Дисертації: "SNP candidati"

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Raschetti, M. "RICERCA E VALIDAZIONE DI SNP IN GENI CANDIDATI PER LA QUALITÀ DELLA CARNE E APPLICAZIONE DELL'ANALISI GENOMICA ALLA SPECIE SUINA." Doctoral thesis, Università degli Studi di Milano, 2010. http://hdl.handle.net/2434/150123.

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An important aim of pig selection in Italy is to obtain animals having a high aptitude for the PDO dry-cured ham production, such as Parma or S. Daniele ham. Over the past years, advances in the porcine genetic map have led to valuable gene and trait information being discovered. Since that time, sequences for the pig genome have been generated from various tissues, the sequencing of candidate genes, and more recently large scale genomic sequencing projects. These efforts are also being directed to SNPs identification for future large scale association studies. In the next years, the efficiency and accuracy of the traditional pig selection schemes could be improved by the implementation of molecular data into breeding programs. In this work, seven swine candidate genes for meat quality were investigated in order to identify informative SNPs. Molecular analyses were performed on twenty-two animals representing the extreme tails of the Gaussian distribution for three selected phenotypes (muscle compactness, fat thickness and the principal component 1) of 231 Large White x Landrace individuals. Among the nine identified SNPs, only two SNPs in the CRADD gene, two SNPs in the PTPRD gene and one SNP in the PIK3R2 gene showed a MAF (Minor Allele Frequency) more than 5% in the animals tested and therefore were considered for the subsequent association analysis. Association analysis between these five SNPs and the three phenotypes considered in this study was carried out using the GML procedure. The SNP CRADD g343 [A/G] showed a good association with the compactness of the muscles (P = 0,0498), the SNP PTPRD g30194 [G/T] showed a good association with the compactness of the muscles (P = 0,0195) and fat thickness dorsal (P = 0,0265), the SNP PIK3R2 g.3008 [C/T] showed a very good association with the compactness of muscle mass (P = 00,0014) and thickness of backfat (P = 0,0087). Therefore, the PIK3R2SNP g.3008 [C / T] was genotyped on all 231 animals of the population. The analysis showed a significant effect of this SNP on the following variables: marbling (P < 0.0001), fat cover (P < 0.05), fat thickness (P < 0.05), Prin1 (P < 0.05), Prin3 (P < 0.01); Prin4 (P < 0.01). In particular, the CC genotype was positively associated with marbling and fat cover. Moreover, the SNP in PIK3R2 gene was tested on 600 samples of three different Italian breeds (Large White, Duroc, Landrace) obtained from the National Association of Pig Breeders of Italy. Within each breed, the 100 individuals with the highest and the 100 individuals with the lowest values for EBVs (Estimated Breeding Values) for average daily weight gain were analyzed, resulting this SNP polymorphic in each breed. The association analyses between this SNP and these extreme EBVs showed a good association with backfat thikness, average daily gain, feed conversion rate and thigh weight in Landrace individuals. The two SNPs identified in CRADD gene and the two SNPs identified in the PTPRD gene were tested in another group of 560 Italian Large White animals with extreme EBVs for fat thickness. Three of the four SNPs resulted polymorphic also in this population. Then, association analysis between these three SNPs and EBVs for fat thickness were performed, showing the association of the SNP g29962[A/G ] of PTPRD gene with thigh weight. Another aim of this PhD thesis is the genetic characterization of a swine genetic type, the “Nero di Garlasco”, expressing both ancient and recent biodiversity. Although in the last years admirable efforts have been made to recover pig biodiversity, extremely endangered, today only few Italian local breeds can withstand the competition with commercial foreign breeds (i.e. the Large White, Landrace and Duroc) and with the commercial crosses today more and more widespread in the market. To date, at the national Herd Book only few breeds are registered as the Cinta senese, Mora Romagnola, Nero Siciliano, Casertana, Apulo-Calabrese and the Sarda. A very limited number with respect to the tens of breeds and lines cited in the textbooks of agronomy of the second postwar period. The majority of the extinct pig breeds were adapted to free range breeding, and were characterized by dark coat color (to defend themselves form the sun), slow growth and extensive fat deposits. In recent years, an ancient genetic type barely still existing (Razza di Garlasco) is reconstructing in the province of Pavia (Lomellina). In this case, pig phenotypes consisted of dark coat color and, surprisingly, high growth rates, similar to the commercial breeds. These two characteristics made these animals well adapted for the non-industrial production, where animals can be bred in free range, because the dark color protects them from the sun. To achieve this goal, a genetic characterization of the model population should be conducted. The tight bottleneck, through which this small population has passed, allows the fixation of genetic markers that enable precise traceability of the fresh and transformed products. This can give an added value to the breeding of theses animals that responds to the request for security and sustainability of the animal production system. Thanks to innovative technologies, a population of 96 animals, belonging to the Nero di Garlasco breed, was analyzed using the PorcineSNP60 BeadChip, in order to screen about 60,000 SNPs. The obtained data allowed a first description of the genetic structure of this population, but further studies are required to characterize this swine genetic type.

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Abou-Khater, Charbel. "Caractérisation de nouveaux gènes et polymorphismes potentiellement impliqués dans les interactions hôtes-pathogènes." Thesis, Aix-Marseille, 2017. http://www.theses.fr/2017AIXM0196/document.

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La coévolution ainsi que les différentes interactions entre hôte et pathogène contribuent à former la diversité génétique de ces deux organismes. Dans le cadre de cette thèse, nous nous sommes intéressés à l’étude de la variabilité génétique de 1760 gènes immunitaires choisis suivant des critères définis, pour essayer d’expliquer pourquoi il existe une variation individuelle face aux infections. L’objectif principal de ce projet était alors de caractériser et d'analyser de nouveaux gènes et polymorphismes immunitaires pouvant expliquer le contrôle ou la susceptibilité à certaines infections. Deux études pilotes nous ont permis de développer le pipeline de détection de polymorphismes. Pour la première, le polymorphisme des 3 gènes CD28, CTLA4, et ICOS a été caractérisé. Dans la deuxième, nous avons caractérisé le polymorphisme de 10 gènes impliqués dans la réponse immunitaire contre M. tuberculosis. Ces gènes ne sont pas très polymorphes et trois d’entre eux sont très conservés. Ces deux études nous ont aidés à préparer l’analyse à grande échelle avec les mises au point et l’amélioration du pipeline. Nous avons sélectionné 1760 gènes en se basant sur des critères définis. La variabilité génétique a été étudiée dans les populations humaines par une analyse minutieuse in silico de données de séquençage d’exomes générées par différents projets et consortiums pour plus de 700 individus représentant 20 populations à travers le monde. 30 gènes les plus polymorphes ont été ainsi identifiés. Ces gènes pourront être entièrement caractérisés et les données produites pourraient être comparées avec des données de résistance/sensibilité de certaines maladies infectieuses
Host-pathogen co-evolution and interactions contribute in shaping the genetic diversity of both organisms. The objective of this thesis is to define the genetic basis of variability in disease resistance/susceptibility through the development of large-scale in silico screens to identify novel gene candidates implicated in host-pathogen interactions (such as tuberculosis).A pilot study was conducted on CD28, CTLA4, and ICOS to investigate their polymorphism. As a first step in our study based on data available in the literature, we selected a set of ten genes relevant for the immune response against M. tuberculosis. Seven of these genes were moderately polymorphic, while three of them were highly conserved. This analysis was used to prepare and setup the large scale analysis using the same developed pipeline for polymorphism detection and allele reconstruction. For our in silico, we used sequence data from several projects and consortiums to isolate most polymorphic human genes amongst a list of over 1760 candidates selected based on already established relevance for infections and on evolutionary considerations. A first screen of 64 individuals from eight different populations from several regions of the world was performed and most variable genes were selected for further extensive analyses on a larger panel (715 individuals). 30 most polymorphic genes were thus identified. The extent of polymorphism and the allelic worldwide variants of each of these 30 genes are ready to be fully characterized. The data generated could be compared against infectious disease resistance/susceptibility data to identify potentially relevant gene variation

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Feuk, Lars. "SNP based strategies to study candidate genes for Alzheimer's disease /." Stockholm, 2002. http://diss.kib.ki.se/2002/91-7349-334-1.

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Lalagüe, Hadrien. "Genetic response of tree population to spatial climatic variation : an experimental genomic and simulation approach in Fagus sylvatica populations along altitudinal gradients." Thesis, Montpellier 2, 2013. http://www.theses.fr/2013MON20042/document.

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Un enjeu majeur de la génétique évolutive est de comprendre comment l'adaptation locale se développe en population naturelle, et comment les différentes forces évolutives y contribuent. Les études expérimentales d'adaptation locale utilisent couramment les gradients altitudinaux présentant une variation spatiale marquée des conditions environnementales. Dans ces conditions, on s'attend à ce que la différentiation génétique pour les caractères (traditionnellement mesurée par QST) et pour les gènes déterminant ces caractères (traditionnellement mesurée par FSTq) le long du gradient soit gouvernée de façon prédominante par la sélection et les flux de gènes, et peu influencée en revanche par la dérive génétique et la mutation. En particulier, des études théoriques ont montré un découplage entre QST et FST lorsque que les flux de gènes sont forts et/ou que la sélection est récente. Dans cette étude, nous avons testé cette hypothèse en combinant une approche de génomique expérimentale et des simulations dans des populations naturelles de hêtre commun (F. sylvatica) séparées de ~trois kilomètres et soumis à des environnements contrastés.Pour l'approche expérimentale, nous avons échantillonné 4 populations sur deux gradients altitudinaux sur le Mont Ventoux (avec une population à haute altitude et une à basse altitude sur chaque gradient). Cinquante huit gènes potentiellement impliqué dans la réponse aux stress abiotiques et dans le débourrement ont été séquencés sur un total de quatre-vingt seize individus, révélant 581 SNPs (Single Nucleotide Polymorphisms). Différentes approches ont été utilisées pour identifier les SNP outlier, présentant une différentiation plus forte qu'attendu sous un modèle neutre sans sélection. Le nombre de SNPs outlier identifié comme étant sous sélection s'est révélé être grandement dépendant de la méthode utilisé. La méthode fréquentiste a détecté de nombreux outliers alors que l'approche bayésienne n'a pu permettre de détecter des SNPs sous sélection. Par ailleurs, nous avons utilisé un modèle mécaniste individu-centré pour simuler les patrons de diversité phénotypique et génétique attendus le long du gradient pour la phénologie du débourrement végétatif, un caractère généralement adaptatif dans la réponse aux variations de température. Les résultats des simulations confirment que la différentiation génétique observée pour le caractère (QST) est généralement plus forte que celle observée au gène (FSTq), et que cette différentiation génétique au trait intervient dès la première génération. Toutefois, les tests d'outlier conduits sur le le modèle simulé ont révélé que plus de 95% des SNPs outlier sont des faux positifs. Comme dans l'approche expérimentale, l'approche Bayésienne ne s'est pas révélé suffisamment fiable pour détecter des QTLs dans des populations spatialement proche et génétiquement faiblement différentiée. Néanmoins une approche multi-locus basée sur un estimateur peu utilisé en génétique (le Zg) a révélé la forte corrélation inter-populations inter-gènes des QTLs confirmant les attendus théoriques. Toutefois, cette approche ne permet pas de détecter précisément les QTLs sans connaissance a priori sur les QTLs. En conclusion, les travaux de cette thèse mettent en évidence la rapidité des changements génétique qui interviennent en moins de 5 générations pendant la modification du climat, et la difficulté de détecter les gènes codant pour des traits complexes
A major challenge in population genetics is to understand the local adaptation process in natural population and so to disentangle the various evolution forces contributing to local adaptation. The experimental studies on local adaption generally resort to altitudinal gradients that are characterized by strong environmental changes across short spatial scales. Under such condition, the genetic differentiation of the functional trait (measured by the Qst) as well as the genes coding for trait (measured by Fstq) are expected to be mainly driven by selection and gene flow. Genetic drift and mutation are expected to have minor effect. Theoretic studies showed a decoupling between Qst and Fst under strong gene flow and / or recent selection. In this study, I tested this hypothesis by combining experimental and modelling genomic approach in natural population of Fagus sylvatica separated by ~3 kilometres and under contrasted environments.Sampling was conducted in south-eastern France, a region known to have been recently colonised by F.sylvatica. Four naturally-originated populations were sampled at both high and low elevations along two altitudinal gradients. Populations along the altitudinal gradients are expected to be subjected to contrasting climatic conditions. Fifty eight candidate genes were chosen from a databank of 35,000 ESTs according to their putative functional roles in response to drought, cold stress and leaf phenology and sequenced for 96 individuals from four populations that revealed 581 SNPs. Classical tests of departure of site frequency spectra from expectation and outlier detection tests that accounted for the complex demographic history of the populations were used. In contrast with the mono-locus tests, an approach for detecting selection at the multi-locus scale have been tested.The results from experimental approaches were highly contrasted according the method highlighting the limits of those method for population loosely differentiated and spatially close. The modelling approach confirmed the results from the experimental data but revealed that up to 95% of the SNPs detected as outliers were false positive. The multi-locus approach revealed that the markers coding for the trait are differentially correlated compared to the neutral SNPs. But this approach failed to detect accurately the markers coding for the trait if no a priori knowledge is known about them. The modelling approach revealed that genetic changes may occur across very few generation. But while this genetic adaptation is measurable at the trait level, the available method for detecting genetic adaptation at the molecular level appeared to be greatly inaccurate. However, the multi-locus approach provided much more promise for understanding the genetic basis of local adaptation from standing genetic variation of forest trees in response to climate change

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Costa, ?rica Cristina Xisto da. "Polimorfismo do gene MSTN e do SNP BIEC2-808543 e sua rela??o com crescimento de potros da ra?a brasileiro de hipismo." Universidade Federal Rural do Rio de Janeiro, 2015. https://tede.ufrrj.br/jspui/handle/jspui/1392.

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The gene encoding myostatin (MSTN), located on chromosome 18 (ECA 18) and the SNP BIEC2-808543 located in the intergenic region, which precedes the gene encoding the protein similar to the nuclear corepressor receptor dependent binder (LCORL), located on chromosome 3 (ACE 3) in horses, both positioned in regions that are associated with conformational traits of these animals. In view of this, we aimed to identify if the variations described in MSTN and LCORL loci exist in the study population; and to identify the effects of these polymorphisms on the growth profiles of these animals. For this purpose, the characteristics measured were weight, height at withers and hip height of foals at different ages, belonging to the Coudelaria e Campo de Instru??o de Rinc?o do Ex?rcito Brasileiro. Nonlinear mixed models were adjusted resulting from the combination of six nonlinear simple models, Brody (1945), Gompertz (Winsor, 1932), Logistics (Ratkowski, 1983), Von Bertalanffy (1957), generalized Michaelis- Menten (Lopez et al., 2000) and Richards (1959) associated with four types of variance functions for each model, homogeneous, exponential, asymptotic and staggered. The polymorphism described in the promoter region of the MSTN gene was not found in the studied population, in which there has been only the T allele, however the BIEC2-808543 polymorphism, located in the region prior to the LCORL gene is significantly associated (P <0, 05) to the characteristics evaluated, in which the animals who presented the genotype TT were smaller and lighter when compared to the other genotypes. There was no significant difference between animals with CT and CC genotype. The model that best describes the growth curve for body mass variance is the model of Brody (1945) associated with the scaled variance for the variable height at the withers the model that best fit was the Von Bertalanffy (1957) (adjusted without polymorphism effect in b) parameter associated with the asymptotic variance and the characteristic hip height the model that best described was that of Brody (1945) associated with the asymptotic variance, explaining that the nonlinear mixed models are indeed promising to describe equine growth curves, for the simple models did not differ much among themselves what defined in fact the selection of the model was the variance, being for body mass staggered variance and the height at the withers and on the back, the asymptotic variance. This polymorphism can be used as molecular markers for early selection of foals as to the characteristics evaluated
O gene que codifica a miostatina (MSTN), localizado no cromossomo 18 (ECA 18) e o SNP BIEC2-808543 localizado na regi?o interg?nica que antecede o gene que codifica a prote?na semelhante a correpressor de receptor nuclear dependente de ligante (LCORL), localizado no cromossomo 3 (ECA 3) de cavalos, ambos posicionados em regi?es que est?o associadas ?s caracter?sticas conformacionais destes animais. Diante disto, objetivamos identificar se as varia??es descritas nos loci MSTN e LCORL, existem na popula??o em estudo; al?m de verificar os efeitos desses polimorfismos sobre os perfis de crescimento desses animais. Com este intuito foram mensuradas as caracter?sticas massa corporal, altura na cernelha e altura na garupa de potros em diversas faixas et?rias, pertencentes ? Coudelaria e Campo de Instru??o de Rinc?o do Ex?rcito Brasileiro. Foram ajustados modelos n?o lineares mistos que resultaram da combina??o de seis modelos n?o lineares simples, Brody (1945), Gompertz (Winsor, 1932), Log?stico (Ratkowski, 1983), Von Bertalanffy (1957), Michaelis-Menten generalizado (L?pez et al., 2000) e Richards (1959), associados a quatro tipos de fun??es de vari?ncia para cada modelo, homog?nea, exponencial, assint?tica e escalonada. O polimorfismo descrito na regi?o promotora do gene MSTN n?o foi encontrado na popula??o estudada, na qual observa-se apenas o alelo T, entretanto o polimorfismo BIEC2-808543, localizado na regi?o que antecede o gene LCORL, est? significativamente associado (P<0,05) ?s caracter?sticas avaliadas, sendo os animais que apresentaram o gen?tipo TT menores e mais leves quando comparado com os demais gen?tipos. N?o foi observada diferen?a significativa entre os animais com gen?tipo TC e CC. O modelo que melhor descreve a curva de crescimento para a vari?vel massa corporal ? o modelo de Brody (1945) associado com a vari?ncia escalonada, para a vari?vel altura na cernelha o modelo que melhor se ajustou foi o de Von Bertalanffy (1957) (ajustado sem efeito de polimorfismo no par?metro b) associado com a vari?ncia assint?tica e para a caracter?stica altura na garupa o modelo que melhor a descreveu foi o de Brody (1945) associado ? vari?ncia assint?tica, elucidando que os modelos n?o-lineares mistos s?o de fato promissores para a descri??o de curvas de crescimento de equinos, pois os modelos simples n?o diferiram muito entre si o que definiu de fato a sele??o do modelo foi a vari?ncia, sendo para massa corporal a vari?ncia escalonada e para as alturas, na cernelha e na garupa, a vari?ncia assint?tica. Este polimorfismo pode ser utilizado como marcador molecular para sele??o precoce de potros quanto ?s caracter?sticas avaliadas

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Alves, Fernanda Aparecida Vargas de Brito e. "ANÁLISE DO POLIMORFISMO T102C DO RECEPTOR DE SEROTONINA (HTR2A) EM PACIENTES COM FIBROMIALGIA E CONTROLES." Pontifícia Universidade Católica de Goiás, 2012. http://localhost:8080/tede/handle/tede/2360.

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Introduction: Fibromyalgia is a syndrome characterized by widespread chronic pain. The syndrome is chronic with dubious possibility of healing. The prevalence in the world population varies from 0,66 to 4,4 %. It is believed that fibromyalgia is the result of abnormal changes in sensory processing of pain. In this context, are inserted gene polymorphisms T102C gene HTR2A serotonin receptor. The HTR2A gene T102C polymorphism is the presence of a thymine (T) or cytosine (C), defined by a transition from T to C at nucleotide position 102. It is a silent polymorphism receptor gene HTR2A, which determine the different levels of gene expression. Objectives: To determine and compare the allele frequency and genotype of the T102C polymorphism of the serotonin receptor gene HTR2A in a group of 48 women diagnosed with fibromyalgia and 50 healthy controls. Methodology: For this we used the PCR- RFLP , from DNA extracted from peripheral blood samples obtained from control and testing. The comparison of allele and genotype frequencies was performed by Chi -square test. Results: The results showed allele frequencies obtained for both groups were: T (46,9%) and C (53,1%). The TT genotype frequencies were found (22,9%), TC (47,9%) and CC (29,2%) for patients with fibromyalgia and TT (16%), TC (70%) and CC (14%) for controls. Conclusions: The FMS is composed of multiple characteristics that reflect a diversity of causes. Our results showed a significantly higher frequency for the CC genotype in patients with FMS, partially explaining the reduced serotoninergic response observed in such patients.
Introdução: A Fibromialgia é uma síndrome reumática caracterizada por dor difusa e crônica. A síndrome é crônica com duvidosa possibilidade de cura. A prevalência na população mundial varia de 0,66 a 4,4%. Acredita-se que a fibromialgia seja o resultado de mudanças anormais no processamento sensorial da dor. Neste contexto, inserem-se os polimorfismos do gene T102C do gene do receptor de serotonina HTR2A. O polimorfismo T102C do gene HTR2A consiste na presença de uma timina (T) ou citosina (C), definida por uma transição de um T para C na posição nucleotídica 102. Trata-se de um polimorfismo silencioso do gene do receptor HTR2A, que determinam níveis de expressão gênica diferentes. Objetivos: Determinar e comparar a freqüência alélica e genotípica do polimorfismo T102C do gene do receptor de serotonina HTR2A em um grupo de 48 mulheres diagnosticadas com fibromialgia e 50 controles saudáveis. Metodologia: Para isso foi utilizada a técnica de PCR-RFLP, a partir de DNA extraído de amostras de sangue periférico obtidas do grupo controle e testes. A comparação das freqüências alélicas e genotípicas foi feita por meio de teste Chi-quadrado. Resultados: Os resultados demonstraram as freqüências alélicas obtidas para os dois grupos foram: T (46,9%) e C (53,1%). As freqüências genotípicas encontradas foram TT (22,9%); TC (47,9%) e CC (29,2%) para os pacientes com fibromialgia e TT (16%); TC (70%) e CC (14%) para os controles. Conclusões: A SFM é composta por múltiplas características que refletem em uma diversidade de causas. Nossos resultados demonstraram que o genótipo CC foi significativamente mais comum nas pacientes com a SFM, justificando parcialmente a menor resposta serotononérgica observada nesse grupo.

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Donatoni, Flavia Aline Bressani. "Prospecção de SNPs por eletroforese capilar e sua identificação em genes candidatos relacionados à resistência de caprinos a nematóides gastrintestinais." Universidade de São Paulo, 2012. http://www.teses.usp.br/teses/disponiveis/75/75135/tde-24072012-163708/.

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Citocinas são pequenas moléculas de sinalização celular que desempenham um papel muito importante no sistema imunológico e atuam na comunicação intracelular. Escolheu-se cinco genes pertencentes a essa família com o objetivo de se estudar SNPs que possam estar associados com a resistência à verminose gastrintestinal em caprinos. São eles: IL2, IL4, IL13, IFNg e TNFa. Para isso foi estudada uma população de 229 caprinos. Estes animais foram produzidos na Embrapa Caprinos e Ovinos (Sobral, CE) a partir de animais das Raças Saanen, raça considerada susceptível a endoparasitas gastrintestinais e Anglo-nubiana, raça considerada resistente aos mesmos endoparasitas. Após dois cruzamentos a terceira geração de animais, considerada F2, possuía 229 animais. Foram coletadas amostras de sangue para posteriores etapas de extração de DNA e quantificação; foram coletadas também amostras de fezes para contagem de ovos por grama de fezes (OPG). Os dados foram transformados em log10(n+1), onde n é número de ovos por grama de fezes, e analisados usando o procedimento dos modelos mistos do SAS (2002/2003). Os efeitos fixos incluídos no modelo foram sexo, coleta e idade a coleta e a variável animal foi utilizada como efeito aleatório. Com base no resultado dessa análise escolheu-se 44 animais com fenótipos extremos para resistência. Visando a prospecção de SNPs foram sequenciadas duas regiões do gene IL2, uma região do gene IL4, duas regiões do gene IL13, três regiões do gene IFNg e quatro regiões do gene TNFa. Foram encontrados dois SNPs no gene IL2 (intron 1 e intron 2), um SNP no gene IL4 (intron 3), um SNP no gene IL13 (intron 1), seis SNPs no gene IFNg (dois no exon 1, um no intron 1, um no intron 2, um no exon 3 e um no exon 4) e dez SNPs no gene TNFa (dois deles na região promotora do gene, dois no intron 2 e seis no exon 4). Verificou-se que há alteração de aminoácido na sequência de apenas um dos SNPs encontrados em regiões codificadoras de proteínas. A troca ocorre no segundo SNP localizado no exon 1 do gene IFNg (A/C), onde há alteração do aminoácido asparagina (considerando o alelo A) para treonina (alelo C). O estudo da associação entre as amostras extremos para resistência e os marcadores tipo SNP foi realizado com o teste de Fisher e observou-se que, dentre os vinte SNPs encontrados, oito deles apresentaram um valor de P ≤0,05, o que indica que os SNPs são potenciais marcadores moleculadores para resistência à verminose gastrintestinal, ou seja, provavelmente associados ao fenótipo estudado. Para essa associação ser validada é necessário estudar o efeito desses SNPs na população completa e em outras populações.
The cytokines are small cell-signaling proteins that play important role in immunologic system acting in intracellular communication. Five genes from cytokine family, i.e., IL2, IL4, IL13, IFNg, and TNFa were selected to search for SNPs, which may be associated with goat gastrointestinal endoparasites resistance. A population of 229 goats was produced in Embrapa Caprinos (Sobral, CE, Brazil). This population was an F2 offspring from a F1 intercross, which was in turn produced by crossing Saanen pure breed considered to be susceptible to gastrointestinal endoparasites with Anglo-nubiana pure breed considered to be resistant. Blood samples were collected for DNA extraction and fecal samples were collected for parasite egg counting. The data were transformed in log10(n+1), where n is the number of eggs per gram of feces, and analyzed by using the mixed model procedure of SAS (2002/2003). The fixed effects included were sex, sampling and age at sampling. The animal variable was used as random effect. After data analyses, forty four phenotypic extremes for endoparasite resistance were selected. Two regions of the gene IL2, one region of each gene IL4 and IL13, three regions of IFNg, and four regions of TNFa were sequenced in the search for SNPs. Two SNPs were found in the gene IL2 (intron 1 and intron 2), one SNP was found in IL4 (intron 3) one SNP in IL13 (intron 1) six SNPs in IFNg (two in the exon 1, one in the intron 1, one in the intron 2, one in the exon 3, and one in the exon 4) and ten SNPs were found in the gene TNFa (two in the promoter region, two in the intron 2 and six in the exon 4). Among all the SNPs found within exons only the second SNP of the IFNg exon 1 changes the amino acid. This SNP replaces an asparagine (allele A) by a threonin (allele C). The association study between the extremes and SNPs was performed using the Fisher exact test. A number of eight of the twenty described SNPs presented significant P value (P ≤0.05) indicating association with gastrointestinal endoparasite resistance and thus, the potential applicability as molecular markers for genetic improvement efforts involving this disease. To validate the associations, however, is necessary to study the effect of SNPs in a great number of animals and also in a variety of breeds.

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Carolino, Maria Inês Alves de Carvalho Martins. "Influências genéticas nas características da carcaça e carne em bovinos." Doctoral thesis, Universidade de Lisboa. Faculdade de Medicina Veterinária, 2015. http://hdl.handle.net/10400.5/11653.

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Tese de Doutoramento em Ciências Veterinárias - Especialidade de Produção Animal
A seleção das características da carcaça e da qualidade da carne, que são normalmente avaliadas post-mortem, é complicada, pelo que a utilização de marcadores moleculares pode constituir uma estratégia alternativa no melhoramento genético animal. Neste trabalho utilizaram-se 273 amostras de bovinos de 9 raças/populações provenientes do Brasil (Angus, Holstein, Simental, cruzados Pardo Suíço x Holstein, Montana, cruzados Guzerá x Holstein, Gir, Nelore e Tabapuã) e de 211 amostras de animais das raças Blanc Bleu Belge (BBB), Alentejana e Mertolenga explorados em Portugal, com o objetivo de proceder à sua caracterização genética em 20 SNP’s (CAPN316, CAPN530, CAPN4751, CAPN4753, CAPN5331, CAST257, CAST2959, LEP140, LEP252, LEP305, UASMS1, UASMS2, UASMS3, nt414, nt419, Q204X, E226X, nt821, E291X, C313Y) pertencentes aos genes da calpaína, calpastatina, leptina e miostatina. As frequências genotípicas e alélicas dos SNP’s localizados nos genes codificadores da calpaína (μ-calpaína) e calpastatina mostraram distribuições muito semelhantes às encontradas por outros autores. No gene da Leptina, as diferenças observadas entre os animais provenientes do Brasil e de Portugal, sugere que estes grupos de animais têm influências genéticas distintas (Bos indicus e Bos taurus) e que, possivelmente, possam ter sido sujeitos a processos de seleção diferentes. Na raça Mertolenga o genótipo ++ do SNP nt821 do GDF8 está associado com melhores valores genéticos para a capacidade maternal, capacidade de crescimento e longevidade produtiva, mas com piores valores genéticos para o intervalo entre parto. Os resultados obtidos demonstraram que há um efeito da congelação nas características físicas da carne (cor, força de corte, capacidade de retenção de água e pH). A tenrura da carne é influenciada pelos genótipos dos marcadores CAPN316, CAPN4751, CAST2 e LEP140, com diferenças máximas do valor da FC de 2,35Kgf, 4,96Kgf, 5,24kgF, e 9,04Kgf, respetivamente. O marcador UASMS3 tem influência na percentagem de AGM trans da carne de animais da raça Alentejana, enquanto os marcadores CAPN530 e LEP252 têm influência na percentagem de AGS C16:0 e AGCL n3 da carne de animais da raça Mertolenga. Os resultados obtidos confirmam a utilidade dos marcadores estudados no melhoramento genético e que as raças bovinas Alentejana e Mertolenga têm condições para incorporar marcadores genéticos para a qualidade da carne e da carcaça nos seus programas de seleção
ABSTRACT - The selection of the carcass characteristics and meat quality, which are normally evaluated postmortem is complicated, hence the use of molecular markers can provide an alternative strategy in animal breeding. This work was performed using a total sampling of 273 animals from 9 cattle breeds/populations from Brazil (Angus, Holstein, Simental, Pardo Suíço x Holstein crossbreed, Montana, Guzerá x Holstein crossbreed, Gir, Nelore and Tabapuã) and 211 animals from Blanc Bleu Belge (BBB) and to Portuguese - Alentejana and Mertolenga - breeds, in order to assess its genetic characterization in 20 SNP (CAPN316; CAPN530; CAPN4751; CAPN4753; CAPN5331; CAST257; CAST2959; LEP140; LEP252; LEP305; UASMS1; UASMS2; UASMS3; nt414; nt419; Q204X; E226X; nt821; E291X; C313Y) located within the calpain, calpastatin, leptin and myostatin genes. The genotypic and allelic frequencies of SNP's located within the genes coding for calpain (μ-calpain) and calpastatin showed very similar distributions to those found by other authors. In the leptin gene, the differences observed between the animals from Brazil and Portugal, suggested that these groups of animals have distinct genetic influences (Bos indicus and Bos taurus), and possibly may have been subject to different selection processes. In the breed Mertolenga the ++ genotype in SNP nt821 within GDF8 gene is associated with better genetic maternal ability, growth capacity and productive longevity values, but with worse breeding values for calving interval. The results have shown that freezing caused an effect on the physical characteristics of the meat (color, shear force, water holding capacity and pH), but with some differences among breeds. The meat tenderness is influenced by genotypes of markers CAPN316, CAPN4751, CAST2 and LEP140, with maximum differences of the FC value of 2.35 Kgf, 4.96 Kgf, 5.24 kgF and 9,04 Kgf, respectively. The UASMS3 marker influences the percentage of trans AGM of the meat of Alentejana breed, while CAPN530 and LEP252 markers influence the percentage of SFA C16: 0 and n3 LCFA of the Mertolenga meet. The results confirm the usefulness of genetic markers for genetic improvement, and show that breeds Alentejana and Mertolenga may be amenable to incorporate genetic conditions for meat and carcass quality in their programs of selection markers.

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Keren, Boris. "La déficience intellectuelle : du diagnostic en puces ADN à l'identification de gènes candidats." Phd thesis, Université René Descartes - Paris V, 2013. http://tel.archives-ouvertes.fr/tel-00918306.

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L'analyse chromosomique sur puce ADN (ACPA) tend à devenir le principal examen diagnostique dans la déficience intellectuelle (DI). Parmi les techniques d'ACPA, les puces SNP ont l'intérêt de pouvoir détecter les pertes d'hétérozygotie, et par conséquent d'identifier les isodisomies uniparentales (iUPD) et les zones d'identité liées à la consanguinité. Nous avons étudié une cohorte de 1 187 patients atteints de DI, dans un cadre diagnostique, sur puces SNP. Nous avons réalisé, par cette étude, 145 diagnostics (12%) dont 2 iUPD et 6 délétions n'incluant qu'un seul gène. De plus, nous avons détecté 639 CNV rares non décrits chez des sujets contrôles et incluant des séquences codantes, ce qui nous a permis d'identifier 11 gènes candidats dans la DI : CAMTA1, SP3, CNTNAP4, NUDT12, STXBP6, DOCK8, DOCK10, SMARCA2, NYAP2, ATAD3A et ATAD3B. Nous avons tenté de valider l'implication de ces gènes par séquençage, mais n'avons trouvé de seconde mutation pour aucun d'entre eux. Toutefois, des réarrangements de CAMTA1 ont été retrouvés dans 2 autres familles avec un phénotype homogène (DI et ataxie congénitale) ce qui nous a permis d'affirmer qu'il s'agit d'un gène de DI. Par ailleurs, l'homozygosity mapping, réalisé avec puces SNP, a identifié, par séquençage whole exome, une mutation non-sens homozygote du gène BUD13 dans une famille de DI syndromique. Enfin, de façon fortuite, nous avons caractérisé en ACPA une translocation familiale entraînant une disruption d'un gène d'ataxie spino-cérébelleuse, ATXN10, ce qui a permis de mieux comprendre la physiopathologie de cette maladie. Au total, notre étude démontre l'intérêt des puces SNP dans la DI, d'une part en diagnostic et d'autre part pour l'identification de nouveaux gènes responsables de DI.

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Lin, Kuan-chin. "Candidate Gene Expression and SNP Analyses of Toxin-Induced Dilated Cardiomyopathy in the Turkey(Meleagris gallopavo)." Thesis, Virginia Tech, 2006. http://hdl.handle.net/10919/42012.

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Dilated cardiomyopathy (DCM), a heart disease, affects many vertebrates including humans and poultry. The disease can be either idiopathic (IDCM) or toxin-induced. Idiopathic DCM often occurs without a consensus cause. Though genetic and other studies of IDCM are extensive, the specific etiology of toxin-induced is still unknown. Here, our objective was to compare the level of mRNA expression of two candidate genes including troponin T (cTnT) and phospholamban (PLN) using quantitative reverse transcription polymerase chain reaction (RT-PCR) in toxin-induced DCM affected and unaffected turkeys. Cardiac TnT and PLN were chosen because their spontaneous expression has been reported to be associated with IDCM. We also scanned these genes for single nucleotide polymorphisms (SNPs) that could be useful in evaluating their functions in the incidence and severity of toxin-induced DCM in turkeys. There were no significant differences between affected and unaffected birds in the expression of both cTnT and PLN. A total of 12 SNPs were detected in cTnT and PLN DNA sequences. One of the seven haplotypes detected in cTnT was the most frequent. Linkage analysis showed that cTnT gene was unlinked on the current turkey genetic map. Resources developed here, including SNPs, haplotypes, cDNA sequences, and the PCR-RFLP genotype procedure will be used for future investigations involving cTnT and PLN and toxin-induced DCM.
Master of Science

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Ribeca, Cinzia. "Association between multiple candidate genes and carcass and beef quality in Pemontese cattle." Doctoral thesis, Università degli studi di Padova, 2011. http://hdl.handle.net/11577/3422007.

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The consumer is becoming more conscious about the quality of products and he is willing to pay more for superior products. To respond to the new and diversified consumer demand it is necessary to develop animal production with concerns of safe and quality products. Meat quality is a complex concept including carcass composition and conformation, lack of microbiological hazards, animal welfare and environmental impact. Traits concerning beef quality have low/medium heritabilities, and measures are difficult and expensive to be carried out. The development of DNA technologies applied to cattle represents a promising tool suitable to solving these problems. Markers found in various candidate genes linked to quality traits have been identified and included into a commercially genetic test for carcass/beef quality traits. However, before including these candidate genes in genetic tests and using them in breeding programs it is important to perform validation studies in different breeds to establish whether the observed marker effects are found in the breed or population of interest. Aims of this thesis were to analyze a group of candidate genes polymorphisms in order to provide further information about their allelic frequencies in Piemontese population and their association with the main carcass/beef quality traits. A prescreening was carried out to investigate the variability of a set of polymorphisms located in 15 candidate genes for meat quality traits. Meat samples of Longissimus thoracis muscle collected on 1,208 Piemontese young bulls, progeny of 109 AI sire, were available. Phenotypic data for carcass and meat quality traits used included carcass weight (CW), shear force (SF), cooking loss (CL) and pH (pH24h). For each trait, 48 samples were chosen from each tail of the trait distribution. One or more single nucleotide polymorphisms (SNPs) were determined in the following candidate genes: calpastatin (CAST), calpain 1 (CAPN1), B and D cathepsin (CTSB, CTSD), growth hormone (GH), growth hormone receptor (GHR), pro-opiomelanocortin (POMC), pituitary-specific positive transcription factor 1 (POU1F1), melanocortin-4 receptor (MC4R), corticotrophin-realising hormone (CRH), insulin-like growth factor binding protein-3 (IGFBP3), diacylglycerol acyltransferase 1 (DGAT1), thyroglobulin (TG), carboxypeptidase E (CPE), and protein kinase adenosine monophosphate-activated γβ-subunit (PRKAG3). A total of 20 SNPs were genotyped using allele refractory mutation system polymerase chain reaction (ARMS-PCR) or restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR). Allelic frequencies, test for Hardy-Weinberg (HW) equilibrium, as well as genic differentiation for sampled populations (i.e., 2 sub-populations per trait corresponding to the tails of its phenotypic distribution) were obtained using Genepop software version 4.0. A total of 6 SNPs showed a minor allele frequency less than 10%. Samples from the tails of each trait distributions were treated as different populations to investigate any possible difference in allelic frequencies. Only MC4R locus showed a significant difference in the allelic frequency across tails for CW. Based on these results, only variable loci were further investigated (Chapter 3). It was demonstrated that calpain system (μ-calpain, m-calpain, and calpastatin) and a lysosomal enzyme (cathepsin) influence some meat quality traits. In this study, 5 SNPs previously tested: CAPN530 (AF_288054.2:g.4558G>A), CAPN4751 (AF_288054.2:g.6545C>T), CAST2959 (AF_159246.1:g.2959A>G), CAST2870(AF_159246.1:g.2870A>G), CAST282 (AY_008267:g.282G>C) and CTSD (AB_055312:g.77G>A), were investigated in 990 Piemontese young bulls. A univariate Bayesian mixed-inheritance animal model was used to evaluate the effects of genotypes on variation of pH24, lightness (L*), redness (a*), yellowness (b*), cooking loss (CL), drip loss (DL), and shear force (SF). An association was observed only for CAST282 G allele and CAPN530 A allele on DL, CAPN530 A allele was also associated with b* and CAST2959 A allele with a*. It is reasonable to hypothesize that the effect obtained in this study might has been due to a variation of degradation of myofibril proteins and consequently activation/deactivation of drip channel that origin drip losses (Chapter 4). The last 10 variable polymorphisms tested in the prescreening phase were: GH1547 (M57764:g.1547TC>G), GHR257 (AF_140284:g.257A>G), POMC254 (J00021:g.254C>T), POU1F1 208 (EF090615:g.208A>G), MC4R1069 (AF_265221:g.1069C>G), CRH240 (AF_340152:g.240G>C), DGAT10343 (AJ_318490:g.10343GC>AA), TG1696 (M35823:g.1696C>T), CPE601 (AY_970663:g.601C>T), and PRKAG3 1609 (AY_692035:g.1609G>A). All of these SNPs were analyzed to calculate allelic frequency and to test their association with CW, pH24h, L*, a*, b*, CL, DL, and SF. All SNPs were informative in Piemontese population except for CPE601. Bayesian association analysis showed that 8 out of the 10 investigated SNPs had and additive deviation with at least one of the carcass and beef quality traits investigated. Some of these associations were new, whilst others confirmed previous investigations (Chapter 5).
Il consumatore sta diventando sempre più consapevole della qualità dei prodotti alimentari ed è disposto a pagare di più prodotti di qualità superiore. Per far fronte alle nuove e diversificate richieste dei consumatori, è necessario migliorare la produzione animale prestando particolare attenzione alla sicurezza e alla qualità. La qualità della carne è un concetto complesso che include composizione e conformazione della carcassa, assenza di rischi microbiologici, benessere animale e impatto ambientale. I caratteri che influenzano la qualità delle carni bovine hanno ereditabilità medio/bassa e inoltre misurarli è spesso difficile e costoso. Lo sviluppo delle tecnologie basate sul DNA, applicate agli animali da reddito, rappresenta un promettente strumento adatto a risolvere tali problemi. Molti marcatori presenti su geni candidati per la qualità della carne sono stati identificati e inclusi in test disponibili in commercio. Tuttavia prima di utilizzare questi test in programmi di miglioramento genetico è importante valutare se e quali effetti questi geni hanno nella popolazione in cui si vogliono utilizzare. Gli obiettivi di questa tesi sono stati: analizzare un gruppo di polimorfismi di geni candidati, al fine di fornire informazioni sulle loro frequenze alleliche nella popolazione Piemontese e valutarne l’associazione con i caratteri per la qualità della carcassa e della carne. Una pre-analisi è stata eseguita per individuare la variabilità di venti polimorfismi a singolo nucleotide (SNP) situati su quindici geni candidati per la qualità della carne. I campioni di Longissimus thoracis sono stati prelevati da 1.208 vitelloni Piemontesi, generati da 109 tori del centro d’inseminazione artificiale. Su tali campioni erano disponibili i dati fenotipici per la conformazione della carcassa e per la qualità della carne: peso della carcassa (CW), forza di taglio (SF) perdite di cottura (CL), e pH (pH24). Per ogni carattere, quarantotto campioni sono stati scelti da ciascuna delle due code della distribuzione normale del carattere stesso. Uno o più polimorfismi a singolo nucleotide (SNP) sono stati determinati nei seguenti geni candidati: calpastatina (CAST), calpaina 1 (CAPN1), B e D catepsina (CTSB, CTSD), ormone della crescita (GH), recettore dell’ormone della crescita (GHR), pro-opiomelanocortina (POMC), POU classe 1 homeobox 1 (POU1F1), recettore della melanocortina-4 (MC4R), ormone corticotropina rilasciante (CRH), proteina legante il fattore di crescita insulino-simile 3 (IGFBP3), diacilglicerolo aciltransferasi 1 (DGAT1), tireoglobulina (TG), carbossipeptidasi E (CPE) e subunità -γβdella proteina chinasi AMP-attivata (PRKAG3). Venti SNPs sono stati sottoposti a genotipizzazione mediante tecniche basate sulla reazione a catena sella polimerasi (PCR). Le frequenze alleliche, il test di equilibrio di Hardy-Weinberg (HW), così come la differenziazione genica per le popolazioni campionate (ovvero, due sub-popolazioni una per ciascuna coda della distribuzione del carattere) sono stati ottenuti utilizzando il software Genepop la versione 4.0. Un totale di sei SNPs ha presentato alleli minori con frequenza inferiore al 10%. I campioni presi delle code delle distribuzioni di ogni carattere sono stati trattati come popolazioni diverse al fine di rilevare eventuali differenze tra le frequenze alleliche. Solo il locus MC4R ha mostrato una differenza statisticamente significativa nella distribuzione allelica tra le due popolazione per il CW. I loci variabili ottenuti da questa prima analisi saranno analizzati su tutto il campione (capitolo 3). E’ stato dimostrato che sia il sistema calpaina/calpastatina (μ-calpaina, m-calpaina e calpastatina) sia un enzima lisosomiale (catepsina) influenzano alcuni caratteri legati alla qualità della carne. In questo studio cinque SNP, testati in precedenza: CAPN530 (AF_288054.2: g.4558G> A), CAPN4751 (AF_288054.2: g.6545C T>), CAST2959 (AF_159246.1: g.2959A> G), CAST2870 (AF_159246.1: g.2870A> G), CAST282 (AY_008267: g.282G> C) e CTSD (AB_055312: g.77G> A) sono stati genotipizzati su 990 vitelloni Piemontesi. Un animal model implementato con metodi Bayesiani è stato utilizzato per valutare gli effetti dei genotipi sulle variazione di pH24, di luminosità (L *), del rosso (a *), del giallo (b *), delle perdite di cottura (CL), delle perdite di gocciolamento (DL) e della forza di taglio (SF). L'associazione con la DL è stata osservata solo per CAST282 allele G e CAPN530 allele A. L’allele A di CAPN530 ha presentato associazione anche con a * e b * e l’allele A di CAST2959 con a*. Si potrebbe ipotizzare che l'effetto ottenuto, in questo studio, sul DL sia dovuto ad una variazione nella degradazione delle proteine miofibrillari che determina l'attivazione/disattivazione dei canali causando così la perdita d’acqua (capitolo 4). Gli ultimi dieci polimorfismi, risultati variabili nelle pre-analisi, sono: GH1547 (M57764: g.1547TC> G), GHR257 (AF_140284: g.257A> G), POMC254 (J00021: g.254C T>), POU1F1 208 (EF090615: g 0,208 A> G), MC4R1069 (AF_265221: g.1069C> G), CRH240 (AF_340152: g.240G> C), DGAT10343 (AJ_318490: g.10343GC> AA), TG1696 (M35823: g.1696C T>), CPE601 (AY_970663: g.601C T>), e PRKAG3 1609 (AY_692035: g.1609G> A). Tutti questi SNP sono stati genotipizzati per calcolarne le frequenze alleliche e per testare la loro associazione con CW, PH24h, L *, a *, b *, CL, DL, e SF. Tutti gli SNPs sono risultati informativi nella popolazione Piemontese, tranne CPE601. L’Analisi statistica ha dimostrato che otto dei dieci SNPs indagati avevano effetto additivo con almeno un carattere relativo alla qualità della carcassa e delle carni bovine. Alcune di queste associazioni sono presentate per la prima volta, mentre altre hanno confermato studi già effettuati (capitolo 5).

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CASELLA, LAURA. "SNP ANALYSIS FOR DROUGHT-RELATED CANDIDATE GENES IN A GERMPLASM COLLECTION AND A TILLING POPULATION OF ITALIAN RICE." Doctoral thesis, Università degli Studi di Milano, 2012. http://hdl.handle.net/2434/203361.

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Rice is the most important food crop in the world, representing the main source of caloric intake for more than one third of the world’s population. Although a great part of the global rice production comes from the developing countries such as China, India, Indonesia and Bangladesh, northern Italy plays a relevant role in terms of rice production providing about 50% of the total European paddy rice production. Due to the nature of the area devoted to rice growth, characterized by large availability of water and an efficient water distribution net, rice in Italy developed in the last two centuries as a water demanding crop, completing its growth cycle under submersion. However in the last decades also these regions experienced a reduction in water availability, with consequences on production and quality. The development of new varieties able to cope with water scarcity is therefore becoming of utmost importance for a sustainable rice cultivation in Italy. This study aims at identifying new alleles with added value for the improvement of drought resistance in Italian rice. The EMS-induced genetic variability in drought-related candidate genes was then explored in a TILLING population developed in the Italian rice variety Volano. The Volano TILLING platform was validated through the screening of three relevant target genes. A mutation density of 1/374 kb was estimated, proving the effectiveness of this approach for targeted rice crop improvement of Italian germplasm. The collection, currently consisting of 1860 mutant lines that are being enlarged with new mutagenized lines, represents an interesting source of variation exploitable in terms of response to drought stress and directly of use for targeted breeding programs. The mutant lines identified, affecting genes shown to be involved in plant drought escape and avoidance strategies, not only are relevant for Volano breeding programs, but represent a powerful genetic material in view of breeding for drought improvement in Italian rice. The second part of the work aimed at understanding the genetic determinants of root system architecture in the Italian rice germplasm, considering the profound implications of root development on the ability of the plant to cope with water deficits. The first Genome-Wide Association study on root traits was then performed on a germplasm collection including local accessions representing the genetic diversity of rice cultivated in Italy and a set of foreign varieties from temperate areas adapted to Italian climatic conditions. Whole genome genotyping was performed at Cornell University using the GBS (Genotyping-by-Sequencing) approach, a novel NGS strategy previously applied with success to maize and barley that uses libraries based on reducing genome complexity by methylation-sensitive restriction enzymes. In parallel, a thorough phenotypic screening for root morphological features was performed under controlled greenhouse conditions using a novel root phenotyping method that combines an optimized plant growing system (plastic cylindrical baskets coupled with PVC pipes) with an efficient imaging analysis (WinRHIZO image analysis software). The results of genome-wide association analyses performed on a first set of root phenotypic traits were very encouraging. All the detected significant associations were co-localizing with root QTLs previously identified in bi-parental mapping populations. Moreover, four of the detected regions co-localized with drought-avoidance QTLs, strongly supporting the hypothesis of their possible involvement in plant ability to cope with water scarcity. This work provides an initial study paving the way towards improvement of Italian rice varieties in terms of drought resistance.

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13

Arnold, Brenda Elaine. "Identification Of Candidate Genes For Self-Compatibility In A Diploid Population Of Potato Derived From Parents Used In Genome Sequencing." Thesis, Virginia Tech, 2013. http://hdl.handle.net/10919/51653.

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Gametophytic self-incompatibility limits the ability to derive inbred lines of potato through self-pollination and is prevalent in diploid potato. Within a population of F1 hybrids between two genotypes used in potato genome sequencing, we observed fruit set on many greenhouse-grown plants. Subsequently, after controlled self-pollinations, we confirmed fruit set in 32 of 103 F1 plants. Our goal was to identify genes responsible for self-compatibility in this population and to advance selfed progeny to develop highly homozygous inbred lines. The F1 population was genotyped using a single nucleotide polymorphism (SNP) array. Polymorphic and robust SNPs were analyzed by Fisher\'s Exact Test to identify allelic states segregating with the self-compatible phenotype. Filtering 1966 SNPs to retain only those with p-values less than 0.0001 yielded 95 highly significant SNPs, with all SNPs on anchored scaffolds located on chromosome 12. Candidate genes encoding for multiple notable proteins including an S-protein homologue were identified near highly significant SNPs on the Potato Genome Browser. Seeds obtained after self-pollination of self-compatible individuals were used to advance the population for three generations. SNP chip genotyping of the S3 generation revealed entirely different SNPs segregating for self-compatibility on nine different chromosomes. Comparison of the allelic state of SNPs in the F1 and S3 generations revealed a heterozygosity reduction by 80%, with fixation of many SNPs including those surrounding the S-protein homologue. We conclude that the genes responsible for segregation of self-compatibility in the S3 generation are different from those in the F1 generation.
Master of Science

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14

Ferreira, Leonardo Capistrano. "Genes candidatos de suscetibilidade a pr?-eclampsia: estudo de associa??o." Universidade Federal do Rio Grande do Norte, 2010. http://repositorio.ufrn.br:8080/jspui/handle/123456789/12565.

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Made available in DSpace on 2014-12-17T14:03:34Z (GMT). No. of bitstreams: 1 LeonardoCF_DISSERT_1_30.pdf: 1416070 bytes, checksum: 28ab6b39aaaf4f25a511c52c766f780f (MD5) Previous issue date: 2010-08-02
Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico
Preeclampsia is a multifactorial disease of unknown etiology that features with wide clinical symptoms, ranging from mild preeclampsia to severe forms, as eclampsia and HELLP syndrome. As a complex disease, preeclampsia is also influenced by genetic and environmental factors. Aiming to identify preeclampsia susceptibility genes, we genotyped a total of 22 genetic markers (single nucleotides polymorphisms SNPs) distributed in six candidates genes (ACVR2A, FLT1, ERAP1, ERAP2, LNPEP e CRHBP). By a case-control approach, the genotypic frequencies were compared between normotensive (control group) and preeclamptic women. The case s group was classified according to the disease clinical form in: preeclampsia, eclampsia and HELLP syndrome. As results we found the following genetic association: 1) ACVR2A and preeclampsia; 2) FLT1 and severe preeclampsia; 3) ERAP1 and eclampsia; 4) FLT1 and HELLP syndrome. When stratifying preeclampsia group according to symptoms severity (mild and severe preeclampsia) or according to the time of onset (early and late preeclampsia), it was detected that early preeclampsia is strongly associated to risk preeclampsia, eclampsia and HELLP syndrome have different genetic bases, although FLT1 gene seems to be involved in preeclampsia and HELLP syndrome pathophisiology
A pr?-ecl?mpsia ? uma doen?a multifatorial de etiologia ainda desconhecida que apresenta um amplo espectro quanto ? gravidade dos sintomas, podendo variar da forma mais branda (pr?-ecl?mpsia leve) ?s formas mais severas (ecl?mpsia e s?ndrome HELLP). Atualmente sabe-se que a pr?-ecl?mpsia ? influenciada tanto por fatores ambientais quanto por fatores gen?ticos. Com o prop?sito de identificar genes de suscetibilidade ? doen?a, genotipamos um total de 22 marcadores gen?ticos distribu?dos em seis genes candidatos (ACVR2A, FLT1, ERAP1, ERAP2, LNPEP e CRHBP). Utilizando uma abordagem do tipo casocontrole, comparamos as freq??ncias genot?picas entre mulheres normotensas (controles) e mulheres com pr?-ecl?mpsia (casos). O grupo dos casos foi dividido de acordo a forma cl?nica da doen?a em: pr?-ecl?mpsia, ecl?mpsia e s?ndrome HELLP. Como resultado p?de-se constatar as seguintes associa??es gen?ticas: 1) ACVR2A e pr?-ecl?mpsia; 2) FLT1 e pr?-ecl?mpsia grave; 3) ERAP1 e ecl?mpsia; 4) FLT1 e s?ndrome HELLP. Ao estratificar o grupo da pr?-ecl?mpsia de acordo com a gravidade dos sintomas (pr?-ecl?mpsia leve ou grave) ou de acordo com o tempo de in?cio dos sintomas (pr?-ecl?mpsia precoce ou tardia), comprovamos que o grupo pr?-ecl?mpsia precoce est? fortemente associado aos gen?tipos de risco. Nosso trabalho sugere que a pr?-ecl?mpsia, ecl?mpsia e s?ndrome HELLP possuem bases gen?ticas distintas, embora o gene FLT1 pare?a estar envolvido na fisiopatologia da pr?-ecl?mpsia e s?ndrome HELLP

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15

Illa, Berenguer Eudald. "Mapatge de gens candidats implicats en la qualitat del fruit al presseguer." Doctoral thesis, Universitat de Barcelona, 2010. http://hdl.handle.net/10803/966.

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En els darrers anys, la important reconversió varietal ha permès una millor qualitat, més adaptada tan a les exigències de la producció com de la distribució i del consumidor. La primera generació de milloradors van posar tot el seu èmfasi en millorar les característiques comercials de la fruita com el color, la fermesa i el sabor. Tanmateix el mercat actual exigeix altres atributs de tipus organolèptic i nutricional, addicionals als anteriors. Entendre la base genètica que controla cadascun dels caràcters determinarà la nostra capacitat per obtenir uns fruits més atractius i sans per al consumidor.
A la població 'Texas' × 'Earlygold' (T×E) s'han mapat 206 gens candidats (GCs) relacionats amb l'expressió dels caràcters de qualitat de la fruita (creixement i maduració del fruit, textura, color, contingut de sucres i àcids orgànics i aroma) i 18 gens al·lergògens de presseguer i/o ametller responsables de l'aparició de reaccions al·lèrgiques. La comparació entre la posició dels GCs mapats i la dels QTLs detectats ha permès trobar algunes co-localitzacions.
Addicionalment, l'anàlisi comparativa entre la seqüència dels marcadors mapats a Prunus amb el mapa de la maduixa diploide i la seqüència completa de la pomera mostra elements comuns. La presència de blocs sintènics facilitarà la transferència del coneixement genètic entre les tres espècies i, a la vegada, permetrà proposar un hipotètic genoma ancestral per la família Rosaceae.
RESUMEN
En los últimos años, la importante reconversión varietal ha permitido una mejor calidad, más adaptada tanto a las exigencias de la producción como de la distribución y del consumidor. La primera generación de mejoradores puso todo su énfasis en mejorar las características comerciales de la fruta como el color, la firmeza y el sabor. Sin embargo el mercado actual exige otros atributos de tipo organoléptico y nutricional, adicionales a los anteriores. Entender la base genética que controla cada uno de los caracteres determinará nuestra capacidad para obtener unos frutos más atractivos y sanos para el consumidor.
En la población 'Texas' × 'Earlygold' (T×E) se han mapeado 206 genes candidatos (GCs) relacionados con la expresión de los caracteres de calidad de la fruta (crecimiento y maduración del fruto, textura, color, contenido de azúcares y ácidos orgánicos y aroma) y 18 genes alérgenos de melocotonero y/o almendro responsables de la aparición de reacciones alérgicas. La comparación entre la posición de los GCs mapeados y la de los QTLs detectados ha permitido encontrar algunas co-localizaciones.
Adicionalmente, el análisis comparativo entre la secuencia de los marcadores mapeados a Prunus con el mapa de la fresa diploide y la secuencia completa del manzano muestra elementos comunes. La presencia de bloques sinténicos facilitará la transferencia del conocimiento genético entre las tres especies y, a la vez, permitirá proponer un hipotético genoma ancestral para la familia Rosaceae.
Fruit quality is a very important trait in breeding programs of rosaceous crops. In addition to attributes such as appearance, flavour, scent and texture, breeders focus more and more on crucial aspects like nutritional quality and the absence or significant reductions of allergenic compounds for fruit health and safety. Understanding the genetic basis that controls each character determines our ability to obtain more attractive and healthy fruit to consumers.
In the present study 206 candidate genes (CGs) associated with the expression of the characteristics of fruit quality (growth and fruit ripening, texture, colour, sugar content and organic acids and aroma) and 18 genes peach and / or almond allergens responsible for allergic reactions have been mapped in the Prunus reference map. The comparison between the position of the CGs and the QTLs previously detected allow us to find some co-localizations.
Additionally, the comparative analysis between the sequences of molecular markers that are anchored into the Prunus and Fragaria reference maps and the Malus genome sequence shows common features. The presence of syntenic blocks facilitates the transference of genetic information between the three species and, in turn, would propose a hypothetical ancestral genome for Rosaceae family.

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16

Manrique, Carpintero Norma Constanza. "Genetic studies of candidate genes in the glycoalkaloid biosynthetic pathway of potato." Diss., Virginia Tech, 2013. http://hdl.handle.net/10919/49619.

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Potato (Solanum tuberosum L) is an outcrossing, highly heterozygous cultivated in which the elucidation of the genetic basis of quantitative traits, is more complex than in self-pollinated crops. Both a candidate gene approach and a whole genome SNP genotyping analysis were used to assess allelic variation and to identify loci associated with biosynthesis and accumulation of steroidal glycoalkaloids (SGAs). SGAs are secondary metabolites produced in Solanum species as defense against insects and pathogens. Fragments of genomic DNA coding for regions of five SGA biosynthetic candidate genes were amplified, cloned and sequenced [3-hydroxy-3-methylglutaryl coenzyme A reductase 1 and 2 (HMG1, HMG2); 2,3-squalene epoxidase (SQE); solanidine galactosyltransferase (SGT1); and solanidine glucosyltransferase (SGT2)]. A germplasm panel of six wild potato species [Solanum chacoense (chc 80-1), S. commersonii subsp. commersonii, S. demissum, S. sparsipilum, S. spegazzinii, and S. stoloniferum] and a cultivated clone S. tuberosum Group Phureja (phu DH) was used in an allelic variation analysis. A segregating interspecific F2 population phu DH ï¿½" chc 80-1 was screened to assess association with SGAs. Sequence diversity analysis showed a tendency of purifying selection and increased frequency of rare alleles in most of the candidate genes. Genes of primary metabolism (HMG1, HMG2 and SQE) had stronger selection constraints than those in secondary metabolism (SGT1 and SGT2). Sequence polymorphism in HMG2, SQE, SGT1 and SGT2 separated either the phu DH clone which produced no SGAs, or chc 80-1, the greatest SGA accumulator, from other accessions in the panel. Segregation analysis of the F2 population revealed that allelic sequences of HMG2 and SGT2 derived from chc 80-1 were significantly associated with the greatest SGA accumulation. In the whole genome analysis, SNP genotyping and cluster analysis based on putative association with SGA accumulation in the germplasm panel, allowed identification of eight informative SNPs that can be used in future studies. In the segregating F2 population, loci located on five pseudochromosomes were associated with SGA synthesis. Loci on pseudochromosomes 1 and 6 explained segregation ratios of synthesis for Î±-solanine and Î±-chaconine, the most common SGAs in most potato species. In addition, loci on seven pseudochromosomes were associated with accumulation. New candidate genes, putatively affecting synthesis and accumulation of SGAs, were identified in adjacent genomic regions of significant SNPs. This research demonstrates how the newly available genome sequence of potato and associated biotechnological tools accelerates the identification of genetic factors underling complex traits in a species with a difficult breeding structure.
Ph. D.

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17

Tobouti, Priscila Lie. "Avaliação da expressão gênica da proteína aspartil secretada 2, 5 e 9 (SAP-2, SAP-5 e SAP-9) e sua correlação com a invasão epitelial por Candida albicans em modelo experimetal de estomatite protéica in vivo." Universidade de São Paulo, 2011. http://www.teses.usp.br/teses/disponiveis/25/25150/tde-27072011-110643/.

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A Estomatite protética associada a Candida (EPC) acomete a mucosa bucal em contato com próteses removíveis e, clinicamente, caracteriza-se por eritema com diferentes graus de inflamação. Esta doença é considerada de etiologia multifatorial, isto é, uma associação de fatores como trauma, falta de higienização, uso contínuo da prótese, hipersensibilidade ao material usado na dentadura, diabetes, terapia imunossupressora e infecção por fungo, como diferentes espécies de Candida. Os principais fatores de virulência deste fungo são a formação de hifas, dimorfismo, alterações fenotípicas, aderência, persistência, sinergismo com as bactérias, interferências com o sistema de defesa do hospedeiro e a produção de enzimas hidrolíticas. Dentre as enzimas hidrolíticas, a proteinase aspartil secretada (SAP) é uma das mais importantes para a patogenia de C. albicans, sendo nociva para o tecido epitelial e para o sistema imune do hospedeiro. Não está totalmente compreendida a real penetração do fungo nos tecidos e sua correlação com a presença da SAP, na doença estomatite protética. Essa dificuldade de avaliação pode ser justificada pelas divergências intrínsecas e extrínsecas observadas em muitos aspectos, como diferentes costumes, hábitos sociais, estado emocional e fisiológico. A utilização de um modelo experimental em animais poderá minimizar essas divergências e fornecer condições mais padronizadas para o experimento. Neste trabalho, foram avaliadas, quantitativamente, a expressão gênica das enzimas SAP-2, SAP-5 e SAP-9, presentes no biofilme formado na superfície interna das placas acrílicas superiores de ratos e, microscopicamente, a invasão do fungo no tecido epitelial do palato. Para isso, foram selecionados 49 ratos Wistar, com 90 dias de vida, pesando em média 300g, os quais foram divididos em 3 grupos: Controle, Placa/Candida e Placa, acompanhados durante 2, 4 e 6 dias. Os resultados demostraram que, em 4 dias de uso da placa acrílica contaminada, houve, em alguns ratos, sinais clínicos de inflamação no palato duro; microscopicamente, hiperplasia epitelial, hiperqueratinização, invasão fúngica nas camadas superficiais do revestimento epitelial, microabscessos de Munro e hiperplasia papilar; e maior percentual de neutrófilos no Grupo Placa/Candida em relação aos Grupos Controle e Placa. Também no quarto dia de uso da placa acrílica superior, no Grupo Placa/Candida, o biofilme formado na sua superfície interna apresentou a mais alta expressão gênica relativa das enzimas SAP-2, SAP-5 e SAP-9 que os períodos de 2 e 6 dias de uso. Assim, a invasão fúngica no revestimento epitelial do palato duro pode estar correlacionada com a alta expressão de RNAm das SAPs -2, -5 e -9.
Denture stomatitis (D.S.) affects the oral mucosa in contact with removable dentures, and clinically characterized by erythema with varying degrees of inflammation. This disease is considered a multifactorial etiology, with a combination of factors such as trauma, lack of hygiene, continuous use of stents, hypersensitivity to the material used for dentures, diabetes, immunosuppressive therapy and fungal infection, such as different species of Candida. The main virulence factors of the fungus are the formation of hyphae, dimorphism, phenotypic changes, adherence, persistence, synergism with bacteria, interference with the host defense system and the production of hydrolytic proteins. Among the hydrolytic proteins, the secreted aspartyl proteinase (SAP) is one of the most important in the pathogenesis of C. albicans. SAP is harmful to both the epithelial tissue and to the host\'s immune system. It is not fully understood the real penetration of the fungus in the epithelium tissue and its correlation with the presence of SAP, in denture stomatitis. This difficulty in evaluation can be justified by the intrinsic and extrinsic differences observed in many aspects, different customs, social`s habits, emotional and physiological state. Using an experimental animal model may minimize these differences and provide more standardized conditions for the experiment. In the present work, the aim was to evaluate quantitatively the gene expression of enzymes SAP-2, SAP-5 and SAP-9 of the biofilm formed in internal surface of rat`s upper acrylic plates, and to analysis microscopically, the fungal invasion in palatal epithelial tissue. 49 Wistar rats were selected, 90 days old, weighing on average 300g. They were divided into three groups: Control Group, Plate/Candida and Plate, follow by 2, 4 and 6 days of the use of the plates. The results demonstrated, in four days of use of the acrylic plate, clinical signs of inflammation in the hard palate; microscopically epithelial hyperplasia, hyperkeratinization, fungal invasion in the superficial layers of the epithelial lining, Munro`s microabscess and papillary hyperplasia; and higher percentage of neutrophils in the Plate/Candida Group, compared to Control and Plate Groups. In the period of 4 days, the relative gene expression of the SAPs-2, -5 and -9 in biofilm also showed to be higher in Plate/Candida Group, compared with the periods of 2 and 6 days. Thus, the fungal invasion in the epithelial lining of the hard palate may be correlated with high mRNA expressionn of SAPs -2, -5 e -9.

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18

Baison, John. "Mapping and identification of disease resistance candidate genes in three Malus populations using SSRs, DArT and Infinium SNP markers and Illumina sequencing technology." University of the Western Cape, 2014. http://hdl.handle.net/11394/4678.

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Philosophiae Doctor - PhD
Apple scab, powdery mildew and woolly apple aphid are a major concern for apple breeders and producers. Control of these diseases is a significant economic and marketing priority for the South African apple industry. Application of chemicals and orchard management practices are the main methods for controlling these diseases. These diseases require an average of 15 chemical sprays per season, which leads to increased production costs for the farmer. The increased cost of chemical based control programs and demand from consumers for ‘organic apples’ grown with very little to no chemical sprays makes it important to breed for commercial apple cultivars with endogenous disease resistance genes (R-genes). The use of genetic tools (apple genetic linkage maps and the apple genome sequence) to track and introgress endogenous R-genes in breeding and to confer durable disease resistance in commercial apple cultivars will lead to a more cost effective means of disease control for apple producers. Historically, most breeding programmes rely on recurrent conventional breeding systems. This involves the crossing of apple selections showing resistance to a given disease with a susceptible elite variety. This is followed by phenotyping the progeny to identify trees exhibiting segregating field resistance. Several crosses and backcrossing are required to produce resistant varieties and to fix the resistance trait using this breeding strategy. This breeding technique is time consuming, especially in perennial tree species such as apples, which have a long juvenile period. Molecular markers have enabled the building of genetic maps, which has allowed for tracking of the inheritance of genes contributing towards the observed resistances. This has given breeders the opportunity to start the implementation of marker-assisted-breeding (MAB) and marker-assistedselection (MAS). MAB and MAS greatly reduce the time required to select for favourable genotypes, given that MAB facilitates efficient selection for inherited traits at the seedling stage. With the publication of the apple genome sequence, the identification of the genes involved in disease resistances has been made possible and this will allow researchers to venture into cisgenics for apples, which will further reduce the time required for the introgression of desirable genes into commercial cultivars. The main thrust of this research was to generate dense genetic linkage maps for three mapping populations segregating for apple scab, woolly apple aphid and powdery mildew resistance. The three mapping populations are ‘Mildew Resistant’ x ‘Golden Delicious’, ‘Russian Seedling’ x ‘Golden Delicious’ and Malus platycarpa x ‘Mildew Resistant’ and are Malus full-sib outbreed mapping populations. The generation of the genetic maps was for use in the subsequent identification candidate disease resistance QTLs/genes that can be implemented in apple cisgenics. Integrated genetic maps using SSRs, DArTs and SNP marker data were generated for all the three crosses. The integrated map of ‘Mildew Resistance’ x ‘Golden Delicious’ consists of 1, 563 markers with a total map length of 1, 298.8 cM. The ‘Russian Seedling’ x ‘Golden Delicious’ genetic map is composed of 979 markers with a total map length of 1, 729.9 cM. The Malus platycarpa x ‘Mildew Resistant’ integrated map has 616 markers and a total map length of 1,324.3 cM. Due to the fragmentation of some of the linkage groups in the ‘Russian Seedling’ x ‘Golden Delicious’ and in the Malus platycarpa x ‘Mildew Resistant’ genetic maps, a phylogenetic analysis was performed to evaluate the genetic distances between the parents of the crosses in order to understand the cause of the fragmentation of these two integrated genetic maps. QTLs were detected through the statistical correlation of the phenotypic and map data using restricted Multiple QTL Mapping (rMQM) from MapQTL® 6.0. The genome-wide LOD score minimum QTL detection thresholds were determined using 10 000 permutations for each population. The minimum QTL detection threshold for accepting a putative QTL was then determined to be 4.5 for ‘Mildew Resistant’ x ‘Golden Delicious’ and 4.6 for both the ‘Malus platycarpa’ x ‘Mildew Resistant’ and ‘Russian Seedling’ x ‘Golden Delicious’ mapping populations. A total of 17 putative QTLs were detected for the ‘Mildew Resistant’ x ‘Golden Delicious’ population, 10 putative QTLs for the Malus platycarpa x ‘Mildew Resistant’ population and nine putative QTLs for the ‘Russian Seedling’ x ‘Golden Delicious’ population were detected for the three diseases under study. The two putative QTLs for apple scab resistance detected on LG 02 of the ‘Russian Seedling’ x ‘Golden Delicious’ map coincided with the loci previously identified as encoding two apple scab resistance genes Vh2 and Vh4 on ‘Russian apple’. The QTL for apple scab resistance identified on the proximal QTL of LG 02 co-localized with SNP marker R_8936738_Lg2 on the loci where Vh4 was previously identified. The distal QTL on LG 02 shown to encode the Vh2 R-gene was linked with the SNP marker R_32981524_Lg2. With ‘Russian apple’ being known to carry a natural pyramid of R-genes for apple scab on LG 02, therefore, the ‘Russian Seedling’ used in this study was screened by a set of 14 SSR markers to determine if it was related to ‘Russian apple. The 14 SSRs produced identical alleles to those amplified by ‘Russian apple’, which means “Russian Seedling’ and ‘Russian apple’ are closely related or identical. The LG 02 pseudo-chromosome sequence was extracted from the NCBI database housing the apple genome sequence and was then used to mine for the putative R-genes within the two QTL regions. The region corresponding to the Vh2 loci, which was roughly a 600 kb region, had two clusters of ABC (PDR) disease resistance related genes. These were predicted using a full Pfam domain search and were only detected on the negative strand. The 60 kb region corresponding to the Vh4 loci comprised a cluster of LRR domains that were also detected on the negative strand using a full Pfam domain search. This 60 kb region was further analysed using Phytozome and Genome Database for Rosaceae (GDR) leading to two candidate disease resistance genes being identified. Ten consensus gene sequences were present within the 60 kb region, with only two transcripts MDP0000657246 and MDP0000128458 identified as being disease resistance related genes. The MDP0000657246 was identified on the contig MDC000294 of the Malus x domestica reference genome as being a Leucine Rich Repeat protein kinase family, which is one of the most abundant disease resistance family mainly involved in the gene-for-gene resistance mechanism. The MDP0000128458 locus was identified on contig MDC015161 as being a Ser/Thr phosphatase 7. The Ser/Thr phosphatase genes have been associated with the regulation of MAP kinase cascades that have been shown to induce the hypersensitive response (HR) in tobacco. Therefore these two genes are likely to be the loci associated with the hypersensitive response associated with the infection of apples with race 4 of apple scab, carrying the Vh4 apple scab resistance gene. Recurrent putative QTLs were detected that still need to be validated in order to be used for MAB. The ‘Russian Seedling’ x ‘Golden Delicious’ cross produced a single powdery mildew resistance QTL located on LG08 and conferring a 1:1 resistance to susceptible phenotypic segregation ratio. These results indicate that the source of the resistance thus was a single dominant resistance gene. The ‘Mildew Resistant’ x ‘Golden Delicious’ mapping population also showed two stable QTLs one for powdery mildew on LG 03, which co-segregated with SNP GD_LG03snp00866 and in addition SNP R_13071892_Lg10 was also identified to be co-segregating with the QTL for apple scab resistance on LG10. However, none of these recurrent QTLs co-localized with known genes or QTLs. For the phylogenetic analysis, re-sequenced data using the Illumina® sequencing technologies and the apple SNP chip data for ‘Russian Seedling’, ‘Mildew Resistant’, Malus platycarpa, a Chinese accession of Malus sieversii and ‘Anna’ where used to infer relatedness of the five genotypes. The Chinese accession of Malus sieversii was included in the analysis since ‘Russian Seedling’ was thought to be relatively close genetically. Whilst ‘Anna’ is known to be a low chilling cultivar of Malus x domestica (Borkh) and therefore would add in the phylogenetic placement of ‘Mildew Resistant’ and Malus platycarpa. These were sequenced to coverage of approximately 60X for ‘Russian Seedling’ and 6X for the other four genotypes. The sequence data was aligned to the reference Malus x domestica cv Golden Delicious mitochondrial genome sequence. Phylogenetic analysis was then performed using both the data from the apple SNP-chip and the aligned mitochondrial genomes. The results from both sets of data supported the putative evolutionary distances between the five genotypes. ‘Russian Seedling’ and M. sieversii were closely related, while both were genetically divergent from the closely related ‘Anna’ and ‘Golden Delicious’ commercial cultivars. This analysis however indicated that ‘Mildew Resistant’ was relatively closely related to ‘Golden Delicious’ and hence the low number of markers showing segregation distortions for the ‘Mildew Resistant’ x ‘Golden Delicious’ population in the 17 LGs of the integrated map. However, the other two mapping population exhibited a high number of markers with segregation distortions. Markers which are closely associated with disease resistance to apple scab powdery mildew and woolly apple aphid resistance will play a major role in the identification of the genes responsible for the resistances being observed. The identification of the two candidate genes for the Vh4 gene associated with apple scab resistance will be the platform from which a cisgenic programme can be implemented in the South African apple breeding program.

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19

Avgan, Nesli. "The genetic basis of human cognition: Intelligence, learning and memory." Thesis, Queensland University of Technology, 2018. https://eprints.qut.edu.au/122903/1/Nesli_Avgan_Thesis.pdf.

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The complex and highly polygenic traits of intelligence, learning and memory are fundamental functions of neurocognition. Despite improvements in neurogenetics, our knowledge on the genetic architecture of these functions remains poorly understood. This research investigated the contribution of genetic variation to cognitive performance variability in relation to intelligence, learning and memory using a well-defined, healthy and unrelated cohort via a gene-centric and a genome-wide approach. Results of this study validated several previously identified genes, provided new knowledge on various cognitive traits, and identified several novel regions for future studies that may have consequences for managing disorders involving cognitive impairments.

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20

SILVA, Naiara Chaves. "Análise de aspartato protease (sap) como fator associado à virulência de linhagens de Candida albicans e Candida não-albicans." Universidade Federal de Alfenas, 2013. https://bdtd.unifal-mg.edu.br:8443/handle/tede/285.

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Candida spp. se tornaram, nas últimas décadas, importantes agentes causadores de infecções invasivas, responsáveis por altos índices de morbidade e mortalidade. Acredita-se que a aspartato protease secretada (Sap) seja um fator diretamente associado aos processos infecciosos exercendo papel determinante na patogenicidade de Candida spp. e que a exposição a concentrações subinibitórias de antifúngicos, pode aumentar a produção de Sap e selecionar isolados resistentes. Analisaram-se isolados de Candida albicans e Candida não-albicans oriundos de casos de infecção hospitalar. Avaliou-se o perfil proteico destes isolados por eletroforese SDS-PAGE. Avaliou-se, também, o perfil de sensibilidade dos isolados frente a antifúngicos de uso convencional em esquemas terapêuticos (fluconazol e anfotericina B) e a antifúngicos mais novos que ainda não fazem parte das rotinas hospitalares (voriconazol e caspofungina). Determinou-se a atividade proteolítica qualitativa e quantitativa de Sap e atividade metabólica de C. albicans e Candida não-albicans cultivados na presença e ausência de concentrações subinibitórias de fluconazol e anfotericina B. Estabeleceu-se a correlação entre os testes e por fim, avaliou-se a expressão do gene SAP2 em C. albicans ATCC 64548 e C. krusei ATCC 6258. 100% dos isolados foram sensíveis a anfotericina B, voriconazol e caspofungina e 89,9% a fluconazol. Dois isolados (7,4%) apresentaram sensibilidade dependente da dose e um (3,7%) apresentou resistência ao fluconazol. Na análise qualitativa da atividade proteolítica, 77,7% dos isolados apresentaram atividade. A maioria dos isolados de C. albicans (50%) e Candida não-albicans (32%) apresentou atividade proteolítica moderada. A adição de fluconazol ao cultivo não promoveu alterações significativas na atividade proteolítica dos isolados padrões, enquanto anfotericina B inibiu o crescimento de C. glabrata ATCC 90030 e C. krusei ATCC 6258. Na análise quantitativa, todos os isolados se apresentaram ativos, sendo que a maior atividade foi observada em Candida complexo “psilosis” 210 (100%) e a menor em C. albicans 257 (2,44%). A maioria dos isolados de C. albicans (50%) foi classificada como fracamente proteolítica, enquanto Candida não-albicans (53%) como moderadamente proteolítica. A presença de antifúngicos no cultivo alterou significativamente o percentual de degradação da maioria dos isolados. A maior diferença de percentual foi observada em C. lusitaniae 286, que na presença de ¼ da IC90 de anfotericina B aumentou 13,7x em relação à ausência do fármaco. O método quantitativo de determinação da atividade proteolítica apresentou maior sensibilidade. 63% dos isolados de C. albicans apresentaram alta atividade metabólica e 68% de Candida não-albicans, atividade moderada. A maior atividade metabólica foi observada em C. albicans 120 (61,72%) e a menor em C krusei ATCC 6258 (2,35%). A atividade metabólica da maioria dos isolados foi significativamente alterada. A maior diferença de percentual foi observada em Candida complexo “psilosis” 210, que na presença de ½ da IC50 de fluconazol apresentou redução de 8x na atividade metabólica em relação à ausência do fármaco. Houve expressão de SAP2 apenas em C. albicans ATCC 64548, que foi reduzida significativamente na presença de ¼ da IC90 de anfotericina B. A atividade de Sap pode ser considerada um fator potencial associado à virulência, uma vez que o isolado que apresentou a maior atividade apresentou sensibilidade antifúngica reduzida.
Candida spp. has become in recent decades, major causative agents of invasive infections, responsible for high rates of mortality and morbidity. It is believed that the secreted aspartate protease (Sap) is a factor directly associated with infection exerting decisive role in the pathogenicity of Candida spp. and that the exposure to subinibitory concentrations of antifungals may increase the production of Sap and to select resistant isolates. We analyzed isolates of Candida albicans and Candida non-albicans from cases of hospital infection. We evaluated the protein profile of the isolates of Candida spp. by SDS-PAGE. We evaluated also the susceptibility profile of the isolates against antifungals of use conventional in regimens therapeutics (fluconazole and amphotericin B) and newer antifungals that are not yet part of the hospital routine (voriconazole and caspofungin). It was determined the proteolytic activity qualitative and quantitative of Sap and metabolic activity of isolates of C. albicans and Candida non-albicans grown in the presence and absence of subinhibitory concentrations of fluconazole and amphotericin B. Was established the correlation between the tests and, finally, the expression of the SAP2 gene in C. albicans ATCC 64548 and C. krusei ATCC 6258 was evaluated. 100% of the isolates were susceptible to amphotericin B, voriconazole and caspofungin and 89.9% to fluconazole. Two isolates (7.4%) showed susceptibility dose dependent and one (3.7%) showed resistance to fluconazole. In the qualitative analysis of proteolytic activity, 77.7% of the isolates showed activity. The most isolates of C. albicans (50%) and Candida non-albicans (32%) had moderate proteolytic activity. The addition of fluconazole to culture did not promote significant changes in the proteolytic activity of the isolates patterns, while amphotericin B inhibited the growth of C. glabrata ATCC 90030 and C. krusei ATCC 6258. In quantitative analysis, all isolates were active, being that the highest activity was observed in Candida complex “psilosis” 210 (100%) and the lowest in C. albicans 257 (2.44%). The most of the C. albicans isolates (50%) were classified as weakly proteolytic, while Candida non-albicans (53%) as moderately proteolytic. The presence of antifungals in the culture significantly changed the percentage of substrate degradation of the most of isolates. The greatest difference of percentage was observed in C. lusitaniae 286, which in the presence of ¼ IC90 of amphotericin B increased 13.7x regarding to absence of the drug. The quantitative method of determining the proteolytic activity presented greater sensitivity. 63% of the isolates of Candida albicans showed high metabolic activity and 68% of Candida non-albicans had moderate activity. The higher metabolic activity was observed in C. albicans 120 (61.72%) and lowest in C krusei ATCC 6258 (2.35%). The metabolic activity of the most of the isolates was significantly altered. The major difference of percentages was observed in Candida complex “psilosis” 210, which in the presence of ½ IC50 of fluconazole showed reduction of 8x in the metabolic activity regarding to absence of the drug. There was expression of SAP2 only in C. albicans ATCC 64548, which was significantly reduced in the presence of ¼ IC90 of amphotericin B. The Sap activity may be considered a potential factor associated to virulence, once that the isolate that showed the greatest activity showed susceptibility reduced.
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES

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21

Gameeldien, Hajirah. "The identification of candidate genes using cDNA microarray and the analysis of two SNPs of the reelin gene in a South African austistic population." Thesis, University of the Western Cape, 2009. http://etd.uwc.ac.za/index.php?module=etd&action=viewtitle&id=gen8Srv25Nme4_3430_1297755889.

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Autism is a pervasive developmental disorder (PDD) that&rsquo
s incidence is approximately 1 in 158. It is four times more prevalent in males than females and is believed to be caused by both genetic and environmental factors. Research indicates that several genes are involved in autism and it is believed that these genes act together to produce autism. Many genes implicated in this disorder are involved with brain structure formation and brain functioning. Studies have identified the reelin (RELN) gene as necessary for proper formation of brain, which indicates that RELN abnormalities could contribute to the aetiology of several neurogenetic diseases such as schizophrenia, bipolar and autism. The aims of the study were (i) to genotype two SNPs (exonic rs3622691 and intronic rs736707) in the RELN gene using Taqman®
SNP Genotyping assays to detect association with autism in three distinct South African (SA) ethnic groups (Black, Caucasian and Mixed), and (ii) to detect candidate genes that are over and under-expressed in the samples taken from a SA Caucasian autistic group and compare those with samples taken from a healthy Caucasian group using cDNA microarray. The Taqman®
study indicated significant association for the intronic SNP, rs736707, with a p-value of 0.0009 in the total SA group. More so, the Mixed group displayed the highest significance amongst the ethnic groups, with a p-value of 0.00014. The microarray study yielded 21 genes with 95% significance in the Caucasian sample group. Most genes were hypothetical proteins and formed part of the FAM90A family. The LOC83459 showed the highest level of expression in the autistic samples, while the BTNL8 gene was shown to be highly suppressed in the control samples.

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22

STAGNATI, LORENZO. "GENOME WIDE ASSOCIATION STUDIES TO IDENTIFY GENES FOR RESISTANCE TO FUSARIUM EAR ROT IN MAIZE." Doctoral thesis, Università Cattolica del Sacro Cuore, 2017. http://hdl.handle.net/10280/19083.

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Fusarium verticillioides è l’agente responsabile della Fusariosi della Spiga del mais, contamina la granella con fumonisine, micotossine responsabili di diverse patologie umane e animali. Per la resistenza alla fusariosi e all’accumulo di fumonisine esiste variabilità tra genotipi diversi ma non sono ancora disponibili ibridi immuni. L’obiettivo di questo lavoro è stato quello di individuare marcatori associati alla resistenza a F. verticillioides. Mediante un bioassay è stato testato un association panel per la resistenza a F. verticillioides. Al fine di identificare i marcatori di resistenza sono stati applicati un approccio GWAS e uno per geni candidati. L’analisi GWAS è stata eseguita con 227K SNPs restituendo 206 marcatori significativi. Da un lavoro di RNASequencing sono stati individuati i geni coinvolti nella risposta a F. verticillioides mentre i geni R sono stati recuperati della letteratura scientifica. Genotipi resistenti (CO433 e CO441) e suscettibili (CO354 e CO389) sono stati scelti per individuare polimorfismi nei geni candidati da associare ai fenotipi rilevati mediante il bioassay. Quattro marcatori sono risultati significativi. Infine, la correlazione tra l’incidenza della fusariosi rilevata in campo e mediante bioassay è stata analizzata in una popolazione di 172 RIL derivanti da CO441 x CO354, tuttavia, non è stata individuata alcuna corrispondenza.
Fusarium verticillioides is the causal agent of Fusarium ear rot (FER) in maize and contaminates grains with fumonisin, a family of mycotoxins involved in several human and animal diseases. Quantitative genetic variation exists for resistance to FER and fumonisin contamination among genotypes, however, resistant maize hybrids are currently not available. The aim of this work was the identification of genetic markers associated to resistance against F. verticillioides. A bioassay was used to screen inbred lines of the maize association population for FER resistance, GWAS and candidate gene approaches were applied to identify markers. GWAS was performed using a 227K SNP matrix and resulting in 206 significant markers. Genes involved in F. verticillioides response in developing maize kernels were retrieved from a previous RNASequencing study while maize R genes were retrieved from scientific literature. Resistant (CO433 and CO441) and susceptible genotypes (CO389 and CO354) were selected to amplify and sequence candidate genes. Polymorphisms detected were used to find association with phenotypes scored using the bioassay. Four significant markers were found. Finally, the correlation between FER phenotypes scored in field experiments and bioassay phenotypes was investigated. A population of 172 RILs (CO441 x CO354), was tested. No correlation was found.

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23

STAGNATI, LORENZO. "GENOME WIDE ASSOCIATION STUDIES TO IDENTIFY GENES FOR RESISTANCE TO FUSARIUM EAR ROT IN MAIZE." Doctoral thesis, Università Cattolica del Sacro Cuore, 2017. http://hdl.handle.net/10280/19083.

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Fusarium verticillioides è l’agente responsabile della Fusariosi della Spiga del mais, contamina la granella con fumonisine, micotossine responsabili di diverse patologie umane e animali. Per la resistenza alla fusariosi e all’accumulo di fumonisine esiste variabilità tra genotipi diversi ma non sono ancora disponibili ibridi immuni. L’obiettivo di questo lavoro è stato quello di individuare marcatori associati alla resistenza a F. verticillioides. Mediante un bioassay è stato testato un association panel per la resistenza a F. verticillioides. Al fine di identificare i marcatori di resistenza sono stati applicati un approccio GWAS e uno per geni candidati. L’analisi GWAS è stata eseguita con 227K SNPs restituendo 206 marcatori significativi. Da un lavoro di RNASequencing sono stati individuati i geni coinvolti nella risposta a F. verticillioides mentre i geni R sono stati recuperati della letteratura scientifica. Genotipi resistenti (CO433 e CO441) e suscettibili (CO354 e CO389) sono stati scelti per individuare polimorfismi nei geni candidati da associare ai fenotipi rilevati mediante il bioassay. Quattro marcatori sono risultati significativi. Infine, la correlazione tra l’incidenza della fusariosi rilevata in campo e mediante bioassay è stata analizzata in una popolazione di 172 RIL derivanti da CO441 x CO354, tuttavia, non è stata individuata alcuna corrispondenza.
Fusarium verticillioides is the causal agent of Fusarium ear rot (FER) in maize and contaminates grains with fumonisin, a family of mycotoxins involved in several human and animal diseases. Quantitative genetic variation exists for resistance to FER and fumonisin contamination among genotypes, however, resistant maize hybrids are currently not available. The aim of this work was the identification of genetic markers associated to resistance against F. verticillioides. A bioassay was used to screen inbred lines of the maize association population for FER resistance, GWAS and candidate gene approaches were applied to identify markers. GWAS was performed using a 227K SNP matrix and resulting in 206 significant markers. Genes involved in F. verticillioides response in developing maize kernels were retrieved from a previous RNASequencing study while maize R genes were retrieved from scientific literature. Resistant (CO433 and CO441) and susceptible genotypes (CO389 and CO354) were selected to amplify and sequence candidate genes. Polymorphisms detected were used to find association with phenotypes scored using the bioassay. Four significant markers were found. Finally, the correlation between FER phenotypes scored in field experiments and bioassay phenotypes was investigated. A population of 172 RILs (CO441 x CO354), was tested. No correlation was found.

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24

Maiga, Bakary. "Human candidate polymorphisms and malaria susceptibility in sympatric ethnic groups, The Fulani and The Dogon of Mali." Doctoral thesis, Stockholms universitet, Institutionen för molekylär biovetenskap, Wenner-Grens institut, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-99613.

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In malaria endemic regions, resistance to malaria constitutes a critical selective pressureon genetic polymorphisms that regulate immune defense and inflammatory pathways.Differences in malaria susceptibility between sympatric ethnic groups have been described inMali. The Fulani are less susceptible to malaria compared to the neighboring group the Dogon,in spite of similar socio-economic and environmental conditions. Paper I is focused on IL-4-590 T/C polymorphism and correlation with levels of malariaspecific IgG, IgG (1-4) subclasses as well as malaria specific and total IgE level in the two ethnicgroups. Our data show that the Fulani individual carrying the IL-4-590 T allele found to havehigher parasite carriage rate and had higher levels of malaria-specific IgG4 and IgE compared tothe individual carrying the C allele. No such differences were seen within the Dogon.Paper II investigated 166 SNPs in the human host in individuals belonging to the Fulani and theDogon ethnic groups. These SNPs were correlated with total IgG against AMA-1, MSP-1, MSP-2 and CSP antigens as well as total IgE level. All antibody levels were higher in the Fulanicompared to the Dogon and strengthens previous finding that antibodies might play a role in theprotection seen in the Fulani. We identified higher frequencies of the protective blood group O.Several allelic differences between the two ethnic groups were found in CD36, IL-4, RTN3 andADCY9. Moreover several polymorphisms in SLC22A4, IRF1, IL5, LTA and TNF have beenfound to be correlated with anti-MSP antibody level; TLR6, IL3, TNF, and IL22 found to becorrelated with anti-MSP-2 antibody level in the Fulani. Such association was not seen in theDogon. In Paper III, the same individuals, as in paper II, were investigated with a focus on the FcγRIIapolymorphism and correlation with levels of anti-AMA-1, MSP-1, MSP-2, CSP specificantibodies as well as total IgE level. The genotype distribution and allele frequency weresignificantly different between the Fulani and the Dogon with the Fulani being HH, H allele- andthe Dogon RR, R allele carriers. A correlation between the HH genotype and the H allele andprotection against mild malaria was seen in the Fulani but not in the DogonTaken together our study has found significant genetic differences between the Fulani and theDogon Ethnic groups, which suggest that ethnicity should be taken into account in monitoring ofimmunological studies and vaccines trials in malaria endemic areas.

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25

Saus, Martínez Ester. "Study of genomic variability in the genetic susceptibility to psychiatric disorders: SNPs, CNVs and miRNAs." Doctoral thesis, Universitat Pompeu Fabra, 2010. http://hdl.handle.net/10803/7221.

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In this thesis we have studied genetic elements potentially contributing to the pathophysiology of psychiatric disorders, focusing on different sources of human genome variability, including SNPs and CNVs, which can affect not only coding genes but also RNA regulatory elements, such as miRNAs. First, we have interrogated different candidate genes for psychiatric disorders overlapping with known CNVs, finding 14 different genes variable in copy number in psychiatric disorders but not in control individuals. Then, narrowing the analysis on mood disorders, we explored GSK3β gene considering both SNPs and a partially overlapping CNV. The GSK3β promoter and intron 1 region was found significantly associated with an earlier onset of the major depressive disorder. Finally, we have found evidence possibly pointing to a precise post-transcriptional regulation of circadian rhythms by miRNAs in mood disorder patients. Concretely, a variant in the precursor form of miR-182 could play an important role in fine-tuning its target sites involved in the control of sleep/wake cycles. Overall, we have provided evidence of different types of genome variation on neuronal genes or miRNA regulatory regions that can potentially contribute to the development of psychiatric disorders.
En aquesta tesi hem estudiat elements genètics que podrien contribuir potencialment en la fisiopatologia dels trastorns psiquiàtrics, centrant-nos en diferents fonts de variabilitat genòmica humana, incloent els SNPs i els CNVs, els quals poden afectar no només a gens codificants sinó també a elements reguladors, com els miRNAs. Primer, vam interrogar diferents gens candidats per trastorns psiquiàtrics solapats amb CNVs coneguts, trobant que 14 gens eren variables en el número de còpia en pacients però no en individus controls. Després, restringint l'anàlisi a trastorns afectius, vam explorar el gen GSK3β considerant SNPs així com també un CNV que se solapa parcialment amb el gen. Vam trobar la regió del promotor i de l'intró 1 del gen GSK3β associada de manera significativa amb una inferior edat d'inici del trastorn de depressió major. Finalment, hem trobat evidències que possiblement indiquen una precisa regulació post-transcriptional dels ritmes circadians per miRNAs en pacients amb trastorns afectius. Concretament, una variant en la forma precursora del miR-182 podria jugar un paper important en la fina regulació dels seus gens diana implicats en el control dels cicles de son i vigília. En general, hem aportat evidències de què diferents tipus de variació genòmica en gens neuronals o regions reguladores com els miRNAs podrien contribuir potencialment en el desenvolupament de trastorns psiquiàtrics.

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26

Araújo, Ronyere Olegário de. "Desenvolvimento de um painel de marcadores SNP de baixa densidade e análise de desequilíbrio de ligação de polimorfismos em genes candidatos em bovinos da raça Girolando." reponame:Repositório Institucional da UnB, 2014. http://repositorio.unb.br/handle/10482/18666.

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Tese (doutorado)—Universidade de Brasília, Faculdade de Agronomia e Medicina Veterinária, 2014.
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Desenvolvimento de um painel de marcadores snp de baixa densidade e análise de desequilíbrio de ligação de polimorfismos em genes candidatos em bovinos da raça Girolando. Ronyere Olegário de Araújo e Alexandre Rodrigues Caetano – Pesquisador PhD, Embrapa Recursos Genéticos e Biotecnologia, Brasília/DF. A crescente evolução de tecnologias tornaram possível analisar o genoma de várias espécies, compreender suas funções dentro dos sistemas biológicos e, sobretudo, começar a entender os mecanismos que controlam as interações entre os genótipos e os efeitos ambientais que estão envolvidos com a expressão de características de interesse econômico. O objetivo deste trabalho foi desenvolver e validar um painel personalizado a partir de um ensaio de 384 marcadores SNP localizados em genes candidatos que afetam características de produção, doenças genéticas, e para controle de parentesco, em animais da raça Girolando. Um total de 576 animais foram testados com o painel de 384 SNPs. Os SNPs selecionados foram usados para construir um painel baseado na tecnologia GoldenGate®. Os dados brutos da genotipagem foram analisados com o Módulo de Genotipagem do programa GenomeStudio, V2010.1, utilizando parâmetros padrão para clusterização dos dados de cada SNP. Como critério de filtragem dos SNPs e das amostras foram adotados os parâmetros: Separação de Clusters, Frequência de Genotipagem e a Taxa de Genotipagem. Após aplicação destes critérios, o arquivo final ficou composto de 249 SNPs e 419 animais. Após aplicação dos critérios de filtragem, foi possível observar uma diminuição da proporção de SNPs polimórficos (53,4%). Deste painel, 72 e 47 SNPs, estavam localizados nos cromossomos BTA06 e BTA14, respectivamente, e foram utilizados para os estudos de desequilíbrio de ligação - DL (parâmetros D’ e r2) e construção de blocos de haplótipos. As estimativas dos valores de DL entre os SNPs variaram de moderada à baixa magnitude, entre si e entre os BTAs. Para o parâmetro D’, a menor estimativa foi obtida para o BTA15 (0,0954) e a maior para o BTA24 (0,5311). Por outro lado, o parâmetro r2 apresentou menor estimativa no BTA17 (0,0011) e a maior no BTA22 (0,0834). Observou-se na população estudada a existência de 32 haplótipos em seis regiões do BTA06, com frequências observadas variando de 0,011 a 0,970. O número de SNPs capturados (TagSNPs) no BTA6 variou de 2 a 4 entre as regiões estruturadas e a distância entre eles variou de 75 a 70.177 pb. Para o BTA14, a estimativa de DL revelou a existência de 13 haplótipos em 4 regiões deste cromossomo, com frequências observadas variando de 0,023 à 0,589. Em geral, o número de SNPs capturados entre as regiões estruturadas no BTA14 foi igual a 2 e a distância entre eles variou de 225 a 17.284 pb, o que reduz em 50% os esforços no processo de genotipagem para cada uma das regiões gênicas estruturadas. Os resultados deste trabalho permitiram a caracterização de estruturas de blocos de haplótipos, em regiões genômicas relacionados com características de interesse zootécnico em animais da raça Girolando e poderão ser utilizados em estudos de associação entre essas regiões com características produtivas. _______________________________________________________________________________________________ ABSTRACT
Development of a low density SNP marker panel and analysis of linkage disequilibrium of polymorphisms in candidate genes in Girolando cattle. Ronyere Olegário de Araújo and Alexandre Rodrigues Caetano – Research PhD, Embrapa Recursos Genéticos e Biotecnologia, Brasília/DF. Recent technological advances made it possible to analyze the genomes of several species, understand their function within biological systems, and above all allow for initial understanding of mechanisms that control interactions between genotypes and environmental effects that are involved in the expression of traits of economic interest. The objective of this study was to develop and validate a custom panel with 384 SNP markers located in candidate genes affecting production traits, genetic diseases, and that could be usef for paternity control in Girolando cattle. A total of 576 animals were tested with 384 SNP panel using GoldenGate® technology on a BeadExpress platform. Raw genotyping data were analyzed with the Genotyping Module in the GenomeStudio platform v2010.1 using standard parameters for clustering the data from each SNP. Data quality control and filtering was performed usingthe following parameters: Clusters separation, Genotyping Frequency and Genotyping Rate. After application of those criteria the final dataset was composed of 249 SNPs and 419 animals. After applying QC criteria, we observed a decrease in the proportion of polymorphic SNPs (53.4%). The panel contained 72 and 47 SNPs from chromosomes BTA06 and BTA14, respectively. Linkage disequilibrium studies - LD (parameter D' and r2) and construction of haplotype blocks were performed. Estimates of LD values between SNPs ranged from moderate to low magnitude among themselves and between BTAs. For the parameter D', the lowest estimate was obtained for the BTA15 (0.0954) and the highest estimated in BTA24 (0.5311). Conversely, r2 showed the lowest estimates in BTA17 (0.0011) and higher in BTA22 (0.0834). A total of 32 haplotypes in six regions of BTA06 with frequencies ranging from 0.011 to 0.970 were observed. The number of SNPs captured (TagSNPs) in BTA6 ranged from 2 to 4 between the structured regions and the distance between them ranged from 75 to 70177 pb. For BTA14, estimated LD revealed 13 haplotypes in four regions of the chromosome with observed frequencies ranging from 0.023 to 0.589. In general, the number of SNPs captured between the structured regions in BTA14 was equal to 2 (the own TagSNP and the adjacent SNP) and the distance between them ranged from 225 to 17284 pb, which could result in reductions of 50% in genotyping efforts for each gene structured regions. These results allowed the characterization of haplotype block structures in genomic regions related to traits of interest in Girolando cattle and will be useful for performing association studies between the characterized regions with production traits.

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27

Rodríguez, Huanca Francisco Halley. "Identificación de marcadores SNP (polimorfismo de nucleótido único) asociados a la resistencia frente al virus de la necrosis pancreática infecciosa (IPN) en truchas arcoíris (Oncorhynchus mykiss)." Tesis, Universidad de Chile, 2017. http://repositorio.uchile.cl/handle/2250/143702.

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Tesis para optar al Grado de Magíster en Ciencias Animales y Veterinarias.
La necrosis pancreática infecciosa (IPN) es una enfermedad viral con un impacto negativo considerable en la acuicultura de la trucha arcoíris (Oncorhynchus mykiss).. El objetivo del presente trabajo ha sido detectar las regiones genómicas que explican la resistencia al virus de la necrosis pancreática infecciosa (IPNV) en truchas arcoíris. Un total de 2.278 peces provenientes de 58 familias de medios hermanos y hermanos completos fueron desafiados con virus lPN para inducir la enfermedad. De estos fueron genotipados 768 peces: 488 resistentes y 280 susceptibles. Para el genotipado se utilizó un microarreglo Axiom®, Affymetrix® de 57 mil marcadores de tipo polimorfismo de nucleótido único (SNP). Se realizó un análisis de asociación de genoma completo utilizando los datos fenotípicos y genotípicos de los peces desafiados. Se utilizaron modelos de regresión lineal y regresión logística. La heredabilidad para la resistencia al virus IPN calculada con información de pedigrí para el rasgo tiempo de muerte fue 0,39 y para el rasgo de supervivencia binaria fue 0,32, y usando información genómica fue de 0,46 y 0,45, respectivamente. El análisis de asociación indicó que la resistencia al virus IPN es un rasgo Oligogénico. Se detectó un SNP asociado de forma significativa al rasgo tiempo de muerte en el cromosoma 5. La proporción de la varianza fenotípica y heredabilidad explicada por este marcador fue de 0,035 y 0,076, respectivamente. El Sentrin-specific protease 5 (SENP5) podría ser un gen candidato implicado en la resistencia frente a este patógeno por encontrarse en las cercanías del SNP significativo. Debido a la reducida proporción de la varianza fenotípica explicada por el marcador detectado, concluimos que la incorporación de toda la información genómica, a través de la selección genómica, podría ser el enfoque más adecuado para acelerar el progreso genético en el mejoramiento de la resistencia frente al virus IPN en trucha arcoíris.
Infectious pancreatic necrosis (IPN) is a viral disease with a considerable negative impact on rainbow trout aquaculture. The objective of the present work was to detect the genomic regions that explain the resistance to infectious pancreatic necrosis virus (IPNV) in rainbow trout (Oncorhynchus mykiss). A total of 2,278 fishes from 58 families of complete siblings were challenged with lPN virus to induce the disease. A total of 768 fishes, 488 resistant and 280 susceptible, were genotyped with an Axiom® microarray, Affymetrix® of 57,000 single nucleotide polymorphism (SNP) markers. A complete genome association analysis was performed using the phenotypic and genotypic data of the challenged fishes. Linear regression and logistic regression models were used. The heritability for IPN virus resistance calculated with pedigree information for time of death trait was 0.39 and for the binary survival trait was 0.32, and using genomic information was 0.46 and 0.45, respectively. Association analysis indicated that resistance to IPN virus is an oligogenic trait. A SNP was significantly associated with the day-of-death trait on chromosome 5. The proportion of the phenotypic variance and heritability explained by this marker was 0.035 and 0.076, respectively. Sentrin-specific protease 5 (SENP5) could be a candidate gene involved in resistance to this pathogen because it is found near to the significant SNP. Due to the reduced proportion of the phenotypic variance explained by the detected marker, we conclude that the incorporation of all genomic information, through genomic selection, could be the most appropriate approach to accelerate genetic progress in the improvement of resistance to IPN virus in rainbow trout.
Financiamiento: Proyecto CORFO-INNOVA (12PIE - 17669).

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Cournu-Rebeix, Isabelle. "Génétique de la sclérose en plaques : criblage anonyme du génome et gènes candidats." Paris 6, 2003. http://www.theses.fr/2003PA066074.

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De, Lucchi Chiara. "Improving key root traits in sugar beet: Fusarium resistance." Doctoral thesis, Università degli studi di Padova, 2016. http://hdl.handle.net/11577/3424410.

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The challenge of the twenty-first century is to produce enough food to meet population demands without extending land or damaging the environment. Combining a maximum number of desirable traits such disease resistance, greater yield, and high quality is a desirable goal for plant breeders. The development of resistant crop genotypes is essential to ensure global food security, make the plant more useful and avoid crop losses. The development of molecular markers linked to the target traits is needed to predict phenotypic variation based on genotype. Marker-Assisted Selection (MAS) can reduce costs and the time required to obtain new cultivars by comparing selection only based on phenotypic evaluation. Single nucleotide polymorphisms (SNPs) are widely used as genetic marker. Sugar beet (Beta vulgaris L.) is the second source of world sugar supply and is grown in all temperate zones. The crop is attacked by many pathogens and among these, the soil-borne fungus Fusarium oxysporum causes severe sugar beet damages. Two different formae speciales have been reported in sugar beet, F. oxysporum f. sp. betae that causes Fusarium yellows, and F. oxysporum f. sp. radicis-betae that causes Fusarium root rot. Disease symptoms are characterized by wilt and yellow leaves that normally die as the disease progresses. Internal symptoms consist of a brown or grey brown vascular discoloration and in the case of root rot, there is a back external rot in the primary root. Sugar beet varieties are susceptible to F. oxysporum, which can cause a lower root yield and reduce sugar quality. No genetic studies have been done up to now, so no genes or quantitative trait loci (QTLs) conferring resistance to F. oxysporum in sugar beet have been reported. The aims of this work were (i) to investigate the response of a wide collection of sugar beet lines to F. oxysporum f. sp. betae, (ii) to identify resistant lines suitable for future breeding efforts and (iii) to discover molecular markers linked to the Fusarium resistance that could be considered for use in marker-assisted selection (MAS) programs. The first part of the thesis is a literature review of sugar beet breeding achievements, including the discovery of monogermity and cytoplasmic-genetic male sterility (CMS) that allowed the release of hybrid varieties. The review also focused on the breeding progresses against diseases obtained with classical and molecular methods using sources of resistance from wild beets. Next-generation sequencing (NGS) technologies with the recent release of the full sugar beet genome sequence are also reported. Incorporation of genomics into conventional sugar beet breeding programs is essential to obtain important yield achievements in sugar beet. The second part was aimed at screening a wide range of sugar beet lines to identify the different effect to F. oxysporum f. sp. betae inoculation and to select resistant and susceptible lines. To achieve this, 29 sugar beet lines were screened under greenhouse conditions with two highly virulent isolates belonging to different genetic sub-groups. The third part regards an experiment conducted to evaluate the response of different sugar beet breeding germplasm to isolates of F. oxysporum f. sp. betae. In the previously tested lines, an unusual root rot was observed, normally reported in cases of infection with F. oxysporum f. sp. radicis-betae. Eight susceptible lines, from USDA-ARS (US) and UNIPD (University of Padova, Italy), were inoculated with three different isolates of F. oxysporum f. sp. betae, the causal agent of Fusarium yellows. All inoculated lines developed disease symptoms, but severe root rot was observed only in the susceptible UNIPD lines inoculated with isolates that had never caused root rot in the USDA germplasm. In this work, an unusual root rot was reported for the first time that seems to be caused not only by the isolates, but is also due to a germplasm effect. The fourth part was aimed to identify molecular SNP markers linked to the Fusarium resistance in sugar beet. A candidate gene approach was used on susceptible and resistant lines to achieve this goal. Five resistant gene analogues were screened by means of a high-resolution melting (HRM) analysis and two allelic variants, within two genes, were significantly associated to Fusarium resistance. Sanger sequencing allowed the discovery of two SNP markers linked to the resistance. These two SNPs were significantly associated with the resistance and were mapped on the exon of Bv7_171470_ojty and Bv2_043450_zhxk, respectively.
Il miglioramento genetico delle piante coltivate, basato sull’esplorazione, sull’utilizzo delle risorse genetiche e sulla ricerca genomica avanzata, è prioritario per soddisfare il fabbisogno alimentare di una popolazione mondiale in costante crescita. In particolare, l’introgressione di tratti desiderabili come la resistenza alle malattie e la maggior resa produttiva è fondamentale per garantire la sicurezza alimentare a livello globale. Per accelerare il miglioramento delle piante è essenziale predire le variazioni fenotipiche sviluppando marcatori molecolari legati ai tratti in esame. La selezione assistita da marcatori molecolari può ridurre costi e tempi di ottenimento di nuove varietà rispetto alla selezione basata solo su variazioni fenotipiche. Fra i marcatori molecolari disponibili, le mutazioni di singola base (SNP) sono i più diffusi. La barbabietola da zucchero (Beta vulgaris L.) è la seconda fonte di zucchero al mondo ed è coltivata in tutte le aree temperate. La coltura è colpita da numerosi patogeni e, fra questi, il fungo Fusarium oxysporum causa severi danni. Due differenti forme speciali di Fusarium, Fusarium oxysporum f. sp. betae (Fusarium yellows) e Fusarium oxysporum f. sp. radicis-betae (Fusarium root rot) sono state identificate in barbabietola. La malattia è caratterizzata da avvizzimento e clorosi fogliare con un progressivo deperimento delle foglie, spesso seguito dalla morte dell’intera pianta. I sintomi interni consistono in una discolorazione vascolare con imbrunimento dei fasci vascolari e, nel caso di marciume radicale, è presente un caratteristico annerimento all’esterno della radice principale. Per il controllo del patogeno, l’impiego di fungicidi e le rotazioni colturali non sono efficaci. L’introgressione di geni di resistenza dal germoplasma selvatico è ritenuta la strategia principale per la difesa della coltura. Questo richiede lo sviluppo di marcatori molecolari legati ai geni di resistenza per la selezione assistita degli individui resistenti. Gli obiettivi del lavoro di tesi sono stati i seguenti: (i) valutare la risposta a Fusarium oxysporum f. sp. betae di un’ampia collezione di linee di barbabietola da zucchero (ii) identificare linee resistenti a Fusarium oxysporum da poter utilizzare in futuri programmi di miglioramento genetico e (iii) identificare marcatori molecolari SNP (polimorfismi del DNA a singolo nucleotide) legati alla resistenza a Fusarium da utilizzare in programmi di selezione assistita da marcatori. Il primo contributo del lavoro di tesi descrive lo stato dell’arte dei risultati ottenuti nel miglioramento genetico della barbabietola da zucchero. Il contributo si focalizza sui progressi ottenuti nella resistenza a malattie con metodi di miglioramento genetici classico e con l’impiego di tecniche molecolari utilizzando come fonte di resistenza germoplasma selvatico. E’ stato inoltre considerato il contributo delle nuove tecnologie di sequenziamento e del recente rilascio del genoma di riferimento al miglioramento genetico della barbabietola. Il secondo contributo riguarda la valutazione della risposta a Fusarium oxysporum f. sp. betae di un’ampia collezione di linee di barbabietola da zucchero al fine di identificare linee resistenti e suscettibili. Per raggiungere questo scopo sono state esaminate 29 linee di barbabietola da zucchero. Le piante sono state infettate con due isolati fungini F19 e Fob220a, appartenenti a due gruppi genetici distinti, entrambi altamente patogenici. Dopo l’inoculo, per un periodo di sei settimane, è stato attribuito, per ciascuna pianta, un punteggio da 0 a 5 in base ai vari sintomi di malattia manifestati, quali: avvizzimento fogliare, clorosi e necrosi. Successivamente, le piante sono state raccolte e le radici sono state esaminate per vedere dove era presente marciume radicale, discolorazione e quali piante invece risultavano resistenti al patogeno. Il terzo contributo descrive la risposta di due diverse collezioni di germoplasma di barbabietola da zucchero a isolati di Fusarium oxysporum f. sp. betae. Linee suscettibili, provenienti da USDA-ARS (US) e UNIPD (Università di Padova, Italia), sono state inoculate con tre distinti isolati di Fusarium oxysporum f. sp. betae, l’agente causa di Fusarium yellows. Tutte le linee inoculate hanno sviluppato i sintomi della malattia, ma un grave marciume radicale è stato osservato solo nelle linee provenienti da UNIPD inoculate con isolati che non avevano mai causato marciume radicale nel germoplasma USDA. Il quarto contributo riguarda l’identificazione, su geni candidati, di marcatori molecolari SNPs associati alla resistenza alla malattia. In particolare, sono stati identificati 5 analoghi a geni di resistenza (RGA) dal lavoro di Dohm et al. 2014 e sono stati analizzati tramite analisi High Resolution Melting (HRM) su 96 campioni delle 6 linee più resistenti e più suscettibili a Fusarium. Due varianti, in 2 dei geni testati, sono risultate significativamente associate (p < 0.01) con la resistenza a Fusarium. Le varianti sono state validate attraverso sequenziamento Sanger. Il sequenziamento ha permesso di individuare due marcatori SNPs. L’associazione tra questi due SNPs e la resistenza a Fusarium è stata successivamente validata con il metodo di genotipizzazione Comparative allele-specific PCR (KASPar) su 96 campioni resistenti e 96 campioni suscettibili. La frequenza dell’allele A sia per lo SNP_Bv7_171470 e lo SNP_Bv2_043450 è risultata significativamente più alta negli individui resistenti rispetto a quelli suscettibili. Questi due SNPs potranno essere utilizzati in programmi di selezione genetica al fine di migliorare la resistenza a Fusarium in barbabietola da zucchero.

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Melo, Elisabete de. "Síndrome hepatopulmonar (SHP): estudo prospectivo para avaliar a progressão da hipoxemia em pacientes candidatos ao transplante de fígado." Faculdade de Medicina de São José do Rio Preto, 2006. http://bdtd.famerp.br/handle/tede/240.

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Hepatopulmonary syndrome (HPS), caused by abnormal intrapulmonary vasodilatation (IPVD), when associated with severe hypoxemia has been related to increased morbid-mortality in liver transplant candidates. The progression of hypoxemia in cirrhotic patients with IPVD is not well known. The aim of this study is to determine the probability of developing hypoxemia (Pa02 <70mmHg) in IPVD patients waiting for liver transplantation over two years. Thirty-two transplant candidates with IPVD detected by contrast-enhanced echocardiography (GI) were prospectively studied and the Pa02 of then was measured at the start and at the end of 12 and 24 months. Eleven patients without IPVD were taken as control group (GII). Paired t test showed that mean Pa02 was significantly lower at 24 months compared with basal mean at GI (78,5 ± 18,9 vs 94,05 ± 14,9; p=0,001). GI patients had significantly lower mean Pa02 at 12 months (84,6 ± 14,8 vs 95,7 ± 7,3; p=0,003) and at 24 months (78,5 ± 19,0 vs 88,7 ± 7,1; p=0,036) compared with GII patients. The Kaplan-Meier estimated ratio for the appearance of hypoxemia was approximately 10% ±5% at 12 months and 28% ± 10% at 2 years. The mean variation for Pa02 in GI patients was 4,6±13,4mmHg at 12 months and 15,5±15,5mmHg at the end of two years. There was no appearance of either hypoxemia or IPVD in GII patients. The variables: age, Child-Pugh score, smoking habit, pré-transplant Pa02 and PaC02 values did not discriminated patients who presented hypoxemia during the period of two years study. In conclusion, we demonstrate prospectively the progressive course of HPS, even on it s subclinical stage; the estimated risk for the appearance of hypoxemia in patients with IPVD was at least 30% at the end of 2 years. The identification of the early appearance of hypoxemia can lead to a better understanding of the hepatopulmonary syndrome natural history and may be helpful to optimize timing and to predict the outcomes of liver transplantation.
A síndrome hepatopulmonar (SHP) é causada por dilatação anormal da vasculatura intrapulmonar (DVP) em indivíduos com doença hepática, tendo como consequência graus variados de hipoxemia arterial. A hipoxemia grave aumenta a morbimortalidade em candidatos a transplante de fígado, e sua progressão na história natural da SHP não é bem conhecida. O objetivo deste estudo é determinar a probabilidade de desenvolvimento de hipoxemia (Pa02 <70mmHg) em pacientes com DVP em lista de espera para o transplante de fígado, em um período de dois anos. Foram estudados prospectivamente 32 pacientes com DVP (GI), detectada pela ecocardiografia com contraste e a Pa02 foi medida ao início, aos 12 e aos 24 meses do estudo. Como grupo controle (GII), foram incluídos 11 pacientes sem DVP. Os testes t de Student e exato de Fisher foram usados para comparação dos resultados. A curva de Kaplan-Meier foi empregada para verificar a probabilidade de hipoxemia nos dois grupos. A média da Pa02 aos 12 e 24 meses foi significativamente menor no GI quando comparada ao GII (84,6±14,8mmHg vs 95,7±7,3mmHg; p=0,003 e 78,5±19,0mmHg vs 88,7±7,1mmHg; p=0,036, respectivamente). No GI há evidência de que a média dos valores da Pa02 aos 24 meses é menor do que a média basal (78,5±18,9 vs 94,0±14,9; p=0,001). A razão estimada para o aparecimento da hipoxemia foi aproximadamente 10%±5% aos 12 meses e 28%±10% aos 24 meses (Curva Kaplan-Meier), para o GI. A média da variação da Pa02 no GI foi de 4,613,4mmHg aos 12 meses e de 15,515,5mmHg aos 24 meses. Nenhum paciente apresentou hipoxemia nem DVP no GII durante o período de estudo. Os parâmetros: idade, Child-Pugh, tabagismo, Pa02 e PaC02 iniciais, não identificaram os indivíduos com DVP que desenvolveram hipoxemia em dois anos de observação. Conclui-se que: Demonstramos o curso progressivo da SHP, mesmo em condições subclínicas; O risco estimado para hipoxemia em portadores de DVP foi de pelo menos 30% em dois anos; A identificação precoce do aparecimento da hipoxemia pode levar a um melhor entendimento da história natural da SHP e ser útil para a otimização da indicação do transplante de fígado e obtenção de melhores resultados.

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Veneroni, Gisele Batista. "Associação de SNPs em genes candidatos e de regiões cromossômicas com espessura de gordura subcutânea em bovinos da raça Canchim." Universidade Federal de São Carlos, 2010. https://repositorio.ufscar.br/handle/ufscar/5383.

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Universidade Federal de Minas Gerais
The Canchim has been used in beef cattle as an alternative to production intensification. Canchim (5/8 Charolais + 3/8 Zebu) and MA (offspring of Charolais bulls and 1/2 Canchim + 1/2 Zebu cows) constitute a synthetic beef cattle breed which has a good growth potential and tropical adaptation but suboptimal fat deposition under pasture. Backfat thickness (BF), total fat amount and distribution of fat have a strong impact on carcass and meat quality in beef cattle. For this reason, research has been conducted to increase fat deposition in this breed, including the search for molecular markers to identify animals with high genetic potential for fat deposition. To incorporate molecular genetics into breeding programs in beef cattle, it is essential that the association between molecular markers and production traits is evaluated in the population in which they are to be used. There are reports of many candidate genes and chromosomal segments associated with variation in fat deposition in cattle. The objective of this study was to identify SNPs associated to backfat thickness in Canchim. To achieve this objective we searched for SNPs in development and differentiation enhancing factor 1 and insulin-like growth factor binding protein 3 genes, tested the association of SNPs in the insulin-like growth factor binding protein 3, peroxisome proliferative active receptor gamma coactivator 1A, proteasome 26S subunit ATPase 1, development and differentiation enhancing factor 1, corticotropin releasing hormone and fatty acid binding protein 4 genes with fat thickness in Canchim and MA beef cattle. We also analyzed the existence of genomic regions associated with backfat thickness in these populations using a 54 K chip in extreme phenotypes. From the associated regions we selected the ones of BTA14 to validate the association by analysis of haplotypes in the whole population. The SNPs analyzed in development and differentiation enhancing factor 1 and fatty acid binding protein 4 genes were associated with variation in backfat thickness, wereas no association was found for the SNPs of the insulin-like growth factor binding protein 3, peroxisome proliferative active receptor gamma coactivator 1A, proteasome 26S subunit ATPase 1 and corticotropin releasing hormone genes. Additionally, two chromosomal regions of BTA14 were associated with the trait in this work.
A raça Canchim tem sido utilizada na bovinocultura de corte como alternativa de intensificação de produção. Grupos genéticos Canchim (5/8 Charolês + 3/8 Zebu) e MA (descendentes de touros Charoleses e de 1/2 Canchim + 1/2 Zebu) constituem essa raça sintética, que tem bom potencial de crescimento e adaptação tropical, mas deposita pouca gordura quando alimentada à pasto. Espessura de gordura subcutânea, quantidade e distribuição de gordura total têm grande impacto sobre a qualidade da carne e carcaça em gado de corte. Por este motivo, pesquisas têm sido realizadas com o objetivo de aumentar a deposição de gordura nessa raça, incluindo a busca por marcadores moleculares que auxiliem a identificação de animais com maior potencial genético para deposição de gordura. Para que a genética molecular possa ser incorporada nos programas de melhoramento de bovinos de corte, é essencial que a associação entre marcadores moleculares e características de produção seja avaliada na população em que se deseja utilizá-los. Há relatos de muitos genes candidatos e segmentos cromossômicos associados com a variação da deposição de gordura em bovinos. O objetivo desse trabalho foi identificar SNPs associados à deposição de gordura em animais da raça Canchim criados à pasto. Para tanto, foram prospectados SNPs nos genes do fator de aumento de desenvolvimento e de diferenciação 1 e proteína ligante ao fator de crescimento semelhante à insulina 3, verificada a a associação de SNPS presentes nos genes da proteína ligante do fator de crescimento semelhante à insulina 3, coativador de proliferação de peroxissomo ativo por receptor gama 1A, subunidade 26S ATPse do proteassomo, do fator de aumento de desenvolvimento e de diferenciação 1, hormônio liberador de corticotrofina e proteína ligante de ácido graxo 4 com espessura de gordura em animais Canchim e MA. Além disso, a existência de regiões genômicas associadas com espessura de gordura subcutânea foi investigada em populações Canchim e MA usando um chip de 54 K em fenótipos extremos. Dentre as regiões com associação significativa, foram eleitas aquelas presentes no BTA14 para validar a associação por análise de haplótipos na população toda. SNPs nos genes do fator de aumento de desenvolvimento e de diferenciação 1 e da proteína ligante de ácido graxo 4 foram associados à variação de espessura de gordura subcutânea, enquanto que nenhuma associação foi observada para os SNPs dos genes proteína ligante ao fator de crescimento 7 semelhante à insulina 3, coativador de proliferação de peroxissomo ativo por receptor gama 1A, subunidade 26S ATPse do proteassomo e hormônio liberador de corticotrofina. Também foram associadas com a característica avaliada nesse trabalho, duas regiões cromossômicas do BTA14.

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Barros, Monteiro Janice. "Déterminants génétiques de la résistance à l'insuline et du diabète sucré : exploration par SNP (single nucleotide polymorphism) de la calpai͏̈ne-10 et d'autres gènes candidats dans la population amazonienne du Brésil." Montpellier 1, 2004. http://www.theses.fr/2004MON1T016.

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L'IDENTIFICATION DES SNP (SINGLE NUCLEOTIDE POLYMORPHISM) DANS LE GENOME HUMAIN ET LA NOUVELLE UTILISATION DES CARTES GENETIQUES DENSES BASEES SUR DES SNP ET LE DESEQUILIBRE DE LIAISON DANS UNE POPULATION ONT APPORTE UN PROGRES REMARQUABLE DANS L'EXPLORATION DES GENES CANDIDATS POUR LES MALADIES COMPLEXES POLYGENIQUES ET MULTIFACTORIELLES. AFIN D'IDENTIFIER DES NOUVEAUX MODELES POPULATIONNELS POUR L'ETUDE DE LA GENETIQUE DE LA RESISTANCE A L'INSULINE OU DU DIABETE SUCRE, NOUS AVONS EXPLORE LES SNP ET LA STRUCTURE HAPLOTYPIQUE DE LA CALPAINE-10 (CLPN-10) DANS LA POPULATION D'AMAZONIE (BRESIL). CE GENE, LOCALISE SUR LE LOCUS CANDIDAT DU DIABETE DE TYPE 2 (DT2) DU Chr 2q37. 3, A ETE DECOUVERT DANS LA POPULATION DE MEXICAINS AMERICAINS (MIM 125853) ET, DEPUIS, LES RESULTATS D'ASSOCIATION GENETIQUE DANS D'AUTRES POPULATIONS SONT RESTES CONTRADICTOIRES. LA POPULATION AMAZONIENNE A ETE COMPOSEE DE SUJETS DE POIDS NORMAL, APPAREMMENT SAINS (n=44), DES SUJETS OBESES (n=77) OU ATTEINTS PAR DT2 (n=102). LE GENOTYPAGE DES SNP A ETE REALISE PAR SEQUENCAGE DE L'ADN GENOMIQUE (ABI 373 A), LA DIGESTION ENZYMATIQUE DES PRODUITS PCR ALLELE- SPECIFIQUE OU LA MS-PCR (MUTAGENICALLY SEPARATED-PCR). LES HAPLOTYPES COMPLEXES ONT ETE RECONSTRUITS DANS LA POPULATION PAR LE PROGRAMME PHASE ALORS QUE L'ASSOCIATION GENETIQUE ET LA CORRELATION GENOTYPE/PHENOTYPE ONT ETE TESTEES RESPECTIVEMENT PAR REGRESSION LOGISTIQUE OU ANOVA. UN PREMIER TRAVAIL A EU COMME BUT DE COMPARER LES HAPLOTYPES DE LA CLPN10 DANS LES POPULATIONS AMAZONIENNE (MANAUS) ET D'EXTRACTION EUROPEENNE (MONTPELLIER). LE CRIBLAGE DE 5 SNP, UCSNP -45 (a/c), -44 (c/t), -43 (g/a), -19 (3/2) ET -63 (c/t), A PERMIS LA RECONSTRUCTION DE 15 HAPLOTYPES DANS LES DEUX POPULATIONS. L'HAPLOTYPE ANCESTRAL AFRICAIN h2, (CORRESPONDANT A L'HAPLOGROUPE 112 DECRIT CHEZ LES MEXICAINS AMERICAINS) A ETE PREVALENT DANS LA POPULATION AMAZONIENNE PAR RAPPORT AUX EUROPEENS (P < 0. 0001), MAIS A DES FREQUENCES ALLELIQUES EQUIVALENTES (q=0. 15 et 0. 17) ENTRE LES POPULATIONS DECLAREES NOIRES ET L'ENSEMBLE DE LA POPULATION METISSEE (MULLATOS) BRESILIENNE. CET HAPLOTYPE h2 A ETE ASSOCIE A L'OBESITE, ALORS QUE DEUX AUTRES HAPLOTYPES (h9 ET h3) SE SONT MONTRES PROTECTEURS. UN AUTRE HAPLOTYPE PATHOGENE (h6), PLUS PREVALENT DANS LA POPULATION NOIRE, A ETE ASSOCIE A L'INTOLERANCE GLUCIDIQUE. BASE SUR CES DONNEES, UN DEUXIEME TRAVAIL A EU COMME OBJECTIF D'EXPLORER L'ASSOCIATION POSSIBLE AU DT2. UN GROUPE DE 102 PATIENTS AVEC DT2 A ETE COMPARE A UN GROUPE TEMOIN (n=93) AVEC DES DEGRES COMPARABLES D'OBESITE. LA POPULATION ATTEINTE PAR DT2 A ETE CARACTERISEE PAR UNE FAIBLE PREVALENCE DE L'HAPLOTYPE h2 (P < 0. 0001), UNE AUGMENTATION DE LA PREVALENCE DE L'HAPLOTYPE h3 (D'ORIGINE EUROPEENNE) ET h9, AINSI QUE PAR UNE PLUS HAUTE PREVALENCE DE L'HAPLOTYPE h6 (P < 0. 05). CES RESULATS SUGGERENT QUE LES HAPLOTYPES DE CE GENE ONT UNE IMPORTANTE VALEUR DIAGNOSTIQUE POUR L'OBESITE OU LE DT2 MAIS QUE CE LOCUS (CLPN10) PRESENTE UNE FORTE COMPOSANTE GEOGRAPHIQUE ET DIVERSITE ETHNIQUE. LA COMPOSITION ETHNIQUE D'UNE POPULATION OU LES DONNEES DEMOGRAPHIQUES APPARAISSENT COMME D'IMPORTANTS DETERMINANTS POUR L'ETUDE D'ASSOCIATION GENETIQUE DANS LES MALADIES COMPLEXES. LA POPULATION D'AMAZONIE, ISSUE D'UN MELANGE DIRECTIONNEL ENTRE LES POPULATIONS NATIVES AMERINDIENNES ET EUROPEENNES (NOTAMMENT PORTUGAISES) AINSI QUE L'ADDITION DES POPULATIONS AFRICAINES ENTRE LE 16e ET 19e SIECLE, PEUT REPRESENTER UN MODELE EXCEPTIONNEL D'ETUDE GENETIQUE DU DIABETE SUCRE OU DE L'OBESITE, AYANT DES CONSEQUENCES NON SEULEMENT SUR LA COMPREHENSION DE DETERMINANTS GENETIQUES DE CES DEUX AFFECTIONS FREQUENTES, MAIS EGALEMENT SUR L'ETAT DE SANTE DE CETTE REGION DU BRESIL QUI COMME D'AUTRES POPULATIONS DU MONDE SE TROUVE EXPOSEE AU RISQUE CROISSANT DE MALADIES METABOLIQUES ET CARDIOVASCULAIRES.

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Souza, Manuela Barbosa Rodrigues de. "Análise genética de novos potenciais polimorfismos de risco em Transtornos do Humor e utilização de abordagens computacionais em busca de genes candidatos a Doença de Alzheimer." Universidade Federal de Pernambuco, 2013. https://repositorio.ufpe.br/handle/123456789/13412.

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FACEPE
Doenças neuropsiquiátricas afetam cerca de 450 milhões de pessoas em todo mundo e dentre estas patologias os Transtornos do Humor (TH) e Doença de Alzheimer (DA) são as mais comuns. Em relação à sua etiologia as doenças neuropsiquiátricas são resultados de variações em um grupo de genes e de fatores ambientais. Pesquisas recentes vêm mostrando associação positiva entre variações genéticas em genes envolvidos nos sistemas de neurotransmissores com o desenvolvimento de doenças neuropsiquiátricas. Por isso, os estudos sobre polimorfismos genéticos, nas doenças psiquiátricas são de grande importância para a compreensão dos mecanismos moleculares envolvidos e podem auxiliar no diagnóstico das mesmas. Neste cenário, mutações encontradas no DNA têm sido amplamente estudadas, a fim de elucidar aspectos genéticos relacionados às neuropatologias. Os polimorfismos do tipo SNPs (Polimorfismo de Base Única) e INDELs (inserções e deleções de fragmentos de DNA) têm se destacado devido as fortes associações com os TH e DA. Diversos métodos de biologia molecular têm sido utilizados para detectar estes tipos de polimorfismos, os experimentos moleculares geram grande quantidade de dados a serem analisados, fazendo-se necessário a utilização de ferramentas computacionais para se extrair informações a partir desses dados gerados. Assim, o objetivo desse estudo foi o uso de bioinformática e de genotipagem em larga escala na busca de novos polimorfismos genético em TH e aplicação de ferramentas computacionais em banco de dados de GWAS referente à DA. Para obter os resultados referentes à TH optamos por utilizar o software CLCbio Workbench®, sequenciamento automatizado mega Bace 1000 e experimentos preliminares da técnica de DNA pooling. Já para a DA, utilizamos o teste de associação e método de regressão linear do software PLINK e o pacote genetics da linguagem de programação R, para correlacionar os níveis da proteína βamiloide no plasma e líquido cefalorraquidiano e um total de 598.821 SNPs, ambos os dados oriundos do banco de dados ADNI (Alzheimer’s Disease Neuroimaging Initiative). Após uma sequência de passos in silico identificamos variações anteriormente descritas e novos polimorfismos candidatos à fisiopatologia dos TH, na fase de validação dessas variações, por meio de sequenciamento, falsos positivos foram frequentemente identificados, sendo descartados após a verificação na cadeia complementar. Apenas o SNP rs14068, localizado no exon 2 do gene GABRA5 foi validado em amostras de pacientes com TH. No estudo referente à DA, 5 SNPs nas regiões dos genes TOMM40, PAMR1, TRIM9 e CCDC112 e 3 SNPs em regiões de intron atingiram associação significativa, levantando a possibilidade de estejam relacionados a fisiopatologia da DA.

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34

Johnson, Andrew Danner. "Search for functional alleles in the human genome with focus on cardiovascular disease candidate genes." Columbus, Ohio : Ohio State University, 2007. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1187018497.

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Gill, Jennifer. "Assessment of genetic markers for the improvement of beef quality and consistency." Thesis, University of Edinburgh, 2010. http://hdl.handle.net/1842/4711.

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The overall aim of this thesis was to investigate the genetic control of beef quality in a commercial population of Aberdeen Angus-sired cattle with a view to trait improvement. The population studied included 500 Angus-cross animals, all with purebred Aberdeen Angus sires, from a selection of farms throughout Scotland. A number of carcass-related weight traits and taste panel assessed sensory traits were measured on these animals. A population of 265 Charolais cross cattle (all with purebred sires) was then used to explore the extrapolation of results across breeds. The first aim of this thesis was to investigate heritabilities for important carcass and meat quality traits and to assess the quality of a number of taste-panel derived meat quality traits by calculating three consistency statistics. Consistency statistics (parameter range 0 to 1) for the taste panel traits were moderately high, particularly for panel member consistency and reproducibility, with values ranging from 0.48 to 0.81 and 0.43 to 0.73, respectively. Estimated heritabilities were low for most of the sensory taste-panel-evaluated traits, where the maximum value was 0.16 for overall liking, but were higher for carcass traits where carcass weight heritability was 0.7. To perform these analyses it was first necessary to confirm paternity using a number of genetic markers. Therefore, a comparison of the power of both microsatellite and SNP markers for paternity exclusion was carried out to determine the more effective method. Results indicated that approximately three times as many SNP markers than microsatellite markers were required for parentage exclusion, and a panel of 15 microsatellite markers was used to assign paternity before subsequent data analysis was carried out. The remaining aims of this thesis centred on exploring genetic markers for carcass and meat quality. Firstly, the Angus animals were genotyped for the del11 myostatin mutation which was found to be segregating at a relatively low frequency (0.04) and was shown to be associated with a 17.4 kg increase in carcass weight (P < 0.05) in the heterozygous animals when compared to the homozygous wild-type animals. By analysing the haplotype associated with the mutant allele, it was determined that there have been at least two separate introductions of the mutant allele into the Aberdeen Angus breed. A number of SNPs were also tested for their effects on the carcass and meat quality traits in the Angus animals. The SNPs fell into two groups: eight that have been incorporated into commercially available tests and a further 28 from alternative candidate genes that have effects in different breeds and species. In total, 17 SNPs significantly affected at least one of the traits measured. Of these significant associations, a number have been seen previously, such as the association between calpain and tenderness (P = 0.01) and growth hormone and eye muscle area (P = 0.05), and some of which were novel, such as the association between growth hormone receptor and steak odour (P = 0.02) and corticotrophin releasing hormone and gristle distance from fat (P = 0.004). A further six SNPs, identified by resequencing of the malic enzyme 1 (ME1) and small heterodimer partner (SHP) genes, were tested for their effects on the traits measured in this thesis. Five of the SNPs, including one which caused a non-synonymous amino acid change, had a significant effect on at least one of the traits tested including fat class (P = 0.002), eye muscle area (P = 0.01), sirloin weight before maturation (P = 0.03), sirloin steak tail length (P = 0.004) and juiciness (P = 0.004) where the effect sizes were 1.79 units, 565 mm2, 0.36 kg, 17.12 mm and 0.23 taste panel units, respectively. To assess the effect of the genotyped SNPs on intramuscular fat (IMF), a simple method of visible IMF quantification in the sirloin steak was developed using digital photographs and an image analysis program. Results showed that two SNPs in the calpain gene, known to be linked with an increase in meat tenderness, were associated with an increase in visible IMF% and the del11 mutation was associated with a reduction in visible IMF%. The heritabilities, SNP association validations and novel SNP-trait associations identified in this thesis provide tools for use in breeding programs, possibly via marker assisted selection to improve meat quality traits. However, the results seem breed-specific, as most of the significant effects were not replicated in the Charolais population.

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Mekbib, SB, TJC Regnier, and L. Korsten. "Efficacy and mode of action of yeast antagonists for control of Penicillium digitatum in oranges." Tropical Plant Pathology, 2011. http://encore.tut.ac.za/iii/cpro/DigitalItemViewPage.external?sp=1000688.

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Three yeast antagonists (two strains of Cryptococcus laurentii and one of Candida sake) from orange trees reduced incidence of green mold by 80 to 95% when tested in wounded orange fruits inoculated with Penicillium digitatum and incubated at 7ºC for 30 days. The yeasts inhibited conidial germination of the pathogen, but did not kill the spores. Effectiveness of the three yeasts as antagonists was associated in part with their ability to rapidly colonize wound sites, despite low nutrient availability. Observations suggested that production of extracellular matrix by the yeasts may have facilitated rapid wound colonization. Germination of P. digitatum conidia was significantly inhibited when the pathogen and antagonists were in direct physical contact in a culture suspension. The results supported the view that competition for nutrients is also a mode of action of yeasts against P. digitatum.

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Naderi, Darbaghshahi Saeid [Verfasser]. "Exploring the potential of machine learning methods and selection signature analyses for the estimation of genomic breeding values, the estimation of SNP effects and the identification of possible candidate genes in dairy cattle / Saeid Naderi Darbaghshahi." Gießen : Universitätsbibliothek, 2019. http://d-nb.info/1177678365/34.

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Oussalah, Abderrahim. "Déterminants génétiques du métabolisme des monocarbones : approche gène candidat dans deux populations ambulatoires et étude d'association avec la maladie de Crohn." Thesis, Nancy 1, 2011. http://www.theses.fr/2011NAN10088/document.

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Des études d'associations pangénomiques ont démontré une relation entre le taux plasmatique de la vitamine B12 et le polymorphisme du gène FUT2 (fucosyltransferase 2). Dans des modèles expérimentaux, le statut sécréteur pour FUT2 a été impliqué dans la susceptibilité à l'infection par Helicobacter pylori (H. pylori). Nous avons évalué l'influence du polymorphisme FUT2 461 G>A sur les marqueurs du métabolisme des monocarbones dans deux populations ambulatoires en Europe et en Afrique de l'Ouest ainsi que la possible association entre l'infection par H. pylori et le polymorphisme de FUT2. Nous avons mis en évidence une influence de FUT2 461 G>A sur le taux plasmatique de la vitamine B12 mais n'avons pas retrouvé d'influence du statut sérologique pour H. pylori sur cette association, du moins chez les sujets ambulatoires en Europe et en Afrique de l'Ouest. L'hyperhomocystéinémie est un marqueur de carence en donneurs de méthyle. Plusieurs travaux ont évalué le taux plasmatique de l'homocystéine au cours des maladies inflammatoires chroniques de l'intestin (MICI) et ont abouti à des résultats mitigés. Par ailleurs, l'ampleur de l'association entre le métabolisme de l'homocystéine et les MICI reste méconnue. Nous avons réalisé une méta-analyse afin : (i) d'évaluer l'association entre le métabolisme de l'homocystéine et les MICI et (ii) d'étudier le risque de thrombose lié à l'hyperhomocystéinémie au cours des MICI. Le risque d'hyperhomocystéinémie était significativement plus élevé chez les patients avec une MICI en comparaison aux sujets contrôles. L'évaluation du risque de thrombose associé à l'hyperhomocystéinémie au cours des MICI requiert des études complémentaires. Un statut carencé en folates était associé à un impact plus fort du polymorphisme MTHFR C677T sur le risque primaire de MICI. L'hyperhomocystéinémie et plusieurs polymorphismes sur les gènes du métabolisme des monocarbones sont associés au risque primaire et à la sévérité de la maladie de Crohn (MC). L'hyperhomocystéinémie augmente l'activité de la superoxyde dismutase (SOD), un marqueur fiable et validé du stress oxydatif. A l'aide d'un SNP array Illumina exhaustif du métabolisme des monocarbones, nous avons (i) étudié les déterminants génétiques (single nucleotide polymorphisms, SNPs) associés au taux plasmatique de l'homocystéine et de la SOD chez des patients suivis pour une MC et (ii) recherché les SNPs associés à l'âge du diagnostic de la MC. Deux SNPs étaient indépendamment associés au taux plasmatique de l'homocystéine (MTHFR, AHCY). Cinq SNPs étaient indépendamment associés au taux plasmatique de la SOD. Parmi ces cinq SNPs, trois sont liés à la vitamine B12 (FUT2, CUBN, et TCN2), un aux folates (GGH), et un dernier à la synthèse cellulaire de l'homocystéine (AHCY). Par ailleurs, nous avons mis en évidence deux SNPs associés à un âge précoce du diagnostic de la MC (CHDH, ABCB1)
Genome wide association studies demonstrated an association between plasma vitamin B12 and FUT2 (fucosyltransferase 2). It has been suggested that the association between FUT2 and low plasma vitamin B12 level may be the consequence of an increased susceptibility to Helicobacter pylori (H. pylori) infection. We evaluated the association between FUT2 461G>A polymorphism and vitamin B12 and investigated whether the influence of FUT2 on H. pylori serology is part of the mechanisms that underlie this association, in two populations from Europe and West Africa. In this study we confirmed the influence of FUT2 461 G>A polymorphism on plasma vitamin B12 level and found no influence of H. pylori serological status on this association, at least in ambulatory subjects from Europe and West Africa. The magnitude of the association between homocysteine metabolism and inflammatory bowel diseases (IBD) is unknown while the association between hyperhomocysteinemia and thrombosis remains controversial in IBD. We conducted a systematic review of the literature and performed a meta-analysis to examine these issues. The risk of hyperhomocysteinemia is significantly higher in IBD patients when compared to controls. The risk assessment of hyperhomocysteinemia-related thrombosis in IBD requires further investigation. Deficient folate status is associated with a higher impact of MTHFR C677T polymorphism on IBD risk. Hyperhomocysteinemia and several gene variants of one-carbon metabolism are associated with the occurrence and severity of Crohn's disease (CD). Hyperhomocysteinemia results in part from methyl donors deficiency - which is frequent in patients with CD - and increases the activity of superoxide dismutase (SOD), a validated and reliable marker of oxidative stress. We designed a 384-plex GoldenGate oligo pool assay for the comprehensive one-carbon metabolism genotyping using Illumina platform. The aims of this study were (i) to assess genetic determinants of plasma homocysteine and superoxide dismutase (SOD) levels in patients with IBD and (ii) to look for single nucleotide polymorphisms (SNPs) associated with age at CD onset. Two SNPs were associated with plasma homocysteine level (MTHFR, AHCY). Five SNPs were independently associated with plasma SOD level. Of these five SNPs, three are related to vitamin B12 (FUT2, CUBN, and TCN2), one is related to folate (GGH), and the last one to homocysteine (AHCY). In addition, we identified two SNPs associated with early CD onset (CHDH, ABCB1)

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Avogbé, Patrice Hodonou. "Déterminants génétiques de la réparation d'ADN et du métabolisme des monocarbones : approche gènes candidats et études d'association avec le risque de carcinome hépatocellulaire et le cancer du poumon." Thesis, Université de Lorraine, 2012. http://www.theses.fr/2012LORR0201/document.

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Mondialement, le carcinome hépatocellulaire (CHC) et le cancer du poumon (CP) constituent un problème majeur de santé publique. Plusieurs études d'association gène candidat ont montré que les SNPs de gènes candidats à la réparation d'ADN et au métabolisme des monocarbones (MMC) influencent le risque de CHC et CP. Toutefois, aucune étude n'a évalué, de façon exhaustive, l'influence des SNPs de la réparation d'ADN ou du MMC avec le risque de CP ou de CHC. Notre étude vise à identifier - à l'aide de deux SNP array de 384 SNPs - les polymorphismes génétiques de la réparation d'ADN et du MMC qui sont prédictifs du risque de CHC chez des Caucasiens cirrhotiques. Nous avons aussi recherché les déterminants génétiques de la réparation d'ADN associés au risque de CP. Nos résultats ont montré que six SNPs du gène BRIP1 (BRCA1interacting protein C?terminal helicase ; rs4986763, rs4986764, rs1557720, rs4986765, rs2191248, et rs11871785) étaient significativement associés au risque de CHC chez les patients porteurs d'une cirrhose d'étiologie virale selon le modèle génétique additif. Après correction de "False Discovery Rate", BRIP1 rs4986764 et rs1557720 étaient significativement associés au risque de CHC. Deux SNPs du MMC situés sur GGH (rs11545076 et rs11545077) étaient significativement associés au risque de CHC chez les patients porteurs d'une cirrhose d'étiologie non virale. Par ailleurs, seul le polymorphisme POLL rs3730477 était associé à un risque accru de CP dans le modèle génétique récessif. La dernière partie de notre étude était consacrée à l'analyse comparée d'hémogrammes et des dommages d'ADN chez des conducteurs de taxi-moto (CTM) de Cotonou - exposés à l?air pollué par le benzène et les HAPs -, et les témoins non exposés. Nos résultats ont montré une réduction significative du nombre des globules blancs, lymphocytes, neutrophiles et plaquettes, avec une misincorporation accrue d'uracile, de 8 oxodG et la présence d'un adduit majeur d'ADN chez les CTM par rapport aux témoins. En conclusion, nous avons identifié six variants sur BRIP1 et deux variants sur GGH associés au risque de CHC sur une cirrhose d'étiologie virale et non virale, respectivement. De plus, nous avons montré que POLL rs3730477 est un prédicteur significatif du risque de cancer du poumon. Une validation de ces résultats dans des cohortes indépendantes s'avère indispensable
Worldwide, hepatocellular carcinoma (HCC) and lung cancer (LC) represent a major public health problem. Previous studies reported associations between single nucleotide polymorphisms (SNPs) in DNA repair or monocarbon metabolism (MCM) genes and LC or HCC risk. However, influences of these SNPs on LC or HCC risk have not been comprehensively evaluated. Our study aimed to identify potential interesting DNA repair and MCM gene variants associated with HCC risk in cirrhotic Caucasians. To this end, we used the Illumina's GoldenGate® technology and performed a comprehensive investigation of 384 SNPs on 94 DNA repair genes and 384 SNPs on 77 MCM genes. This comprehensive SNP-array fine mapping approach was also used to identify potential interesting DNA repair gene variants associated with susceptibility to LC in Caucasians. Our results showed that six variants on BRIP1 gene (BRCA1 interacting protein C-terminal helicase: rs4986763, rs4986764, rs1557720, rs4986765, rs2191248, and rs11871785) were significantly associated with HCC risk in patients carrying hepatitis virus-associated cirrhosis under an additive genetic model. After false discovery rate (FDR) correction for multiple testing, BRIP1 rs4986764 and rs1557720 displayed statistically significant associations with HCC risk. Two SNPs on GGH gene were associated with HCC risk in patients carrying non viral cirrhosis. In our study, only POLL rs3730477 was associated with an increased LC risk under a recessive genetic model (OR=2.81, 95% CI 1.51?5.24). Lastly, we evaluated hematologic changes and levels of DNA adducts, 8-oxodG, dU, and m5dC in Cotonou's motorbike taxi drivers (MBTD) - exposed to air pollution by benzene and polycyclic aromatic hydrocarbons (PAHs) - compared to unexposed controls. Compared to controls, MBTD displayed a significant decrease in the number of white blood cells, lymphocytes, neutrophils and platelets, with the formation of an unknow DNA adduct, whereas uracil misincorporation and 8-oxodG levels in DNA were significantly increased. In conclusion, we identified six variants on BRIP1 gene and two variants on GGH gene that are associated with susceptibility to HCC. In addition, POLL rs3730477 variant was associated with susceptibility to LC. Replication of these findings in independent cohorts is warranted

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Pönisch, Roman. "Isolierung, Identifizierung und funktionelle Charakterisierung der Metallo-Aminopeptidase CaApe2 — Ein experimenteller Beitrag zur Beurteilung des kariogenen Potentials von Candida albicans." Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2009. http://nbn-resolving.de/urn:nbn:de:bsz:14-ds-1230898959618-82212.

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Die Hefe Candida albicans ist ein fakultativ humanpathogener Mikroorganismus, der insbesondere bei immungeschwächten Patienten schwere Erkrankungen der Haut und Schleimhäute sowie der inneren Organe hervorrufen kann. Seit langer Zeit wird eine Beteiligung des Hefepilzes an der Ätiopathogenese der Zahnkaries diskutiert, vor allem aufgrund der Säure-bildung, die zur Demineralisation der Zahnhartsubstanz beitragen kann. Hydrolytische Enzyme ermöglichen vermutlich die Gewebeinvasion von Candida albicans. In der vorliegenden Arbeit wurde ein sezerniertes peptidolytisches Enzym aus der Zellwand des Mikroorganismus isoliert, identifiziert und funktionell charakterisiert. Die mittels massenspektrometrischer Analyse der tryptischen Peptide und Datenbankrecherche ermittelte Primärstruktur und die Ergebnisse der funktionellen Charakterisierung ließen eine Identifi-zierung des peptidolytischen Enzyms als neutrale Arginin/Alanin/Leucin-spaltende Metallo-Aminopeptidase (CaApe2) zu, die durch den ORF CaO19.5197 (GenBank RefSeq XM 705313) kodiert wird. Mithilfe der Proteinanalytik wurde Serin-88 als N-terminale Aminosäure ermittelt. Die Aminosäuren 88 bis 954 des hypothetischen Genprodukts ergeben eine nominale Molekularmasse von 97,607 kDa. CaApe2 weist gleich hohe Ähnlichkeit mit den paralogen Genprodukten ScAap1 und ScApe2 auf, was eine Duplikation und Subfunktionalisierung des phylogenetischen Vorläufergens in Saccharomyces cerevisiae nahe legt. Die fehlende kollagenolytische Wirksamkeit von CaApe2 spricht gegen eine direkte Rolle des Enzyms in der Pathogenese der Dentinkaries von Candida albicans, schließt aber eine unterstützende Funktion nicht aus. Die Kollagendegradation durch aufgeschlossene Zellen und Kulturüberstand einer Flüssigkultur von Candida albicans wurde im sauren und neutralen Milieu mithilfe der Hydroxyprolin-Bestimmung untersucht. Dabei war keine Kollagenolyse mit Aktivitätsmaximum im neutralen Bereich nachweisbar. Im sauren pH-Bereich konnte eine deutliche Hydrolyse von säureunlöslichem Typ-I-Kollagen und auch von demineralisierter Dentinmatrix durch Kulturmedium gezeigt werden. Diese Kollagenolyse kann auf die bereits umfangreich charakterisierten sezernierten Aspartylproteinasen zurückgeführt werden. Die in der Literatur beschriebene Korrelation zwischen dem Ausmaß des Kariesbefalls und der Quantität der Besiedelung mit Candida albicans legt eine Beteiligung des Hefepilzes an der Kariogenese nahe. Auch die in der vorliegenden Arbeit gezeigte Fähigkeit von Candida albicans zur Dentinkollagendegradation unterstützt die Hypothese einer Kariogenität der Hefe
The proteolytic potential of the pathogenic fungus Candida albicans was evaluated by the identification and functional characterization of a peptidolytic enzyme isolated from the cell wall of the microorganism. Determination of basic structural and kinetic data identified a neutral arginine/alanine/leucine-specific metallo-aminopeptidase of unknown function termed CaApe2 which is encoded by ORF CaO19.5197 (GenBank RefSeq XM_705313). Mass spectrometric tryptic peptide analysis and N-terminal protein sequencing revealed serine-88 to represent the N-terminus of CaApe2. The isolated CaApe2 protein shares equally high similarity with the gene products ScAap1 and ScApe2 suggesting duplication of a phylogenetically ancient precursor gene in Saccharomyces cerevisiae. The observed failure to cleave human type-I and type-IV collagen in vitro challenges a direct role secreted CaApe2 might play in the degradation of extracellular matrix components during host colonization, but does not exclude per se a contribution of the aminopeptidase to the pathogenicity of C. albicans

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41

Semlin, Lydia. "Vergleichende Bewertung vom Typ der Hemmer der sekretorischen Aspartatproteinasen (Sap) im Candida-Keratinozyten-Adhärenz Assay und im Hautkonstrukt gestützten Modell der lokalisierten Kandidose." Diss., Ludwig-Maximilians-Universität München, 2013. http://nbn-resolving.de/urn:nbn:de:bvb:19-157851.

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42

Pönisch, Roman. "Isolierung, Identifizierung und funktionelle Charakterisierung der Metallo-Aminopeptidase CaApe2 — Ein experimenteller Beitrag zur Beurteilung des kariogenen Potentials von Candida albicans." Doctoral thesis, Technische Universität Dresden, 2008. https://tud.qucosa.de/id/qucosa%3A23915.

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Die Hefe Candida albicans ist ein fakultativ humanpathogener Mikroorganismus, der insbesondere bei immungeschwächten Patienten schwere Erkrankungen der Haut und Schleimhäute sowie der inneren Organe hervorrufen kann. Seit langer Zeit wird eine Beteiligung des Hefepilzes an der Ätiopathogenese der Zahnkaries diskutiert, vor allem aufgrund der Säure-bildung, die zur Demineralisation der Zahnhartsubstanz beitragen kann. Hydrolytische Enzyme ermöglichen vermutlich die Gewebeinvasion von Candida albicans. In der vorliegenden Arbeit wurde ein sezerniertes peptidolytisches Enzym aus der Zellwand des Mikroorganismus isoliert, identifiziert und funktionell charakterisiert. Die mittels massenspektrometrischer Analyse der tryptischen Peptide und Datenbankrecherche ermittelte Primärstruktur und die Ergebnisse der funktionellen Charakterisierung ließen eine Identifi-zierung des peptidolytischen Enzyms als neutrale Arginin/Alanin/Leucin-spaltende Metallo-Aminopeptidase (CaApe2) zu, die durch den ORF CaO19.5197 (GenBank RefSeq XM 705313) kodiert wird. Mithilfe der Proteinanalytik wurde Serin-88 als N-terminale Aminosäure ermittelt. Die Aminosäuren 88 bis 954 des hypothetischen Genprodukts ergeben eine nominale Molekularmasse von 97,607 kDa. CaApe2 weist gleich hohe Ähnlichkeit mit den paralogen Genprodukten ScAap1 und ScApe2 auf, was eine Duplikation und Subfunktionalisierung des phylogenetischen Vorläufergens in Saccharomyces cerevisiae nahe legt. Die fehlende kollagenolytische Wirksamkeit von CaApe2 spricht gegen eine direkte Rolle des Enzyms in der Pathogenese der Dentinkaries von Candida albicans, schließt aber eine unterstützende Funktion nicht aus. Die Kollagendegradation durch aufgeschlossene Zellen und Kulturüberstand einer Flüssigkultur von Candida albicans wurde im sauren und neutralen Milieu mithilfe der Hydroxyprolin-Bestimmung untersucht. Dabei war keine Kollagenolyse mit Aktivitätsmaximum im neutralen Bereich nachweisbar. Im sauren pH-Bereich konnte eine deutliche Hydrolyse von säureunlöslichem Typ-I-Kollagen und auch von demineralisierter Dentinmatrix durch Kulturmedium gezeigt werden. Diese Kollagenolyse kann auf die bereits umfangreich charakterisierten sezernierten Aspartylproteinasen zurückgeführt werden. Die in der Literatur beschriebene Korrelation zwischen dem Ausmaß des Kariesbefalls und der Quantität der Besiedelung mit Candida albicans legt eine Beteiligung des Hefepilzes an der Kariogenese nahe. Auch die in der vorliegenden Arbeit gezeigte Fähigkeit von Candida albicans zur Dentinkollagendegradation unterstützt die Hypothese einer Kariogenität der Hefe.
The proteolytic potential of the pathogenic fungus Candida albicans was evaluated by the identification and functional characterization of a peptidolytic enzyme isolated from the cell wall of the microorganism. Determination of basic structural and kinetic data identified a neutral arginine/alanine/leucine-specific metallo-aminopeptidase of unknown function termed CaApe2 which is encoded by ORF CaO19.5197 (GenBank RefSeq XM_705313). Mass spectrometric tryptic peptide analysis and N-terminal protein sequencing revealed serine-88 to represent the N-terminus of CaApe2. The isolated CaApe2 protein shares equally high similarity with the gene products ScAap1 and ScApe2 suggesting duplication of a phylogenetically ancient precursor gene in Saccharomyces cerevisiae. The observed failure to cleave human type-I and type-IV collagen in vitro challenges a direct role secreted CaApe2 might play in the degradation of extracellular matrix components during host colonization, but does not exclude per se a contribution of the aminopeptidase to the pathogenicity of C. albicans.

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43

Semlin, Lydia [Verfasser], and Claudia [Akademischer Betreuer] Borelli. "Vergleichende Bewertung vom Typ der Hemmer der sekretorischen Aspartatproteinasen (Sap) im Candida-Keratinozyten-Adhärenz Assay und im Hautkonstrukt gestützten Modell der lokalisierten Kandidose / Lydia Semlin. Betreuer: Claudia Borelli." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2013. http://d-nb.info/1036836797/34.

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44

Muiños, Gimeno Margarita. "Analysis of genetic variation in microrna-mediated regulation and the susceptibility to anxiety disorders." Doctoral thesis, Universitat Pompeu Fabra, 2009. http://hdl.handle.net/10803/7192.

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We have investigated genetic variation in microRNA-mediated regulation as a susceptibility factor for anxiety disorders following two different approaches. We first studied two isoforms of the candidate gene NTRK3 by re-sequencing its different 3'UTRs in patients with Panic (PD) and Obsessive Compulsive disorders (OCD) as well as controls. Two rare variants that altered microRNA-mediated regulation were identified in PD. Conversely, association of a common SNP with OCD hoarding subtype was found. Moreover, we have also studied a possible involvement of microRNAs in anxiety disorders. Consequently, we have analysed the genomic organisation and genetic variation of miRNA-containing regions to construct a panel of SNPs for association analysis. Case-control studies revealed several associations. However, it is worth remarking the associations of miR-22 and miR-488 with PD; two microRNAs for which functional assays and transcriptome analysis after microRNA overexpression showed significant repression of a subset of genes involved in physiological pathways linked to PD development.
Hem investigat la variació genètica a la regulació mediada per microRNAs com a factors de susceptibilitat pels trastorns d'ansietat seguint dues aproximacions diferents. Primer vam estudiar dues isoformes del gen candidat NTRK3 mitjançant la reseqüenciació dels seus diferents 3'UTRs a pacients de pànic (TP), a pacients amb trastorn obsessiu compulsiu (TOC) i a controls. Dues variants rares que alteren la regulació mediada per microRNAs foren identificades per TP. D'altra banda, es trobà associació d'un SNP comú amb el subtipus acumulador de TOC. A més, també hem estudiat la possible implicació dels microRNAs als trastorns d'ansietat. Conseqüentment, hem analitzat l'organització genòmica i la variació genètica a regions que contenen microRNAs per construir un panell d'SNPs per fer anàlisis d'associació. Els estudis cas-control van revelar algunes associacions. Tanmateix, val la pena destacar les associacions del miR-22 i el miR-488 amb TP; dos microRNAs pels quals assajos funcionals i anàlisis de transcriptoma després de la seva sobreexpressió han mostrat una repressió significativa d'un grup de gens implicats en vies fisiològiques lligades al desenvolupament del TP.

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45

Fonseca, Casals Francina. "Pharmacogenomic study of oppioid addicts in methadone treatment / Francina Fonseca Casals." Doctoral thesis, Universitat Pompeu Fabra, 2010. http://hdl.handle.net/10803/7234.

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Although the well established efficacy of methadone maintenance treatment (MMT) in the opioid dependence disorder, there is a group of patients that are poor responders. The study of the influence of methadone pharmacodynamics and pharmacokinetics in dose requirements and program outcome remains still controversial. The aim of this dissertation is to study the pharmacodynamic and pharmacokinetic factors involved in the methadone maintenance treatment efficacy.
The study recruited opioid dependence patients (DSM-IV criteria) from a MMT community program. Patients were clinically assessed and blood samples were obtained in order to evaluate methadone plasma concentrations of (R,S)-, (R) and (S)- methadone. Allelic variants of genes encoding the following proteins were assessed: BDNF, OPRM1, MYOCD, mGluR6, mGluR8, CRY1, NR4A2, 1q31.2 (rs965972), 2q21.2 (rs1867898), CYP3A5, CYP2D6, CYP2B6, CYP2C9, CYP2C19 and P-glycoprotein. Responders and non-responders were defined by means of illicit opioid consumption detected in random urinalyses.
Differences in response status were found depending on different single nucleotide polymorphisms (SNPs of genes encoding for BDNF, MYOCD and GRM6. The CYP2D6 metabolizing phenotype was associated with response to MMT, and also with methadone dosage requirement and methadone plasma concentrations.
Els programes de manteniment amb metadona (PMM) han demostrat eficàcia en el tractament del trastorn per dependència d'opiacis malgrat la persistència de pacients amb mala resposta al tractament. L'estudi dels factors farmacodinàmics i farmacocinètics implicats en la resposta terapèutica ofereix resultats controvertits. L'objectiu de la tesi doctoral que es presenta és estudiar els factors farmacodinàmics i farmacocinètics de la metadona que poden estar implicats en l'eficàcia del tractament. S'han inclòs pacients ambulatoris diagnosticats de trastorn per dependència d'opiacis (segons criteris DSM-IV) en PMM. Els pacients s'han avaluat a nivell clínic i s'han obtingut mostres de sang per a l'estudi de les concentracions plasmàtiques de (R,S)-, (R) i (S)- metadona. S'han estudiat també les variants al·lèliques dels gens que codifiquen per: BDNF, OPRM1, MYOCD, mGluR6, mGluR8, CRY1, NR4A2, 1q31.2 (rs965972), 2q21.2 (rs1867898), CYP3A5, CYP2D6, CYP2B6, CYP2C9, CYP2C19 i P-glicoproteïna. La mostra s'ha dividit en responedors i no responedors en funció del nombre de controls d'orina positius per a heroïna en analítiques realitzades de forma aleatòria.
Es van detectar diferències en resposta al tractament segons les variants dels gens codificants per a BDNF, MYOCD i GRM6. També es va detectar una associació entre el fenotip de CYP2D6, la resposta al tractament, la dosi requerida de metadona i les concentracions plasmàtiques.

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46

Nwafor, Chinedu Charles. "Genetic investigation of seed development in grapevine." Doctoral thesis, 2015. http://hdl.handle.net/10449/33760.

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In a comprehensive attempt to understand the molecular and cellular processes driving seedlessness in grapevine, a seeded variety (wild-type) and its seedless somatic variant (mutant) were characterized at the morphological, genomic and transcriptomic levels in relation to berry development and seed content. The overall importance of clonal variability and the application of Next Generation Sequencing technology in highlighting the molecular events during seed formation within a developing berry have been clearly demonstrated. In this thesis three hypothesis were formulated, tested and confirmed. First it was hypothesized that the mutant has a gross morphology identical to the wild-type except for berry size and seed content. In testing this hypothesis quantitative and qualitative traits that relate to berry development and seed content were compared in the two clones. Here traits that were significantly different in the two lines are those that relate only to berry size and seed content. This evaluation was performed both in control conditions (self-pollination) and after anther/stigma removal which allowed the investigation of a possible role for parthenocarpy, stenospermocarpy or other mechanisms in promoting the phenotype of the seedless somatic variant. The second hypothesis states that the mutant is sterile or partly sterile hence cannot produce viable seeds. In order to verify this hypothesis pollen germination and viability assays were carried out in both clones. The tests confirmed pollen germination and vitality percentage of the mutant was significantly lower than that of the wild-type. The third hypothesis concerned the existence of genomic/transcriptomic differences between the two lines and could be tested through the power of the Next generation Sequencing technology. In particular, we raised the following questions. Are there somatic mutations that can allow the wild-type and mutant to be distinguished? What are the temporal and spatial changes that could occur in their respective transcriptomes? Especially how does expression levels of key regulatory genes change before, during and after fertilization in the two clones? These key questions were addressed with the aid of Molecular marker analysis, Array based SNP genotyping method and RNA-Seq approach. Using 58 microsatellites, the analyzed loci showed identical profile in the wild-type and the mutant. The 20K grapevine Illumina Chip revealed 16333 identical SNP loci in the two clones, thus a further confirmation of the true identity of the seedless line. Conversely variant calling from RNA-Seq enabled the identification of several somatic mutations at the whole-genome level in the two lines. At the same time, RNA-Seq allowed the creation of inventories of gene expression at successive stages of seed formation. i.e. stages E-L 15 (single flowers in compact groups), E-L 27 (young berries enlarging) and E-L 38 (berries harvest-ripe). Here the transcriptomes revealed by Illumina mRNA-Seq technology had approximately 98% of grapevine annotated transcripts and about 80% of them were commonly expressed in the two lines. Differential gene expression analysis revealed a total of 1075 differentially expressed genes (DE) in the pairwise comparison of developmental stages, which included DE genes specific to the wild-type background, DE genes specific to the mutant background and DE genes commonly shared in both backgrounds. The analysis of differential expression patterns and functional category enrichment of wild-type and mutant DE genes highlighted significant coordination and enrichment of pollen and ovule developmental pathways. The expression of some selected DE genes was further confirmed by real-time RT-PCR analysis. To the best of our knowledge the work presented in this thesis represents the most comprehensive attempt to characterize the genetic bases of seed formation in grapevine. We have shown that a seeded wine grape and its seedless somatic variant are similar in several biological processes except for berry size and seed content. With a high throughput method we could identify an inventory of genes with altered expression in the mutant compared to the wild-type, which may be responsible for the seedless phenotype. The genes located within known genomic regions regulating seed content may be used for the development of molecular tools to assist table grape breeding. Therefore the data reported here have provided a rich genomic resource for practical use and functional characterization of the genes that potentially underpin seedlessness in grapevine.

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47

Eyendja, christian. "Bases génétiques de la sténose valvulaire aortique calcifiée." Thèse, 2010. http://hdl.handle.net/1866/6041.

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La sténose valvulaire aortique (SVA) est une valvulopathie résultant en l'ouverture incomplète de la valve aortique. La calcification des feuillets associée au vieillissement est la cause la plus importante de la SVA. Sa pathogénèse implique des dépôts de lipoprotéines, de l'inflammation et de la calcification des feuillets. Notre étude vise à identifier les gènes associés à une prédisposition à la SVA afin de mieux comprendre les mécanismes sous-jacents à cette maladie et potentiellement identifier de nouvelles cibles thérapeutiques. Pour ce faire, nous avons recruté 190 patients avec SVA dégénérative et 192 témoins, appariés pour l'âge et le sexe, puis effectué une étude d’association par gènes candidats en utilisant des marqueurs génétiques polymorphiques (SNP). Les gènes candidats choisis incluent (1) ceux dont les polymorphismes ont été présumés associés à la SVA dans des études antérieures (APOB, APOE, ESR1, PTH et VDR) (2) des gènes dont les polymorphismes ont été significativement associés et validés pour quelques maladies inflammatoires (IL-10, TNFAIP3) ou pour le métabolisme lipidique (PCSK9, LDLR) dans des études d’association pangénomiques, et (3) des gènes impliqués dans la pathogénie de la SVA à partir d’études faites sur des modèles animaux en lien avec la calcification (BMP2, CCR5, CTGF, LRP5, MSX2, WNT3), le remodelage tissulaire (CTSS, MMP9) ou le métabolisme lipidique (SMPD1). Pour les gènes des groupes (1) et (2), nous avons utilisé les SNPs rapportés dans la littérature comme étant significativement associés. Pour le groupe (3), nous avons effectué une approche par «tagSNP» qui consiste à sélectionner un groupe de SNP capturant la variabilité génétique dans la région ciblée. Au total, 81 SNPs dans 18 gènes ont été testés. Nous avons trouvé une association nominale avec les gènes BMP2 (OR = 1.55, IC95%: 1.14-2.10, p = 0.004) et LRP5 (OR = 1.47, IC95%: 1.06-2.03, p = 0.023) après ajustement pour la maladie coronarienne. Les gènes BMP2 et LRP5, impliqués dans la calcification selon certains modèles expérimentaux, sont donc associés à la SVA. Ce travail devrait être validé dans une cohorte indépendante plus large dans un avenir rapproché et il pourrait être étendu à d’autres gènes.
Aortic valve stenosis (AVS) is a valvular heart disease caused by calcification leading to incomplete opening of the aortic valve. Calcification of valve leaflets associated with aging is the most common cause of AVS. AVS pathogenesis involves lipoprotein deposits, chronic inflammation and calcification of the aortic valve leaflets. Our study aims to identify genes associated with AVS in order to better understand its mechanisms and potentially identify new therapeutic targets. We recruited 190 cases with AVS of different severity and 192 controls matched for age and sex. Then we conducted a candidate gene association study using single nucleotide polymorphisms (SNPs). The candidate genes selected include: (1) those with polymorphisms putatively implicated in previous genetic association studies of AVS (APOB, APOE, ESR1, PTH and VDR); (2) those with validated associations to inflammatory diseases (IL-10, TNFAIP3) or lipid metabolism (LDLR ,PCSK9) in genome-wide association studies and, (3) genes impliated in AVS pathogenesis from studies with animal models and thought to be involved in calcification (BMP2, CCR5, CTGF, LRP5, MXS2, WNT3); tissue remodeling (CTSS, MMP9) or lipid metabolism (SMPD1). For the first two categories of genes, we tested the SNPs reported to be associated in the literature and, in the third category we used a tag-SNP approach which consists of selecting a subset of SNPs to capture variability in the target region. Finally, 81 SNPs in 18 genes were tested. We found a nominal association of BMP2 (OR=1.55, CI: 1.14 – 2.10, p=0.004) and LRP5 (OR=1.47, CI: 1.06 – 2.03, p=0.023) with presence of AVS after adjustment for coronary heart disease. The genes BMP2 and LRP5, which are known to be involved in calcification based on animal models, are associated with AVS. The result of the current study should be validated in a larger independent cohort in the near future and then, it could also be extended to the study of other genes.

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48

Lin, Ya-Ping, and 林亞平. "Development of Genome-Wide High-Density SNP Markers in Solanum pimpinellifolium and Investigation of Candidate Loci of Stamen Length in Tomato." Thesis, 2019. http://ndltd.ncl.edu.tw/handle/qxcg77.

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博士
國立臺灣大學
農藝學研究所
107
Botanists have been fascinated by the genetic mechanism of heterostyly since Darwin’s theory of evolution. It was believed that the genes controlling self-incompatibility and floral morphology were linked tightly, so-called S-locus. According to the classical evolutionary studies, when a plant evolved from outcrossing to selfing, it was necessary to lose self-incompatibility and then adjusted the positions of male and female floral organs through the rare recombination within the S-locus. However, new evidence suggested that homostyly resulted from hemizygote rather than the rare recombination. In agriculture, studying the genetic mechanism of self-incompatibility and heterostyly can understand the changes of crop genomes under the selection forces during domestication processes. Additionally, it can accelerate the production of hybrid seeds or ensure the pollination to increase yield. Solanum pimpinellifolium is a wild tomato originated from the coastal region of Peru and Ecuador. It serves as an important germplasm in tomato breeding programs because it displays many resistant traits and can freely cross to cultivated tomatoes. Previous studies classified this species as complete or near complete allogamy, complete autogamy and intermediate type based on its mating system. In addition, allogamous accessions displayed higher genetic diversity and more exsertion of stigma than autogamous ones. Because S. pimpinellifolium contains the variations of outcrossing rate and floral morphology within its own species, it could be an ideal material to study the genetic mechanism of self-incompatibility and heterostyly. Nowadays, molecular markers have been applied to crop breeding extensively. Accompanying by the cost down of next generation sequencing, the development of genome-wide high-density markers for germplasm becomes essential in breeding programs. In this research, we performed the PstI-digested associated DNA sequencing for 99 accessions of S. pimpinellifolium, resulting in 24,330 SNPs. The coverage extended to 12,790 genes, and a total of 7,383 genes were targeted directly by 16,365 SNPs. Besides, the sequencing regions and the annotated genes presented similar distributions through each chromosome. This suggested that PstI-digested associated DNA sequencing was an appropriate strategy to investigate candidate genes. This collection was divided into three subpopulations of single-ancestral genome and four subpopulations of mix-ancestral genome by ADMIXTURE. Principle component analysis, pairwise Fst and AMOVA all supported the subpopulations, implying this set of high-density markers was capable to estimate the subpopulations stably. Moreover, the overall LD decay was within 18 Kb, suggesting a fine resolution in genome-wide association study even to a single-gene level. However, to achieve such fine resolution, at least 50,000 markers were required. Three candidate loci controlling stamen length were identified via the mixed linear model in genome-wide association study of 98 S. pimpinellifolium accessions, but all three loci presented high false discovery rate. Since the power and false positive rate of genome-wide association study depend on the sample size of a studying population, we suggest two approaches to increase sample size. One is to increasing samples in each subpopulation evenly. This approach can potentially make rare alleles to common alleles by increasing the allele frequency. The other is to sampling more individuals in the northern Peru because the accessions in the northern Peru present more genetic diversity. This approach can also increase both rare alleles and common alleles. On the other hand, following the previous studies, stamen2.2 and stamen2.3 were located in the downstream interval next to style2.1. We performed a RNA sequencing experiment of M82 and TA3178. TA3178 is an introgression line of M82 and contains a segment of Solanum pennellii near style2.1. We identified this introgression region by comparing the difference of SNPs between these two lines. Afterwards, following the previous work in our team, we screened 18 candidate genes from marker cLED19A24 to CT9 by comparing the fold change and cDNA polymorphism between M82 and TA3178. This result suggested that Solyc02g087960.2, Solyc02g087970.1 and Solyc02g088070.2 should be the candidates of stamen2.2 and stamen2.3.

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49

LO, PRESTI Anna Rita. "CANDIDATE GENE ASSOCIATION ANALYSIS IN RESPIRATORY DISEASES – THE GEIRD PROJECT." Doctoral thesis, 2012. http://hdl.handle.net/11562/393934.

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L' Asma, la Rinite e la Bronco-pneumopatia cronica ostruttiva (BPCO) sono malattie respiratorie comuni in tutto il mondo, caratterizzate da infiammazione cronica locale e sistemica delle vie aeree e da aumentata reattività bronchiale, che contribuiscono in modo sostanziale alla morbilità e mortalità negli adulti dei paesi occidentali. Sono malattie complesse ed eterogenee derivate dall'interazione di fattori genetici ed ambientali. Diversi geni, ciascuno con un piccolo effetto, sono verosimilmente coinvolti nello sviluppo di queste malattie e possono contribuire alla variabilità del fenotipo in relazione all’ esposizione ambientale. Molti geni sono riportati in letteratura in associazione ad una, due o tutte e tre le malattie, sebbene i risultati di questi studi non sempre sono consistenti. Questo lavoro è parte del progetto GEIRD (Gene Environment Interaction Respiratory Diseases), uno studio di popolazione caso-controllo, che ha lo scopo di chiarire il ruolo dei fattori genetici ed ambientali in sviluppo, persistenza, gravità e controllo delle malattie infiammatorie. In particolare, la tesi di dottorato qui presentata si focalizza su uno studio di associazione di geni candidati in un' ampia e ben caratterizzata popolazione di soggetti italiani, allo scopo di identificare geni di suscettibilità ad asma, rinite e BPCO e geni di suscettibilità che possono essere comuni alle tre patologie. Un totale di 1175 soggetti, comprendenti soggetti affetti da Asma, Rinite e BPCO (casi) e soggetti non affetti da malattie infiammatorie delle vie aeree (controlli) sono stai arruolati nello studio. E' stata creata una banca di DNA di questi soggetti coinvolti. I geni candidati per lo studio sono stati scelti sulla base dei dati di letteratura, considerando studi di singoli geni, GWAS (studi di scansione sull’ intero genoma) e meta-analisi. È stato selezionato un gruppo di 69 geni coinvolti in processi biologici potenzialmente correlati con le patologie oggetto dello studio, quali l'infiammazione, l'immunità innata, l' immuno-regolazione, lo stress ossidativo, il metabolismo degli xenobiotici, la regolazione dell' equilibrio proteasi-antiproteasi e il rimodellamento tissutale. Un pannello di 384 “Tag-SNP”, rappresentative dei geni candidati oggetto dello studio, è stato sviluppato per l’ analisi con il sistema di genotipizzazione multipla GoldenGate (Illumina). È stato effettuato uno studio di associazione a singolo locus e a loci multipli per valutare l'associazione con i seguenti fenotipi: asma corrente, asma passato, asma totale, asma atopico corrente, rinite allergica e non allergica, rinite totale, e presenza di sintomi respiratori cronici. Una associazione statisticamente significativa (p<0,01) è stata osservata fra il gene IL-13(5q31) e l’ asma passato, i geni SPINK-5 (5q31-q32) e GSTP-1 (11q13) e la rinite non atopica, il gene NOS-1 (12q24.2) e la presenza di sintomi respiratori cronici. Un dato interessante che è emerso da questo studio è la presenza di associazione di polimorfismi nel gene IL1RL-2 (2q12) con più fenotipi (asma corrente, asma atopico corrente, presenza di sintomi respiratori cronici, rinite non allergica, e rinite totale) suggerendo un possibile ruolo di questo gene in tutte le patologie respiratorie studiate. È stato approfondito lo studio per questi geni mediante un’ analisi di associazione degli aplotipi. Questo ulteriore studio ha confermato le associazioni trovate nell’ analisi a singolo locus e il coinvolgimento dei geni IL-13, SPINK-5, GSTP-1, NOS-1 e IL1RL-2 nella suscettibilità alle malattie respiratorie infiammatorie. I risultati di questo studio potranno essere utilizzati in futuro per lo sviluppo di nuovi test genetici molecolari per l’identificazione precoce di sottogruppi di pazienti che necessitano di terapie specifiche o che hanno una suscettibilità individuale a specifici fattori di rischio ambientale mediante la determinazione del loro profilo di rischio genetico. Nell’era post-genomica, la ricerca e l’identificazione dei geni associati alle malattie complesse sono ancora una delle principali sfide per la comprensione profonda delle malattie umane complesse. Una migliore conoscenza dei meccanismi patogenetici e l'identificazione di marcatori molecolari di malattia e di profili genomici associati a particolari manifestazioni della malattia e al decorso clinico, offrirà nuovi bersagli per la terapia farmacologica e aprirà la strada a possibili applicazioni future per il trattamento e la prevenzione delle malattie, per mezzo di una definizione più accurata della prognosi e dello sviluppo di terapie più specifiche o addirittura individuali.
Asthma, Rhinitis and Chronic Obstructive Pulmonary Disease (COPD) are common respiratory diseases worldwide, characterized by systemic and local chronic inflammation of the airways and increasing bronchial responsiveness, that contribute substantially to morbidity and mortality in adults living in the developed world. They are complex and heterogeneous diseases resulting from interaction between genetic and environmental factors. Several genes, each with a small effect, are likely involved in the development of these diseases and might contribute to the phenotype variability according to environmental exposure. Many candidate genes are reported in the literature data in association to one, two or all three diseases, even if results of these studies are not always consistent. This work is a part of the GEIRD (Gene Environment Interaction Respiratory Diseases) project, a population-based case-control study, aimed to elucidate the role of environment and genetic factors in the occurrence, persistence, severity and control of inflammatory airway diseases. In particular, the PhD thesis project here presented is focused on candidate gene association analysis in a large and accurately defined series of Italian subjects, in order to identify genes involved in the susceptibility to Asthma, Rhinitis and COPD and susceptibility genes that may be common to all the three diseases. A total of 1175 individuals, including subjects affected by asthma, rhinitis and COPD (cases) and unaffected by airways inflammatory diseases (controls), have been enrolled. A DNA bank, from all the subjects participating to the study, was created. Candidate genes for the study was chosen on the basis of the analysis of literature data, considering single genes studies, GWAS and meta-analyses. A group of 69 genes, involved in pathways related to the all three studied diseases, as inflammation, innate immunity and immunoregulation, oxidative stress and metabolism of xenobiotics, regulation of the protease-antiprotease equilibrium, and tissue remodelling, were selected. A panel of 384 Tag SNPs, representative of the candidate genes, was genotyped by a customized multiplexed GoldenGate Genotyping assay (Illumina). A single-locus and multi-locus association analysis was conducted to evaluate association with the following phenotypes: current asthma, past asthma, total asthma (current and past), current atopic asthma, allergic rhinitis, non allergic rhinitis, total rhinitis (allergic and non allergic), and subjects presenting with chronic respiratory symptoms. A significant association (p<0,01) was observed between IL-13 (5q31) and past asthma, both SPINK-5 (5q31-q32) and GSTP-1 (11q13) and non-atopic rhinitis, NOS-1 (12q24.2-24.31) and chronic respiratory symptoms. More interestingly, polymorphisms in IL1RL-2 gene (2q12) were found associated to multiple phenotypes (current asthma, current atopic asthma, chronic respiratory symptoms, non atopic rhinitis, and total rhinitis) suggesting a possible role for this gene in all the studied respiratory diseases. Therefore, we decide to deepen the study performing an haplotype association analysis for these genes. This additional study confirmed the single-locus associations found and the involvement of IL-13, SPINK-5, GSTP-1, NOS-1 and IL1RL-2 genes in the susceptibility to inflammatory respiratory diseases. The results of this study can be used in the future for the development of new molecular genetic tests for the early identification of subgroups of patients who need a specific therapy or having an individual susceptibility to specific environmental risk factors, by the determination of their genetic risk profile. In the post-genomic era, searching and identification of genes associated with complex diseases are still one of the main challenges for dissecting human complex diseases. A better understanding of pathogenic mechanisms and the identification of molecular markers of disease and genomic profiles, associated to particular diseases phenotypes and clinical outcomes, will be offering new targets for pharmacological therapy and will be opening the way to possible future applications in disease treatment and prevention, by a more accurate prognosis determination and a more specific or even individual therapies.

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Hadjigol, S. "Evidence for natural selection acting on genes affecting lignin and cellulose biosynthesis in Eucalyptus globulus." Thesis, 2012. https://eprints.utas.edu.au/12930/2/Whole_thesis_030112.pdf.

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Eucalyptus globulus (Myrtaceae) is a forest tree species that is native to South-eastern Australia, including the island of Tasmania. It is the main eucalypt species grown in pulpwood plantations in temperate regions of the world and is being domesticated in many breeding programs. The improvement of its wood properties is a major objective of these breeding programs. As many wood properties are expensive to assess, there is increasing interest in the application of molecular breeding approaches targeting candidate genes, particularly those in the lignin and cellulose biosynthesis pathways. To assist in the identification of genes and allelic variants likely to have important phenotypic effects, this study aimed to determine whether there was a signature in the genome indicating that natural selection had caused differentiation amongst the races of E. globulus in candidate genes for wood properties. Differentiation among races based on single nucleotide polymorphisms (SNPs) within candidate genes was compared to differentiation based on microsatellite (SSR) markers. The rationale behind this approach is that if the differentiation observed in the gene-related SNPs was significantly different from that based on putatively selectively neutral markers, then this is evidence that selection maybe affecting the candidate gene. In order to do this, the genetic affinities within E. globulus (368 trees representing 42 localities partitioned into eight races from across the natural range of the species) were studied using 30 gene-based SNPs and 18 neutral nuclear SSR markers. STRUCTURE analysis based on these SSR markers showed that individuals fell into two distinctive groups (lineages). One group comprised individuals from King Island and mainland races from the Otways and Strzelecki Ranges; the second group comprised all the Tasmanian races plus the Furneaux Islands. The pattern of differentiation between races found using the neutral SSR markers was similar to that found previously, although the average FST was lower than in previous studies (FST = 0.05; 95% CI 0.041-0.063). The SNP dataset (98 SNPs from 20 genes) from the same set of samples was provided by Dr. Saravanan Thavamanikumar of the University of Melbourne. Twenty-four SNPs were excluded because their minor alleles were too rare (total minor allele frequency < 10%), also eight SNPs that were not in Hardy-Weinberg Equilibrium (HWE) were eliminated. A further 36 were excluded because positive linkage disequilibrium (LD) between SNPs within genes was found in at least one of the races. While virtually no LD was found between SNPs in some genes, the LD level varied markedly between races and between genes. Of the 30 SNPs included in the analysis, the FST values of most were within the 1-99% inter-percentile range observed for the SSR data, and the average FST (0.09; 95% CI 0.058-0.133) was not significantly different. However, 6 SNPs had FST values that were higher than the upper 99% percentile of the FST distribution for SSRs. The SNPs exhibiting signals of selection occurred in two candidate genes in the lignin (4CL; LIM) and three in cellulose (KOR – 2 SNPs; SUSY3) biosynthetic pathways and in one in a Protein kinase-like gene (PKL1). This suggests that natural selection has promoted adaptive differentiation between races and is congruent with quantitative genetic analysis of wood chemicals (cellulose and lignin content and S:G ratio of lignin) which have also been found to vary more between races than expected by chance. Despite evidence for selection acting on several SNPs, similar groupings of individuals were obtained from STRUCTURE analysis with both data sets.

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