Made available in DSpace on 2015-03-03T11:52:24Z (GMT). No. of bitstreams: 0 Previous issue date: 2014-07-15Bitstream added on 2015-03-03T12:07:19Z : No. of bitstreams: 1 000810819.pdf: 308723 bytes, checksum: 524c7c0a9ecb8ecef63e198e5ccb23d3 (MD5) / A seleção genômica tem sido apontada como uma tecnologia que propiciará aumentos expressivos nas taxas de progresso genético em programas de melhoramento animal. Um dos fatores limitantes para a aplicação da seleção genômica é o custo associado à necessidade de genotipagem de um número grande de animais, com painéis de alta densidade, para a obtenção de boa habilidade de predição dos valores genéticos. Uma alternativa para reduzir custos seria genotipar parte dos animais com painéis menos densos e utilizar técnicas de imputação de genótipos. Em bovinos da raça Nelore, ainda não há consenso quanto à densidade dos painéis a serem utilizados e quanto à estratégia de genotipagem e imputação. Assim, objetivou-se com o presente projeto avaliar a habilidade de predição da seleção genômica utilizando painéis de marcadores moleculares de diferentes densidades, assim como o efeito da utilização de genótipos imputados na habilidade de predição da seleção genômica, em bovinos da raça Nelore. A característica considerada foi precocidade de terminação. Um total de 2035 animais geneticamente avaliados para essa característica e genotipados com o chip Ilumina ® HD Bovina (780k) foram utilizados nas análises, simulando uma situação em que os animais teriam sido genotipados com chips de densidade mais baixa. Análises de seleção genômica também foram executadas utilizando parte dos marcadores do painel de 780k , disponibilizando apenas os SNPs em comum com as seguintes painéis: Illumina® BovineLD (7K), Illumina® BovineSNP50 v2 (50K) e GeneSeek® Genomic Profiler 20K e 75K para Bos indicus. A imputação dos genótipos foi feita com o uso do programa FImpute e as predições genômicas foram conduzidas utilizando os métodos GBLUP e LASSO Bayesiano. Ambas análises, de imputação e de predição genômica, foram conduzidas de forma repetida, seguindo um esquema de validação cruzada, com a formação ... / Genomic selection has been considered as a technique that will allow significant increase in the genetic progress of animal breeding programs. A constrain for genomic selection application is the cost of genotyping several animals with high density chips in order to obtain a good prediction equation. An alternative to reduce costs is to genotype part of the animals with a lower density chip and to impute the unobserved genotypes. In Nelore cattle, there is no consensus about which chip and genotyping strategy should be adopted. Therefore, the aim of the present study was to evaluate the predictive ability of genomic selection in Nelore cattle using chips with different densities, and also to assess the effect of using imputed genotypes. The trait considered was finishing precocity. A total of 2,035 animals genetically evaluated for this trait and genotyped with the Illumina® Bovine HD chip (780K) were used in the analyses, mimicking a situation where the animals would have been genotyped with lower density chips. Genomic selection analyses were also run masking part of the 780K genotypes, making available just the SNPs in common with the following chips: Illumina® BovineLD (7K), Illumina® BovineSNP50 v2 (50K), GeneSeek® Genomic Profiler 20K and 75K for Bos indicus. Genomic prediction analyses were run with or without imputing the masked genotypes, using the software FImpute, and under the GBLUP and Bayesian LASSO methods. A 5- fold cross-validation scheme was adopted to perform the analyses, randomly assigning the groups. Results showed that the 50K and 75K chips presented the same predictive ability as the 780K chip. The results also indicated that if the 780K was considered as the target chip for applying genomic selection in the Nelore breed, its cost effectiveness could be improved with the strategy of genotyping part of the animals with a lower density chip (7K or 20K) and imputing their 780K missing genotypes. Further studies ...

abstract: Cancer is a heterogeneous disease with discrete oncogenic mechanisms. P53 mutation is the most common oncogenic mutation in many cancers including breast cancer. This dissertation focuses on fundamental genetic alterations enforced by p53 mutation as an indirect target. p53 mutation upregulates the mevalonate pathway genes altering cholesterol biosynthesis and prenylation. Prenylation, a lipid modification, is required for small GTPases signaling cascades. Project 1 demonstrates that prenylation inhibition can specifically target cells harboring p53 mutation resulting in reduced tumor proliferation and migration. Mutating p53 is associated with Ras and RhoA activation and statin prevents this activity by inhibiting prenylation. Ras-related pathway genes were selected from the transcriptomic analysis for evaluating correlation to statin sensitivity. A gene signature of seventeen genes and TP53 genotype (referred to as MPR signature) is generated to predict response to statins. MPR signature is validated through two datasets of drug screening in cell lines. As advancements in targeted gene modification are rising, the CRISPR-Cas9 technology has emerged as a new cancer therapeutic strategy. One of the important risk factors in gene therapy is the immune recognition of the exogenous therapeutic tool, resulting in obstruction of treatment and possibly serious health consequences. Project 2 describes a method development that can potentially improve the safety and efficacy of gene-targeting proteins. A cohort of 155 healthy individuals was screened for pre-existing B cell and T cell immune response to the S. pyogenes Cas9 protein. We detected antibodies against Cas9 in more than 10% of the healthy population and identified two immunodominant T cell epitopes of this protein. A de-immunized Cas9 that maintains the wild-type functionality was engineered by mutating the identified T cell epitopes. The gene signature and method described here have the potential to improve strategies for genome-driven tumor targeting. / Dissertation/Thesis / Doctoral Dissertation Chemistry 2017

Orientador: Luiz Francisco Zafalon / Coorientador: Fernando Antônio de Ávila / Coorientador: Oswaldo Durival Rossi Junior / Banca: Maurício de Alvarenga Mudadu / Banca: Luciano Menezes Ferreira / Banca: Hélio José Montassier / Banca: Marita Vedovelli Cardozo / Resumo: Tendo em vista a importância e o crescente interesse na produção de leite de búfala e seus derivados e da ocorrência de Staphylococcus coagulase negativa (SCN) como patógenos da mastite tanto em bovinos como em bubalinos. O presente estudo objetivou avaliar genes de virulência, a resistência a antimicrobianos, bem como metodologias para correta identificação destes SCN em ambiente de ordenha e no leite de bubalinos. Foram colhidas 320 amostras de leite de quartos mamários de 80 búfalas escolhidas aleatoriamente, 20 amostras de narinas e 20 amostras da boca dos bezerros bubalinos, 16 amostras das mãos dos ordenhadores e 64 amostras de insufladores das teteiras, coletadas durante a ordenha. Vinte e sete cepas de Staphylococcus coagulase negativa foram positivas para o gene eno, 10 para o gene ebps, 10 para o gene fnbA. Em relação aos genes relacionados com a produção de enterotoxinas, apenas uma cepa foi positiva para o gene sea, uma para o gene see e para os genes relacionados a resistência antimicrobiana, uma cepa foi positiva para o gene mecA. A identificação das espécies isoladas foi realizada utilizando-se a metodologia de MALDI-TOF MS e confirmada por iniciadores espécie-especifico desenhados neste estudo, exceto para S. agnetis o qual foi erroneamente identificado como S. hyiucs por espectofotometria de massa. Neste trabalho a identificação destas duas espécies foi confirmada por sequenciamento genômico de um isolado representativo. Foram observadas quatro amostras resis... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Due to the importance and the growing interest in buffalo milk production and its derivate and the concurrency of coagulase negative staphylococci as major mastitis pathogens both in cattle and in buffalo. This study aimed to search for virulence genes, antimicrobial resistance, and to evaluate methodologies for the identification of these microorganisms in samples of buffalo milk and from milking environment. For this, a total of 320 milk samples were collected from mammary quarters of 80 randomly selected buffaloes, 20 samples from nostrils and 20 samples from buffalo calves 'mouths, 16 samples from milking hands and 64 samples from liners were collected at the time of milking. Twenty-seven strains of coagulase negative staphylococci were positive for the eno gene, ten for ebpS gene, ten for the fnbA. Regarding genes related to enterotoxins production. Only one strain was positive for the sea and see gene and one for the mecA gene. The identification of the isolates was correctly done by MALDI-TOF MS and subsequently confirmed by species specific primers, except for S. agnetes that was wrongly identified as S. hyiucs. This identification was confirmed by genomic sequencing of a representative isolate from each species. There were four strains resistant to clindamycin, nine to vancomycin, one to chloramphenicol, seven to rifanmpicina, four to cefepime, seven to oxacillin, 17 to penicillin, 13 to erythromycin, 15 to cotrimoxazole and three to tetracycline. Furthermore, resistance to two or more antibiotics were observed in 21 isolates. The present study results may contribute to incidence prevention and control of mastitis in buffalo, caused by coagulase negative Staphylococcus. The main SCN species isolated were S. chromogenes, S. agnetis and S. epidermidis., the detection of genes related to adhesion and the production of enterotoxins m... (Complete abstract click electronic access below) / Doutor

Submitted by Flávia Regina Florencio de Athayde null (flavinhaflorencio@hotmail.com) on 2017-01-27T14:01:09Z No. of bitstreams: 1 Athayde_F_R_F_diss.mestrado.pdf: 1648129 bytes, checksum: a278e99a1cfea6cf938f7ec4bb928519 (MD5) / Approved for entry into archive by LUIZA DE MENEZES ROMANETTO (luizamenezes@reitoria.unesp.br) on 2017-01-31T13:33:23Z (GMT) No. of bitstreams: 1 athayde_frf_me_araca.pdf: 1648129 bytes, checksum: a278e99a1cfea6cf938f7ec4bb928519 (MD5) / Made available in DSpace on 2017-01-31T13:33:23Z (GMT). No. of bitstreams: 1 athayde_frf_me_araca.pdf: 1648129 bytes, checksum: a278e99a1cfea6cf938f7ec4bb928519 (MD5) Previous issue date: 2016-12-09 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Os protozoários do gênero Leishmania, da família Trypanosomatidae, são responsáveis por causar as leishmanioses, zoonoses de distribuição mundial que atingem países de regiões tropicais e subtropicais, representando um importante problema de saúde pública. As espécies de Leishmania patogênicas à humanos são classificadas em dois subgêneros, Leishmania e Viannia, sendo responsáveis pelas três formas clínicas mais comuns da doença. O subgênero Leishmania tem representantes no Velho e no Novo Mundo, enquanto que as espécies do subgênero Viannia estão presentes somente nas regiões tropicais das Américas, sendo responsáveis pela manifestação tegumentar na forma cutânea e mucocutânea. O avanço nas tecnologias de sequenciamento e montagem dos genomas de espécies de Leishmania têm possibilitado melhor entendimento das leishmanioses, da relação parasita-hospedeiro e até mesmo a identificação diferencial das espécies, auxiliando no entendimento das diferenças nas manifestações clínicas. Com o intuito de ampliar as informações genômicas das espécies de Leishmania e do subgênero Viannia, trabalhamos com o sequenciamento de DNA genômico e ferramentas de bioinformática para a montagem do genoma e anotação de proteínas de duas espécies, Leishmania (Viannia) guyanensis e Leishmania (Viannia) shawi. / The protozoa of the Trypanosomatidae family Leishmania genus, are responsible for causing leishmaniosis, zoonosis of global distribution that affects countries in tropical and subtropical regions, representing an important public health problem. The Leishmania species pathogenic to humans are classified into two subgenera, Leishmania and Viannia, which are responsible for three of the most common clinical manifestations of this disease. The subgenus Leishmania has representatives in the Old and New World, while the Viannia species are present only in the tropical regions of the Americas. These are responsible for the tegumentary manifestation of the cutaneous and mucocutaneous forms. The advance in the technologies of sequencing and the assembly of the genomes of Leishmania species have allowe to better understand the leishmaniosis, the parasite-host relationship and even the differential identification of the species thus, helping to understand the differences in the clinical manifestations. In order to expand the genomic information of the Leishmania species and the subgenus Viannia, we worked with genomic DNA sequencing and bioinformatics tools for assembling the genome and annotating proteins of two species, Leishmania (Viannia) guyanensis and Leishmania (Viannia) shawi.

Orientador: Danísio Prado Munari / Coorientador: Rodrigo Pelicioni Savegnago / Coorientador: Marcos Vinícius Gualberto Barbosa da Silva / Banca: Marcos Eli Buzanskas / Banca: Ana Fabrícia Braga Magalhães / Banca: Adriana Santana do Carmo / Banca: Fernando Sebastián Baldi Rey / Resumo: A implementação de dados de sequenciamento de nova geração - "next-generation sequence" (NGS) em programas de melhoramento genético animal representa a mais recente ferramenta na utilização de dados genotípicos nos modelos de associação genômica, tendo em vista que todo polimorfismo é considerado nas associações entre registros fenotípicos e dados de sequenciamento. Como em toda nova tecnologia, a prospecção das variantes ainda representa um desafio no sentido computacional e de viabilidade dos custos para sua implementação em larga escala. Diante desses desafios, neste trabalho buscou-se meios de explorar os benefícios na utilização da NGS nas predições genômicas e superar as limitações inerentes a esse processo. Registros fenotípicos e genotípicos (Illumina Bovine HD BeadChip) de 2.279 animais da raça Gir (Bos taurus indicus) foram disponibilizados pela Embrapa Gado de Leite (MG) e utilizados para as análises de associação genômica. Além disso, dados de sequenciamento de 53 animais do 1000 "Bulls Project" deram origem à população de referência de imputação. Visando verificar a eficiência de imputação, foram testados diferentes cenários quanto a sua acurácia de imputação por meio da análise "leave-one-out", utilizando apenas os dados de sequenciamento, que apresentaram eficiências de até 84%, no cenário com todos os 51 animais disponíveis após o controle de qualidade. Também foram verificadas as influências das variantes em baixa frequência na acurácia de imputação em difere... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: - Implementing "next-generation sequence" (NGS) data in animal breeding programs represents the latest tool in the use of genotypic data in genomic association models, since all polymorphisms are considered in the associations between phenotypic records and sequencing data. As with any new technology, variant prospecting still represents a computational and cost-effective challenge for large-scale implementation. Front to these challenges, this work sought ways to explore the benefits of using NGS in genomic predictions and overcome the inherent limitations of this process. Phenotypic and genotypic (Illumina Bovine HD BeadChip) records of 2,279 Gir animals (Bos taurus indicus) were made available by Embrapa Gado de Leite (MG) and used for genomic association analysis. In addition, sequence data of 53 animals from the 1000 Bulls Project gave rise to the imputation reference population. In order to verify the imputation efficiency, different scenarios were tested for their imputation accuracy through the leave-one-out analysis, using only the sequencing data, which presented efficiencies of up to 84%, in the scenario with all the 51 animals available after quality control. Influences from the low-frequency variants on the accuracy of imputation in different regions of the genome were also verified. After identifying the best reference population structure of imputation and applying the quality controls in the NGS and genomic data, it was possible to impute the 2 237 genotyped a... (Complete abstract click electronic access below) / Doutor

Genome Wide Association Studies (GWAS) have uncovered many genetic regions which are associated with autoimmune disease risk. In this thesis, I present methods which I have developed to build upon these studies and enable the analysis of the causal variants of these diseases. Colocalization methods disentangle whether potential causal variants are shared or distinct in related diseases, and enable the discovery of novel associations below the single-trait significance threshold. However, existing approaches require independent datasets to accomplish this. I extended two methods to allow for the shared-control design; one of these extensions also enables fine mapping in the case of shared variants. My analysis of four autoimmune diseases identified 90 regions associated with at least one disease, 33 of which were associated with 2 or more disorders; 14 of these had evidence of distinct causal variants. Once associated variants have been identified, we may wish to test some aggregate property, such as enrichment within an annotation of interest. However, the null distribution of GWAS signals showing association with a trait and preserving expected correlation due to linkage disequilibrium is complicated. I present an algorithm which computes the expected output of a GWAS, given any arbitrary definition of "null", and hence can be used to simulate the null distribution required for such a test. Commonly, GWAS report only summary data, and determining which genetic variants are causal is more difficult; the strongest signal may merely be correlated with the true causal variant. I have developed a statistical method for fine mapping a region, requiring only GWAS p-values and publicly available reference datasets. I sample from the space of potential causal models, rejecting those leading to expected summary data excessively different from that observed. This removes the need for the assumption of a single causal variant. In contrast to other summary statistic methods which allow for multiple causal variants, it does not depend upon availability of effect size estimates, or the allelic direction of effect and it can infer whether the pattern of association is likely caused by a non-genotyped SNP without requiring imputation. I discuss the effect of choice of reference dataset, and the implications for other summary statistics techniques.

Obesity and type-2 diabetes are major global health crises. The synthetic retinoid compound 4-hydroxy(phenyl)retinamide (Fenretinide, FEN), has been shown to inhibit adiposity and reverse insulin resistance in pre-clinical studies. Fenretinide acts via several different mechanisms, including induction of retinoid signalling and increased hepatic lipid oxidation to exert its metabolic effects. However, the signalling mechanisms behind these effects have yet to be fully elucidated. A number of approaches were taken in this thesis to investigate the signalling mechanisms of Fenretinide. To characterise the relationship between Fenretinide and leptin signalling, Fenretinide treatment was administered in two different leptin-deficient mouse models. Fenretinide effects on hepatic signalling mechanisms were further characterised by performing global transcriptomics analysis in liver from mice receiving HFD ± Fenretinide. In this analysis, the important metabolic hormone fibroblast growth factor (FGF) 21 was identified as a novel retinoid-dependent target of Fenretinide signalling, which was further characterised in multiple mouse models. Retinoic-acid receptor-specific ChIP-sequencing was performed in order to identify other liver genes that are regulated by Fenretinide via retinoid-dependent signalling mechanisms. This work has shown that the beneficial effects of Fenretinide on adiposity occur via a mechanism independent of that through which Fenretinide mediates effects on glucose homeostasis. Fenretinide effects on insulin sensitivity and glucose homeostasis are most likely mediated via the inhibition of ceramide synthesis in the liver and other metabolically active tissues. This work also shows that Fenretinide can normalise the effects of chronic HFD-feeding by targeting the expression of a set of PPARα-target genes in the liver via a retinoid-dependent signalling mechanism. Overall, the work described in this thesis both uncovers more detail about the signalling mechanisms of Fenretinide and identifies novel target genes that may be exploited for the development of new therapeutics to treat obesity and type 2 diabetes.

O advento do sequenciamento de nova geração (NGS - Next Generation Sequencing) nos últimos anos proporcionou um aumento expressivo no número de projetos genômicos. De maneira simplificada, as máquinas sequenciadoras geram como resultado fragmentos de DNA que são utilizados por programas montadores de genoma. Esses programas tentam juntar os fragmentos de DNA de modo a obter a representação completa da sequência genômica (por exemplo um cromossomo) da espécie sendo sequenciada. Em alguns casos o processo de montagem pode ser executado com maior facilidade para organismos com genomas de tamanhos pequenos (por exemplo bactérias com genoma em torno de 5Mpb), através de pipelines que automatizam a maior parte da tarefa. Um cenário mais complicado surge quando a espécie possui genoma com grande comprimento (acima de 1Gpb) e elementos repetidos, como no caso de alguns eucariotos. Nesses casos o resultado da montagem é geralmente composto por milhares de fragmentos (chamados de contigs), uma ordem de magnitude muito superior ao número de cromossomos estimado para um organismo (comumente da ordem de dois dígitos), dando origem a uma montagem altamente fragmentada. Uma atividade comum nesses projetos é a comparação da montagem com a de outro genoma como forma de validação e também para identificação de regiões conservadas entre os organismos. Embora o problema de alinhamento par-a-par de genomas grandes seja bem contornado por abordagens existentes, o alinhamento múltiplo (AM) de genomas grandes em estado fragmentado ainda é uma tarefa de difícil resolução, por demandar alto custo computacional e grande quantidade de tempo. Este trabalho consiste em uma metologia para fazer alinhamento múltiplo de genomas grandes de eucariotos com montagens altamente fragmentadas. Nossa implementação, baseada em alinhamento estrela, se mostrou capaz de fazer AM de grupos de montagens com diversos níveis de fragmentação. O maior deles, um conjunto de 5 genomas de répteis, levou 14 horas de processamento para fornecer um mapa de regiões conservadas entre as espécies. O algoritmo foi implementado em um software que batizamos de FROG (FRagment Overlap multiple Genome alignment), de código aberto e disponível sob licença GPLv3. / The advent of Next Generation Sequencing (NGS) in recent years has led to an expressive increase in the number of genomic projects. In a simplified way, sequencing machines generate DNA fragments that are used by genome assembler software. These programs try to merge the DNA fragments to obtain the complete representation of the genomic sequence (for example a chromosome) of the species being sequenced. In some cases the assembling process can be performed more easily for organisms with small-sized genomes (e.g. bacteria with a genome length of approximately 5Mpb) through pipelines that automate most of the task. A trickier scenario arises when the species has a very large genome (above 1Gbp) and complex elements, as in the case of some eukaryotes. In those cases the result of the assembly is usually composed of thousands of fragments (called contigs), an order of magnitude much higher than the number of chromosomes estimated for an organism (usually in the order two digits), giving rise to a highly fragmented assembly. A common activity in these projects is the comparison of the assembly with that of another genome as a form of validation and also to identify common elements between organisms. Although the problem of pairwise alignment of large genomes is well circumvented by existing approaches, multiple alignment of large genomes with highly fragmented assemblies remains a difficult task due to its time and computational requirements. This work consists of a methodology for doing multiple alignment of large eukaryotic genomes with highly fragmented assemblies, a problem that few solutions are able to cope with. Our star alignment-based implementation, was able to accomplish a MSA of groups of assemblies with different levels of fragmentation. The largest of them, a set of 5 reptilian genomes where the B. jararaca assembly (800,000 contigs, N50 of 3.1Kbp) was used as anchor, took 14 hours of execution time to provide a map of conserved regions among the participating species. The algorithm was implemented in a software named FROG (FRagment Overlap multiple Genome alignment), available under the General Public License v3 (GPLv3) terms.

Orientador: João Meidanis / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Computação / Made available in DSpace on 2018-08-11T06:12:01Z (GMT). No. of bitstreams: 1 Cogo_PatriciaPilisson_M.pdf: 1149626 bytes, checksum: 10816aa20a620eb105df492903697347 (MD5) Previous issue date: 2008 / Resumo: A evolução das técnicas de seqüenciamento tornou possível a obtenção de uma enorme quantidade de dados genômicos. O desafio atual é analisar esses dados e construir novos conhecimentos a partir deles. Neste contexto, um problema importante e ainda em aberto é a criação de métodos de análise taxonômica de genomas completos. Especialmente para organismos procariontes, para os quais ainda não há um conceito claro de espécie, a comparação de genomas completos pode significar uma importante contribuição. Neste trabalho propomos uma metodologia para comparação de genomas completos baseada na teoria de Rearranjo de Genomas, aplicando-a a organismos da família Vibrionaceae ¿ uma família heterogênea que compreende organismos de cinco diferentes gêneros, incluindo o vibrião causador da cólera, uma doença grave e que ainda causa anualmente milhares de mortes em países em desenvolvimento. As distâncias genômicas obtidas quando analisamos separadamente cada um dos dois cromossomos que compõem o genoma desses organismos estão de acordo com as árvores filogenéticas construídas empregando outros métodos de comparação genômica. Esse resultado corrobora nosso método e a utilização da teoria de rearranjo de genomas como uma alternativa para análise de genomas completos. Além disso, pode indicar que os eventos modelados neste trabalho, como perda de genes, transferências horizontais, reversões entre outros, exercem um papel importante na evolução desses organismos. Compreender a dinâmica desses eventos e combiná-la a outros métodos de análise genômica pode significar um grande avanço para a construção de uma filogenia mais acurada para estes vibriões / Abstract: The evolution in genomic sequencing techniques has resulted in a large amount of genomic data. The challenge that arises from this scenario is to analyze these data and to extract from them relevant biologic information. In this context, taxonomic analysis of complete genome sequences is still an open problem. Futhermore, it is critical for procaryotes, which still lack a clear definition of species, and whose taxonomic classification is in continuous evolution, where complete genomes comparison may well play a significant role. In this work, we propose a methodology to compare complete genomes based on genome rearrangement theory. We have applied our method to organisms of Vibrionaceae family ¿ a heterogeneous family that comprehends organisms from five different genera, including the agent responsible for cholera, a severe disease in developing countries. The genomic distances obtained when we analysed each chromosome individually are in agreement with phylogenic trees built using other genomic methods. This result validates our method and the genomic rearrangement theory as an alternative to analyze complete genomes. It also can indicate the importance played by rearrangement events in the vibrio genomic evolution. The understanding of these events, combined with other genomic methods, can play an important role in the construction of a robust vibrio phylogeny / Mestrado / Biologia Computaçional / Mestre em Ciência da Computação

Major Depressive Disorder (MDD) is a complex multifactorial disorder, which would lead to disability. Environmental and genetic factors are involved in MDD etiology. The aim of this project was to identify loci modifying age at onset (AAO) of MDD using survival models after adjusting for Childhood Sexual Abuse (CSA). To achieve this aim, a dataset was made available by the China Oxford and VCU Experimental Research on Genetic Epidemiology (CONVERGE) consortium. The study population had 5,220 controls and 5,282 cases with MDD. We performed two univariate association analyses using Cox Proportional Hazard (Cox PH) models. These two are Full Sample (FS), cases and controls, and only the Case Cohort (CC). No genome-wide significant associations were found in univariate analyses. Subsequent gene set enrichment analysis showed that there were significant enrichments in neurological Gene Ontology terms and some novel non-neural pathways. These findings may allow us to better understand MDD pathology.