnosis and prognosis of patients and genetic counseling to parents and families is provided
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