Introdução: A vitamina D tem ações pleiotrópicas em muitas doenças crônicas. A expressão do receptor da vitamina D (VDR - vitamin D receptor) em diversas células do sistema imune reforça a possível influência da vitamina D nas doenças autoimunes. Polimorfismos genéticos localizados no gene VDR podem determinar alterações nos mecanismos de ação da vitamina D, porém com resultados ainda pouco conhecidos. O polimorfismo BsmI do gene VDR foi associado com lúpus eritematoso sistêmico (LES) em pacientes asiáticos. Estudos com pacientes lúpicos no Brasil ainda não foram realizados. Objetivos: Investigar a possibilidade dos polimorfismos BsmI e FokI do gene VDR aumentarem o risco para o desenvolvimento do LES e avaliar a possível associação destes polimorfismos com manifestações clínicas e laboratoriais da doença. Determinar os níveis séricos da 25-hidroxivitamina D [25(OH)D)] nos pacientes e investigar a possível associação das suas concentrações com os polimorfismos estudados e expressões clínicas e laboratoriais do LES. Materiais e métodos: Estudo caso-controle envolvendo 195 pacientes com LES e 201 controles saudáveis da mesma área geográfica. Foram pesquisados os polimorfismos BsmI e FokI do gene VDR. Os níveis séricos da 25(OH)D foram dosados nos casos. A genotipagem foi realizada por Restriction Fragment Length Polymorphism-Polimerase Chain Reaction (RFLP-PCR), usando primers e enzimas de restrição específicas para cada polimorfismo. A dosagem da 25(OH)D foi realizada por quimioluminescência. Os dados clínicos e laboratoriais foram coletados dos prontuários. Resultados: Não houve diferença estatisticamente significativa nas frequências genotípicas e alélicas dos polimorfismos BsmI e FokI entre casos e controles eurodescendentes. Não houve associação entre as manifestações clínicas e laboratoriais do LES e os polimorfismos estudados. Os níveis séricos médios da 25(OH)D foram de 25,51±11,43 ng/ml nos pacientes com LES. Quando os pacientes foram classificados pelo estado de vitamina D, a seguinte distribuição foi observada: 55 (30,4%) normais (≥30 ng/ml), 63 (34,8%) insuficientes (20-30 ng/ml), 52 (28,7%) deficientes (<20 ng/ml) e 11 (6,1%) com níveis criticamente baixos (<10 ng/ml). Cinquenta e seis por cento dos pacientes com deficiência estavam usando pelo menos 800 UI de vitamina D por dia. Baseada na distribuição genotípica, a concentração da 25(OH)D foi significativamente maior nos pacientes com genótipo f/f, quando comparados com os pacientes com genótipo F/F (31,614,1 ng/ml versus 23,09,2 ng/ml, p=0,004). Níveis de vitamina D não foram associados com aspectos clínicos e laboratoriais do LES. Conclusões: Os polimorfismos BsmI e FokI não apresentaram associação com LES nos nossos pacientes eurodescendentes estudados. O polimorfimo FokI mostrou influência significativa nos níveis da 25(OH)D, o que reforça o papel deste polimorfismo na atividade funcional do VDR. Este achado poderia ser considerado em futuros estudos clínicos e experimentais envolvendo dosagem da vitamina D. A concentração da 25(OH)D necessária para manter o bom funcionamento do sistema musculoesquelético, cardiovascular e imunológico deveria ser individualizada para cada paciente e novas orientações sobre a suplementação de vitamina D poderiam ter que levar em consideração a ancestralidade genética. Assim, estudos adicionais são necessários para estabelecer definições dos níveis ideais de vitamina D geneticamente especificados. / Introduction: Vitamin D has pleiotropic actions on many chronic diseases. The expression of the VDR (vitamin D receptor) in various cells of the immune system strengthens the possible influence of vitamin D on autoimmune diseases. Genetic polymorphisms located in VDR gene may determine changes in the mechanisms of action of vitamin D, but with results still unknown. The BsmI VDR polymorphism was associated with systemic lupus erythematosus (SLE) in Asian patients. Studies with SLE patients in Brazil have not been conducted. Objectives: To investigate the possibility of BsmI and FokI polymorphisms of VDR gene causing increased risk for development of SLE and to evaluate the possible association of these polymorphisms with clinical and laboratory manifestations of the disease. To determine serum levels of 25-hydroxyvitamin D [25(OH)D)] in patients and to investigate the possible association of their concentrations with the studied polymorphisms and clinical and laboratory expressions of SLE. Materials and methods: Case-control study involving 195 SLE patients and 201 healthy controls from the same geographical area. The BsmI and FokI polymorphisms of VDR gene were studied. Serum 25(OH)D levels were measured in the cases. Genotyping was performed by Restriction Fragment Length Polymorphism-Polymerase Chain Reaction (RFLP-PCR), using primers and restriction enzymes specific for each polymorphism. The measurement of 25(OH)D was performed by chemiluminescence. The clinical and laboratory data were collected from medical records. Results: There was no statistically significant difference in genotypic and allelic frequencies of BsmI and FokI polymorphisms among European-derived cases and controls. There was no association between clinical and laboratory features in SLE patients and the studied polymorphisms. The mean serum levels of 25(OH)D were 25.51±11.43 ng/ml in SLE patients. When patients were classified according to vitamin D status, the following distribution was observed: 55 (30.4%) had normal (≥30 ng/ml), 63 (34.8%) insufficient (20-30 ng/ml), 52 (28.7%) deficient (<20 ng/ml) and 11 (6,1%) critically low serum levels (<10 ng/ml). Fifty six percent of patients with deficiency received at least 800 IU of vitamin D per day. Based on genotype distribution, 25(OH)D levels were significantly higher in patients carrying the f/f genotype, when compared to patients carrying the F/F genotype (31.614.1 ng/ml versus 23.09.2 ng/ml, p=0.004). Vitamin D levels were not associated with clinical and laboratory features of SLE. Conclusions: The BsmI and FokI polymorphisms did not present association with SLE in our European-derived studied patients. The FokI polymorphism showed significant influence on 25(OH)D levels, reinforcing its role in functional activity of VDR. This finding may be considered in future clinical and experimental studies involving vitamin D measurements. Serum concentrations of 25(OH)D required to maintain optimal musculoskeletal, cardiovascular and immune health should be individualized for each patient and new guidelines about vitamin D supplementation may have to take into consideration the individual genetic background. Genetic-specific definitions of ideal levels of vitamin D in SLE should therefore be established in future studies.

Introdução: A vitamina D tem ações pleiotrópicas em muitas doenças crônicas. A expressão do receptor da vitamina D (VDR - vitamin D receptor) em diversas células do sistema imune reforça a possível influência da vitamina D nas doenças autoimunes. Polimorfismos genéticos localizados no gene VDR podem determinar alterações nos mecanismos de ação da vitamina D, porém com resultados ainda pouco conhecidos. O polimorfismo BsmI do gene VDR foi associado com lúpus eritematoso sistêmico (LES) em pacientes asiáticos. Estudos com pacientes lúpicos no Brasil ainda não foram realizados. Objetivos: Investigar a possibilidade dos polimorfismos BsmI e FokI do gene VDR aumentarem o risco para o desenvolvimento do LES e avaliar a possível associação destes polimorfismos com manifestações clínicas e laboratoriais da doença. Determinar os níveis séricos da 25-hidroxivitamina D [25(OH)D)] nos pacientes e investigar a possível associação das suas concentrações com os polimorfismos estudados e expressões clínicas e laboratoriais do LES. Materiais e métodos: Estudo caso-controle envolvendo 195 pacientes com LES e 201 controles saudáveis da mesma área geográfica. Foram pesquisados os polimorfismos BsmI e FokI do gene VDR. Os níveis séricos da 25(OH)D foram dosados nos casos. A genotipagem foi realizada por Restriction Fragment Length Polymorphism-Polimerase Chain Reaction (RFLP-PCR), usando primers e enzimas de restrição específicas para cada polimorfismo. A dosagem da 25(OH)D foi realizada por quimioluminescência. Os dados clínicos e laboratoriais foram coletados dos prontuários. Resultados: Não houve diferença estatisticamente significativa nas frequências genotípicas e alélicas dos polimorfismos BsmI e FokI entre casos e controles eurodescendentes. Não houve associação entre as manifestações clínicas e laboratoriais do LES e os polimorfismos estudados. Os níveis séricos médios da 25(OH)D foram de 25,51±11,43 ng/ml nos pacientes com LES. Quando os pacientes foram classificados pelo estado de vitamina D, a seguinte distribuição foi observada: 55 (30,4%) normais (≥30 ng/ml), 63 (34,8%) insuficientes (20-30 ng/ml), 52 (28,7%) deficientes (<20 ng/ml) e 11 (6,1%) com níveis criticamente baixos (<10 ng/ml). Cinquenta e seis por cento dos pacientes com deficiência estavam usando pelo menos 800 UI de vitamina D por dia. Baseada na distribuição genotípica, a concentração da 25(OH)D foi significativamente maior nos pacientes com genótipo f/f, quando comparados com os pacientes com genótipo F/F (31,614,1 ng/ml versus 23,09,2 ng/ml, p=0,004). Níveis de vitamina D não foram associados com aspectos clínicos e laboratoriais do LES. Conclusões: Os polimorfismos BsmI e FokI não apresentaram associação com LES nos nossos pacientes eurodescendentes estudados. O polimorfimo FokI mostrou influência significativa nos níveis da 25(OH)D, o que reforça o papel deste polimorfismo na atividade funcional do VDR. Este achado poderia ser considerado em futuros estudos clínicos e experimentais envolvendo dosagem da vitamina D. A concentração da 25(OH)D necessária para manter o bom funcionamento do sistema musculoesquelético, cardiovascular e imunológico deveria ser individualizada para cada paciente e novas orientações sobre a suplementação de vitamina D poderiam ter que levar em consideração a ancestralidade genética. Assim, estudos adicionais são necessários para estabelecer definições dos níveis ideais de vitamina D geneticamente especificados. / Introduction: Vitamin D has pleiotropic actions on many chronic diseases. The expression of the VDR (vitamin D receptor) in various cells of the immune system strengthens the possible influence of vitamin D on autoimmune diseases. Genetic polymorphisms located in VDR gene may determine changes in the mechanisms of action of vitamin D, but with results still unknown. The BsmI VDR polymorphism was associated with systemic lupus erythematosus (SLE) in Asian patients. Studies with SLE patients in Brazil have not been conducted. Objectives: To investigate the possibility of BsmI and FokI polymorphisms of VDR gene causing increased risk for development of SLE and to evaluate the possible association of these polymorphisms with clinical and laboratory manifestations of the disease. To determine serum levels of 25-hydroxyvitamin D [25(OH)D)] in patients and to investigate the possible association of their concentrations with the studied polymorphisms and clinical and laboratory expressions of SLE. Materials and methods: Case-control study involving 195 SLE patients and 201 healthy controls from the same geographical area. The BsmI and FokI polymorphisms of VDR gene were studied. Serum 25(OH)D levels were measured in the cases. Genotyping was performed by Restriction Fragment Length Polymorphism-Polymerase Chain Reaction (RFLP-PCR), using primers and restriction enzymes specific for each polymorphism. The measurement of 25(OH)D was performed by chemiluminescence. The clinical and laboratory data were collected from medical records. Results: There was no statistically significant difference in genotypic and allelic frequencies of BsmI and FokI polymorphisms among European-derived cases and controls. There was no association between clinical and laboratory features in SLE patients and the studied polymorphisms. The mean serum levels of 25(OH)D were 25.51±11.43 ng/ml in SLE patients. When patients were classified according to vitamin D status, the following distribution was observed: 55 (30.4%) had normal (≥30 ng/ml), 63 (34.8%) insufficient (20-30 ng/ml), 52 (28.7%) deficient (<20 ng/ml) and 11 (6,1%) critically low serum levels (<10 ng/ml). Fifty six percent of patients with deficiency received at least 800 IU of vitamin D per day. Based on genotype distribution, 25(OH)D levels were significantly higher in patients carrying the f/f genotype, when compared to patients carrying the F/F genotype (31.614.1 ng/ml versus 23.09.2 ng/ml, p=0.004). Vitamin D levels were not associated with clinical and laboratory features of SLE. Conclusions: The BsmI and FokI polymorphisms did not present association with SLE in our European-derived studied patients. The FokI polymorphism showed significant influence on 25(OH)D levels, reinforcing its role in functional activity of VDR. This finding may be considered in future clinical and experimental studies involving vitamin D measurements. Serum concentrations of 25(OH)D required to maintain optimal musculoskeletal, cardiovascular and immune health should be individualized for each patient and new guidelines about vitamin D supplementation may have to take into consideration the individual genetic background. Genetic-specific definitions of ideal levels of vitamin D in SLE should therefore be established in future studies.

Estudos de polimorfismos podem auxiliar na detecção de pessoas com maior risco de desenvolver câncer, caracterização de evolução diferenciada e resposta distinta ao tratamento quimioterápico ou radioterápico. O conhecimento de como estão distribuídas as frequências genotípicas é relevante quando se estuda uma população específica. Neste trabalho foi analisado os polimorfismos da enzima metilenotetrahidrofolatoredutase (MTHFR) em pacientes com Câncer Colorretal (CCR). A MTHFR tem papel importante no metabolismo do folato, metilação e síntese do DNA. A metilação do DNA desempenha um papel crítico no controle da atividade gênica. As vias de metilação e variações do gene MTHFR podem afetar o desenvolvimento do câncer e prognósticos de doenças, com isso seus efeitos precisam ser monitorados de perto no tratamento do câncer. Os genótipos variantes dos polimorfismos MTHFR677 C >T e MTHFR1298 A>C do gene da MTHFR estão associados à diminuição importante da atividade desta enzima. Este trabalho teve como objetivo verificar a frequência dos polimorfismos MTFR (677C > T e 1298A > C) em pacientes com adenocarcinomacolorretal e analisar estas frequências com os dados clinicopatológicos, incluindo-se: sexo, idade, localização tumoral, tipo histológico, antecedentes de tabagismo e alcoolismo e sobrevida dos pacientes. Duzentos e vinte cinco pacientes com o diagnóstico de adenocarcinomacolorretal, histologicamente confirmado, admitidos no Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo formam o grupo caso. Utilizou-se a análise do PCR em Tempo Real para determinar os genótipos os polimorfismos através dos ensaios TaqMan ® SNP GenotypingAssay. Os resultados encontrados foram associados aos dados epidemiológicos e clinicopatológicos dos pacientes. As populações estão em equilíbrio de Hardy-Weinberg. Determinaram-se as frequências dos polimorfismos MTFR (677C > T e 1298A > C) em pacientes com adenocarcinomacolorretal onde foram levantadas e agrupadas por genótipos assim como a significância. Na análise das razões de risco de óbito por CCR na presença dos genótipos estudados não foram encontrada associações estatisticamente significativas. A curva de sobrevida comparando os genótipos no teste de Long Rank para os SNPs MTHFR 677C > T e 1298A > C não mostraram diferenças significativas na sobrevida global para pacientes com CCR. Conclui-se que as frequências dos polimorfismos MTFR (677C > T e 1298A > C) em pacientes com adenocarcinoma colorretal foram levantadas e metade dos indivíduos apresentaram frequências genotípicas de homozigotos selvagens nos dois polimorfismos estudados (CC e AA), após as associações dos polimorfismos mencionados com os dados clinicopatológicos, sexo, idade, localização tumoral, tipo histológico, antecedentes de tabagismo e alcoolismo e sobrevida não houve associações estatisticamente significativas / Polymorphism studies may help to detect people at higher risk of developing cancer, characterization of differentiated evolution, distinct response to chemotherapeutic or radiotherapeutic treatment, knowledge of how genotype frequencies are distributed becomes necessary for any work with a specific population. In this work, the polymorphisms of the enzyme methylenetetrahydrofolatoreductase (MTHFR) were analyzed in patients with Colorectal Cancer (CRC). MTHFR plays an important role in folate metabolism, methylation and DNA synthesis. DNA methylation plays a critical role in the control of gene activity. Methylation pathways and variations of the MTHFR gene may affect the development of cancer and prognosis of diseases, so their effects need to be closely monitored in the treatment of cancer. The variant genotypes of the MTHFR677 C > T and MTHFR1298 A > C polymorphisms of the MTHFR gene are associated with a significant decrease in the activity of this enzyme. The aim of this study was to verify the frequency of MTFR polymorphisms (677C > T and 1298A > C) in patients with adenocarcinomes and to analyze these frequencies with clinicopathological data, including: sex, age, tumor location, histological type, history of smoking and alcoholism and patient survival. Two hundred and twenty five patients with the diagnosis of histologically confirmed adenocarcinomes were admitted to the Hospital das Clínicas of the Faculty of Medicine of the University of São Paulo, forming the case group. Real-time PCR analysis was used to determine the genotype polymorphisms through the TaqMan ® SNP Genotyping Assay assays. The results were associated with the epidemiological and clinicopathological data of the patients. The populations are in Hardy-Weinberg equilibrium. The frequencies of the MTFR polymorphisms (677C > T and 1298A > C) were determined in patients with adenocarcinoma-choroid where they were raised and grouped by genotypes as well as significance. The analysis of death risk ratios by RCC in the presence of the studied genotypes, there was no statistically significant associations were found. The survival curve comparing the genotypes in the Long Rank test for MTHFR 677C > T and 1298A > C SNPs did not show significant differences in overall survival for CRC patients. It was concluded that the frequencies of MTFR polymorphisms (677C > T and 1298A > C) in patients with colorectal adenocarcinoma were raised and half of the individuals presented genotype frequencies of wild homozygotes in the two polymorphisms studied (CC and AA), after associations of polymorphisms mentioned, there was no statistically significant association between these polymorphisms and the variables studied: sex, age, tumor location, histological type, history of smoking and alcoholism and survival

Introdução: A vitamina D tem ações pleiotrópicas em muitas doenças crônicas. A expressão do receptor da vitamina D (VDR - vitamin D receptor) em diversas células do sistema imune reforça a possível influência da vitamina D nas doenças autoimunes. Polimorfismos genéticos localizados no gene VDR podem determinar alterações nos mecanismos de ação da vitamina D, porém com resultados ainda pouco conhecidos. O polimorfismo BsmI do gene VDR foi associado com lúpus eritematoso sistêmico (LES) em pacientes asiáticos. Estudos com pacientes lúpicos no Brasil ainda não foram realizados. Objetivos: Investigar a possibilidade dos polimorfismos BsmI e FokI do gene VDR aumentarem o risco para o desenvolvimento do LES e avaliar a possível associação destes polimorfismos com manifestações clínicas e laboratoriais da doença. Determinar os níveis séricos da 25-hidroxivitamina D [25(OH)D)] nos pacientes e investigar a possível associação das suas concentrações com os polimorfismos estudados e expressões clínicas e laboratoriais do LES. Materiais e métodos: Estudo caso-controle envolvendo 195 pacientes com LES e 201 controles saudáveis da mesma área geográfica. Foram pesquisados os polimorfismos BsmI e FokI do gene VDR. Os níveis séricos da 25(OH)D foram dosados nos casos. A genotipagem foi realizada por Restriction Fragment Length Polymorphism-Polimerase Chain Reaction (RFLP-PCR), usando primers e enzimas de restrição específicas para cada polimorfismo. A dosagem da 25(OH)D foi realizada por quimioluminescência. Os dados clínicos e laboratoriais foram coletados dos prontuários. Resultados: Não houve diferença estatisticamente significativa nas frequências genotípicas e alélicas dos polimorfismos BsmI e FokI entre casos e controles eurodescendentes. Não houve associação entre as manifestações clínicas e laboratoriais do LES e os polimorfismos estudados. Os níveis séricos médios da 25(OH)D foram de 25,51±11,43 ng/ml nos pacientes com LES. Quando os pacientes foram classificados pelo estado de vitamina D, a seguinte distribuição foi observada: 55 (30,4%) normais (≥30 ng/ml), 63 (34,8%) insuficientes (20-30 ng/ml), 52 (28,7%) deficientes (<20 ng/ml) e 11 (6,1%) com níveis criticamente baixos (<10 ng/ml). Cinquenta e seis por cento dos pacientes com deficiência estavam usando pelo menos 800 UI de vitamina D por dia. Baseada na distribuição genotípica, a concentração da 25(OH)D foi significativamente maior nos pacientes com genótipo f/f, quando comparados com os pacientes com genótipo F/F (31,614,1 ng/ml versus 23,09,2 ng/ml, p=0,004). Níveis de vitamina D não foram associados com aspectos clínicos e laboratoriais do LES. Conclusões: Os polimorfismos BsmI e FokI não apresentaram associação com LES nos nossos pacientes eurodescendentes estudados. O polimorfimo FokI mostrou influência significativa nos níveis da 25(OH)D, o que reforça o papel deste polimorfismo na atividade funcional do VDR. Este achado poderia ser considerado em futuros estudos clínicos e experimentais envolvendo dosagem da vitamina D. A concentração da 25(OH)D necessária para manter o bom funcionamento do sistema musculoesquelético, cardiovascular e imunológico deveria ser individualizada para cada paciente e novas orientações sobre a suplementação de vitamina D poderiam ter que levar em consideração a ancestralidade genética. Assim, estudos adicionais são necessários para estabelecer definições dos níveis ideais de vitamina D geneticamente especificados. / Introduction: Vitamin D has pleiotropic actions on many chronic diseases. The expression of the VDR (vitamin D receptor) in various cells of the immune system strengthens the possible influence of vitamin D on autoimmune diseases. Genetic polymorphisms located in VDR gene may determine changes in the mechanisms of action of vitamin D, but with results still unknown. The BsmI VDR polymorphism was associated with systemic lupus erythematosus (SLE) in Asian patients. Studies with SLE patients in Brazil have not been conducted. Objectives: To investigate the possibility of BsmI and FokI polymorphisms of VDR gene causing increased risk for development of SLE and to evaluate the possible association of these polymorphisms with clinical and laboratory manifestations of the disease. To determine serum levels of 25-hydroxyvitamin D [25(OH)D)] in patients and to investigate the possible association of their concentrations with the studied polymorphisms and clinical and laboratory expressions of SLE. Materials and methods: Case-control study involving 195 SLE patients and 201 healthy controls from the same geographical area. The BsmI and FokI polymorphisms of VDR gene were studied. Serum 25(OH)D levels were measured in the cases. Genotyping was performed by Restriction Fragment Length Polymorphism-Polymerase Chain Reaction (RFLP-PCR), using primers and restriction enzymes specific for each polymorphism. The measurement of 25(OH)D was performed by chemiluminescence. The clinical and laboratory data were collected from medical records. Results: There was no statistically significant difference in genotypic and allelic frequencies of BsmI and FokI polymorphisms among European-derived cases and controls. There was no association between clinical and laboratory features in SLE patients and the studied polymorphisms. The mean serum levels of 25(OH)D were 25.51±11.43 ng/ml in SLE patients. When patients were classified according to vitamin D status, the following distribution was observed: 55 (30.4%) had normal (≥30 ng/ml), 63 (34.8%) insufficient (20-30 ng/ml), 52 (28.7%) deficient (<20 ng/ml) and 11 (6,1%) critically low serum levels (<10 ng/ml). Fifty six percent of patients with deficiency received at least 800 IU of vitamin D per day. Based on genotype distribution, 25(OH)D levels were significantly higher in patients carrying the f/f genotype, when compared to patients carrying the F/F genotype (31.614.1 ng/ml versus 23.09.2 ng/ml, p=0.004). Vitamin D levels were not associated with clinical and laboratory features of SLE. Conclusions: The BsmI and FokI polymorphisms did not present association with SLE in our European-derived studied patients. The FokI polymorphism showed significant influence on 25(OH)D levels, reinforcing its role in functional activity of VDR. This finding may be considered in future clinical and experimental studies involving vitamin D measurements. Serum concentrations of 25(OH)D required to maintain optimal musculoskeletal, cardiovascular and immune health should be individualized for each patient and new guidelines about vitamin D supplementation may have to take into consideration the individual genetic background. Genetic-specific definitions of ideal levels of vitamin D in SLE should therefore be established in future studies.

La sélection génomique substitue à la connaissance de la généalogie celle des séquences d’ADN et connait un succès spectaculaire dans la sélection des bovins laitiers. En équin, le gain de précision pour les valeurs génétiques en CSO a été estimé faible entre la généalogie et la génomique, éventuellement à cause des particularités des populations d’apprentissage et de validation. L’objectif est de définir pour les races équines les conditions d’efficacité et de fonctionnement de la sélection génomique. La partie théorique de la thèse a consisté en une méta-analyse afin de comprendre le lien entre précision théorique et observée en fonction des paramètres des populations. L’étude a montré l’importance du nombre efficace de marqueurs Me. Ce paramètre spécifique de la population, de la structure génomique et de la parenté doit être évalué, au même titre que l’héritabilité en génétique classique. D’un point de vue pratique, la 1ère voie d’amélioration était de rechercher des gènes à effet majeur sur l’aptitude au concours de saut d’obstacles (CSO) ou au concours complet. Aucun gène majeur n’a été localisé malgré des détections significatives. Le 2nd levier pour améliorer l’estimation des valeurs génétiques en CSO était d’utiliser le Single-Step, méthode qui combine l’information génomique des étalons génotypés et la généalogie de l’ensemble des chevaux non génotypés utilisés pour l’indexation. L’évaluation pour le CSO a donc été revisitée. Malgré le re-calcul de l’héritabilité et l’application des points sur toute la période, le gain en précision reste faible. La sélection génomique a également été testée sur des chevaux d’endurance, mais comme pour le CSO les précisions obtenues pour le moment ne sont pas assez élevées pour justifier une utilisation de la sélection génomique. Récemment, un gène majeur agissant sur l’aptitude à trotter (DMRT3) a été identifié. Malgré l’effet très négatif d’un allèle sur la qualification et les performances précoces, le Trotteur français (TF) est polymorphe pour le gène à cause d’un effet positif de ce même allèle sur les performances tardives. La sélection classique et la sélection génomique ont été comparées en incluant ou non dans le modèle un marqueur lié à DMRT3, nous permettant d’identifier la meilleure combinaison de modèle et de méthode à utiliser pour estimer les valeurs génétiques du TF. Enfin, le paramètre Me a été estimé dans les populations de chevaux utilisées au cours de la thèse, et les résultats des évaluations génomiques ont été comparés en fonction de Me et des autres paramètres influant sur la précision de la sélection génomique. Deux nouveaux projets prévoyant de génotyper des chevaux de CSO d’une part et des TF d’autre part devraient permettre respectivement d’améliorer la précision de l’évaluation génomique en CSO et de confirmer l’intérêt de la prise en compte de DMRT3 dans l’évaluation génomique des TF. / Genomic selection uses genotypes information instead of pedigree information for the estimation of breeding values. In dairy cattle, the selection schemes were greatly improved with this method. In horses, a first attempt of genomic selection showed that the evaluation accuracy was not much improved when using genotypes information compared to classic evaluation, possibly because of the structure of the reference and validation populations. The objective of the thesis was to define the theoretical and practical conditions for the use of genomic selection in horses. The theoretical work of the thesis consisted in a meta-analysis to understand the relation between observed and theoretical accuracy depending on the parameters of the population. We proved the importance of the effective number of independent segments in the genome Me. This parameter is specific of the population and of the genomic structure and relationship structure. We recommend to estimate this parameter before genomic evaluation, just like heritability that is estimated before genetic evaluation. Regarding practical tasks of the thesis, the first solution to improve the breeding values estimation for jumping performances was to look for genes having a major effect on performances in jumping competitions and three-day’s events, but no major gene was evidence in spite of significant detections. The 2nd solution was to perform a single-step evaluation. This method combines information from genotyped stallions and from the pedigree of the whole population. Even if the heritability was re-estimated and points distributed to all horses to have a homogeneous criteria, the accuracy of genomic evaluation was not much improved. Genomic selection was also tested on horses running endurance races, but as for jumping the accuracy was not high enough. Recently, a major gene having a huge effect on the ability of horses to trot was evidenced (DMRT3). Even if one allele has a negative effect on qualification and early earnings, French Trotter (FT) is still heterozygote because of a positive effect of this allele on late performances. Genetic and genomic evaluations were compared with or without using in the model a SNP linked to DMRT3 as a fixed effect. This study allowed identifying the best combination of model and method to use for estimation of FT breeding values. Finally, the parameter Me was estimated in the populations of horses used in the thesis. The results of genomic evaluations were compared according to Me and the other parameters having an influence on the accuracy of genomic evaluations. Two new projects will genotype more jumping horses and FT, they should allow to improve the accuracy of genomic evaluation for jumping horses and to acknowledge the interest of using DMRT3 in the genomic evaluation of FT.

No description available.

Not much is known about the mechanisms affecting the genetic composition of populations of different species. To investi­gate one of these potential mechanisms, mating behaviour, the fruit fly Drosophila melanogaster, was chosen as an experimen­tal animal. To quantify mating behaviour in easily measurable parameters, it was subdivided into several distinct components; mating activity, mating time, mating competition ability and male mating capacity. As behavioural components to a great extent are influenced by environmental conditions all experiments were performed under controlled temperature and humidity. All components of mating behaviour were estimated by introducing females and males into mating chambers. Mating behaviour seems to be one of the major factors affect­ing the genetic composition of Drosophila melanogaster popula­tions. The experiments performed showed that differences in mating properties led to a substantial sexual selection among the genotypes. This selection was of a stabilizing type with regard to characters associated to bristle number and Y chromo­somal chromatin. This selection situation seems to warrant the retention of intermediate phenotypes in a population and will therefore contribute to the genetic variation present. Differences in mating properties were also shown to be able to maintain a balanced polymorphism for allozyme variants in populations. This maintenance was obtained through different forms of balancing selection as heterozygous superiority in sexual activity and balancing selection between female and male genotypes. Heterozygous superiority or overdominance in fitness always leads to balanced polymorphism through segre­gation of individuals with lowered fitness. The balancing selection between the female and male genotypes is best looked upon as a form of marginal overdominance, conferring the aver­aged highest fitness to the heterozygous genotype, thereby maintaining the polymorphism of the population. / <p>Härtill 5 uppsatser</p> / digitalisering@umu

Master of Science / Department of Animal Sciences and Industry / Twig T. Marston / One hundred ninety-three crossbred steers from two herds were used to determine the association of leptin gene polymorphisms and effects of feedlot management of lean and fat steers on carcass performance. Steers were sorted into FAT and LEAN groups by ultrasound backfat at weaning and randomly assigned to a finishing phase. Steers were assigned to a backgrounding phase (BACK) and were fed a forage-based diet for 90 days or directly entered a feedlot phase (FEED). Genotypes were determined by IGENITY® (Atlanta, GA) for a panel of nine single nucleotide polymorphisms (SNP) in the leptin gene (UASMS1, UASMS2, C963T, E2FB, A1457G, and A252T), leptin receptor (T945M), growth hormone receptor (G200A), and fat metabolism enzyme (K232A). Initial backfat (BF) means for the FAT and LEAN group were 3.4 mm and 1.8 mm, respectively. Mean on-test weight was heavier for FAT (306.5 kg) than LEAN (292.9 kg). Age-adjusted hot carcass weights (HCWT) were heavier for LEAN/BACK when compared to FAT/FEED and FAT/BACK (P<0.05). Dressing percent for the FAT/FEED group tended to be higher (P<0.10) over all groups except LEAN/BACK. Steers that went directly to the feedlot had higher marbling scores than backgrounded groups. FAT/FEED had higher 12th rib BF than the other contemporaries. None of the SNPs were useful for predicting ultrasound BF at weaning. Some association was detected with UASMS2 and HCWT (P<0.10) resulting in an 11 kg difference between genotype CC and CT (P<0.05). Five of the leptin polymorphisms (UASMS1, UASMS2, A1457G, C963T, and E2FB) were associated with adjusted carcass BF (P=0.01, 0.06, 0.01, 0.01, and 0.01, respectively) and calculated yield grade (P<0.01). A252T was associated with REA, and genotype TT was larger than AA and AT (P<0.05). This study suggests that segregation by initial fatness estimates and feedlot management strategies has the opportunity to increase HCWT by 35 kg. Sorting cattle upon feedlot entry by ultrasound BF and segregation using genetic markers are useful tools that can assist in the estimation of carcass composition in the live animal. With additional research, the possibility exists to incorporate genetic markers into feedlot selection to assist in marketing decisions.

BACKGROUND:General, breed- and diet-dependent associations between feed efficiency in beef cattle and single nucleotide polymorphisms (SNPs) or haplotypes were identified on a population of 1321 steers using a 50K SNP panel. Genomic associations with traditional two-step indicators of feed efficiency - residual feed intake (RFI), residual average daily gain (RADG), and residual intake gain (RIG) - were compared to associations with two complementary one-step indicators of feed efficiency: efficiency of intake (EI) and efficiency of gain (EG). Associations uncovered in a training data set were evaluated on independent validation data set. A multi-SNP model was developed to predict feed efficiency. Functional analysis of genes harboring SNPs significantly associated with feed efficiency and network visualization aided in the interpretation of the results.RESULTS:For the five feed efficiency indicators, the numbers of general, breed-dependent, and diet-dependent associations with SNPs (P-value<0.0001) were 31, 40, and 25, and with haplotypes were six, ten, and nine, respectively. Of these, 20 SNP and six haplotype associations overlapped between RFI and EI, and five SNP and one haplotype associations overlapped between RADG and EG. This result confirms the complementary value of the one and two-step indicators. The multi-SNP models included 89 SNPs and offered a precise prediction of the five feed efficiency indicators. The associations of 17 SNPs and 7 haplotypes with feed efficiency were confirmed on the validation data set. Nine clusters of Gene Ontology and KEGG pathway categories (mean P-value<0.001) including, 9nucleotide binding / ion transport, phosphorous metabolic process, and the MAPK signaling pathway were overrepresented among the genes harboring the SNPs associated with feed efficiency.CONCLUSIONS:The general SNP associations suggest that a single panel of genomic variants can be used regardless of breed and diet. The breed- and diet-dependent associations between SNPs and feed efficiency suggest that further refinement of variant panels require the consideration of the breed and management practices. The unique genomic variants associated with the one- and two-step indicators suggest that both types of indicators offer complementary description of feed efficiency that can be exploited for genome-enabled selection purposes.

Thesis (MSc)--Stellenbosch University, 2012. / ENGLISH ABSTRACT: This study aimed to combine the principles of crystal engineering with the properties of cyclotriphosphazene derivatives to construct supramolecular assemblies in the solid state. The ease with which the chloro substituents on cyclotriphosphazenes can be replaced makes them ideal candidates for this study. The substituents were chosen for their ability to form either hydrogen bonding interactions or halogen bonding interactions in the solid state. The cyclotriphosphazene derivatives were co-crystallised with various small organic molecules with complementary functional groups, as well as with other cyclophosphazene derivatives. The aim was to form co-crystals or solvates with these cyclophosphazene derivatives as co-crystals contain a wealth of information regarding the forces governing the aggregation of molecules in the solid state. Cyclotriphosphazenes, with their array of substituents, could broaden the range of potential interactions governing crystalline assembly. Fifteen cyclotriphosphazene derivatives were synthesised and characterised in this study. The novel crystal structures of two cyclotriphosphazene derivatives have been elucidated by single crystal X-ray diffraction. These are 2,2-bis(4-formylphenoxy)-4,4,6,6-bis[spiro(2',2"-dioxy-1',1"-biphenylyl)]cyclotriphosphazene and hexakis(4-cyano-phenoxy)cyclotriphosphazene. In the course of this study two novel polymorphs of hexakis(4-fluorophenoxy)cyclotri-phosphazene were identified and studied. The novel triclinic form undergoes an irreversible transformation to the previously reported monoclinic phase at high temperatures. The reported monoclinic phase, however, transforms to a monoclinic C phase in a single-crystal to single-crystal fashion. It is also suspected that this phase transformation is in fact reversible on cooling of the crystal to temperatures below -45 °C. One novel co-crystal structure of hexakis(4-pyridyloxy)cyclotriphosphazene with terephthalic acid was identified and characterised. However, analysis of the Cambridge Structural Database indicates that co-crystal formation with cyclophosphazenes is not a commonly occurring phenomenon. This leads to the conclusion that cyclotriphosphazenes can be used in crystal engineering as supramolecular building blocks, but their shape and size tend to inhibit the formation of co-crystals. Therefore co-crystal formers have to be chosen with great care. / AFRIKAANSE OPSOMMING: Die doel van hierdie studie was om die beginsels van kristalingenieurswese te kombineer met die eienskappe van siklotrifosfaseen afgeleides om sodoende supramolekulêre versamelings in die vastetoestand te bou. Die gemak waarmee die chloor substituente op die siklotrifosfaseenring vervang kan word, maak hierdie molekules ideaal vir hierdie studie. Die substituente is gekies op grond van hul potensiaal om waterstofbindings of intermolekulêre halogeenbindings in die vastetoestand te vorm. Ko-kristallisasie eksperimente is met die siklotrifosfaseen afgeleides en verskeie klein organiese molekules met komplementêre funksionele groepe uitgevoer, asook tussen die verskeie siklotrifosfaseen afgeleides met mekaar. Die doel was om mede-kristalle of solvate met hierdie siklotrifosfaseen afgeleides te vorm aangesien mede-kristalle ‘n magdom inligting bevat rakende die kragte wat die versameling van molekules in die vaste fase beheer. Die siklotrifosfaseen afgeleides wat ‘n wye verskeidenheid substituente kan dra, kan hierdeur die moontlike intermolekulêre interaksies wat die versameling in die kristallyne vaste fase beheer verbreed. In hierdie studie is vyftien siklotrifosfaseen afgeleides gesintetiseer en gekarakteriseer. Die voorheen onbekende kristalstrukture van twee siklotrifosfaseen afgeleides is in hierdie studie geïdentifiseer, naamlik 2,2-bis(4-formielfenoksie)-4,4,6,6-bis[spiro(2',2"-dioksie-1',1"-bifeniliel)]siklotrifosfaseen en heksa(4-sianofenoksie)siklotrifosfaseen. Die strukture is bepaal deur enkelkristal X-straaldiffraksie. In die loop van hierdie studie is twee voorheen onbekende polimorfs van heksa(4-fluorofenoksie)siklotrifosfaseen geïdentifiseer en bestudeer. Die nuwe trikliniese vorm ondergaan ‘n onomkeerbare faseverandering na die monokliniese vorm by hoë temperature. Die bekende monokliniese P fase ondergaan egter ‘n verdere faseverandering na ‘n monokliniese C fase. Hierdie geskied as ‘n enkel-kristal na ‘n enkel-kristal faseverandering. Daar word ook gespekuleer dat hierdie spesifieke faseverandering wel omkeerbaar is indien die kristal na -45 °C afgekoel word. Een nuwe mede-kristal tussen heksa(4-pyridieloksie)sikotrifosfaseen en 1,3-dibensoësuur is in hierdie studie geïdentifiseer en gekarakteriseer. ‘n Analise van die Cambridge Strukturele Databasis het egter aangedui dat die vorming van mede-kristalle nie ‘n alledaagse verskynsel is in sikotrifosfaseen afgeleides nie. Dit lei tot die gevolgtrekking dat sikotrifosfaseen molekules wel in kristalingenieurswese gebruik kan word as supramolekulêre boustene, maar dat die vorm en grootte van die molekules die kristallisering van mede-kristalle verhoed. Dus moet die molekules wat saam met die siklotrifosfaseen molekules gekristalliseer wil word, goed deurdink word.