Os objetivos deste estudo foram: estimar parâmetros genéticos para: coloração da conjuntiva ocular (CCO), contagem de ovos por grama de fezes (OPG), volume globular (VG), proteína plasmática total (PPT), escore da condição corporal (ECC) e peso corporal (PC) e, ainda, explorar o perfil genético da população, utilizando análises de agrupamento com base nos valores genéticos. E estimar parâmetros genéticos para peso corporal (PC) e características de conformação (perímetro torácico (PT), altura da garupa (AG), altura da cernelha (AC), largura da garupa (LG), comprimento corporal (CC) e escore de condição corporal (ECC)) com intuito de definir critérios de seleção. Foram analisadas um total de 2.525 informações de 771 animais nascidos entre 2002 e 2013, filhos de 68 carneiros e 352 ovelhas, pertencentes a sete rebanhos localizados no estado de São Paulo. Os animais foram avaliados mensalmente durante junho de 2013 a outubro de 2014. Os componentes de covariância foram estimados por modelo animal em análises multicaracterísticas, por meio de abordagem Bayesiana. As estimativas de herdabilidade para CCO, PC, VG, PPT, OPG e ECC foram 0,21 (0,04); 0,18 (0,05); 0,30 (0,06); 0,17 (0,05); 0,19 (0,03) e 0,31 (0,07), respectivamente, indicando que a seleção pode ser realizada com base no valor genético dos indivíduos para estas características. As correlações genéticas entre a CCO e PC, VG, PPT, OPG e ECC foram -0,40 (0,17); -0,63 (0,09); -0,23 (0,15); 0,77 (0,09); -0,59 (0,11), respectivamente, e entre PC e ECC a correlação genética foi de 0,84 (0,15). Assim como as outras medidas de resistência a verminose, a CCO pode ser incluída como critério na seleção; esta apresenta estimativa de herdabilidade mediana correlação genética favorável com as outras medidas de resistência a verminose e com PC e ECC, além de ser de fácil obtenção e baixo custo. Foi possível obter grupos de indivíduos com perfil genético de resistência/resiliência a verminose a partir das análises de agrupamento. As estimativas de herdabilidade para PC, PT, AG, AC, LG e ECC foram: 0,25 (0,08); 0,22 (0,07); 0,24 (0,07); 0,25 (0,07); 0,19 (0,05) e 0,32 (0,07), respectivamente e as correlações genéticas entre o peso e as medidas corporais foram de alta magnitude, variando entre 0,66 (0,11) a 0,98 (0,016), indicando que as medidas corporais, principalmente o perímetro torácico, pode ser incluído como um critério de seleção complementar ao peso corporal. / The objective of this study was to estimate genetic parameters for conjunctival staining score (CSS), fecal eggs count (FEC), packed cell volume (PCV), total plasma protein (TPP), body condition score (BCS) and body weight (BW), and also explore the genetic profile of the population, using cluster analysis based on genetic values. And to estimate genetic parameters for body weight (BW) and conformation traits (heart girth (HG), hip height (HH), wither height (WH), rump width (RW), body length (BL) and body condition score (BCS)) to define selection criteria. A total of 2,525 records from 771 animals born between 2002 and 2013 to 68 rams and 352 ewes, belonging to five herds located in the São Paulo state were used. The animals were evaluated monthly during June 2013 to October 2014. The covariance components were estimated by animal model multi-trait using Bayesian analysis. The estimates of heritability for CSS, BW, PCV, FEC, BCS and PPT were 0.21 (0.04); 0.18 (0.05); 0.30 (0.06); 0.19 (0.03), 0.31 (0.07) and 0.17 (0.07), respectively, indicating that you can select animals based on the genetic value of individuals. The genetic correlations between CSS and BW, CSS and PCV, CSS and PPT, CCS and FEC, CSS and BCS and between the BW and BCS -0.40 (0.17); -0.63 (0.09); -0.23 (0.15); 0.77 (0.09); 0.84 (0.15), respectively. As other resistance traits the worms, the CCO can be included as a criterion in the selection. For this trait has estimated median heritability (0.21±0.04) and positive genetic correlation with other resistance measures to worms and BW and BCS, as well as being easy to obtain and low cost. It was possible to obtain groups of individuals with genetic profile of resistance / resilience to worms from the cluster analysis. The estimates of heritability for BW, HG, HH, WH, RW, BL and BCS were 0.25 (0.08); 0.22 (0.07); 0.24 (0.07); 0.25 (0.07); 0.19 (0.05) and 0.32 (0.07), respectively and genetic correlations between weight and body measures were highest magnitude, ranging from 0.66 (0.11) to 0.98 (0,016) indicating that body measurements, mainly heart girth, can be included as a criterion in the selection in addition to body weight.

Submitted by (ana.araujo@ufrpe.br) on 2017-02-06T15:24:21Z No. of bitstreams: 1 Andreza Santos da Costa.pdf: 1940240 bytes, checksum: b2083728750a497a89ff9e877813ffd0 (MD5) / Made available in DSpace on 2017-02-06T15:24:21Z (GMT). No. of bitstreams: 1 Andreza Santos da Costa.pdf: 1940240 bytes, checksum: b2083728750a497a89ff9e877813ffd0 (MD5) Previous issue date: 2005-02-07 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / The genotypes of the Heliconia Germoplasm Collection of University Federal Rural of Pernambuco (UFRPE), implanted in December of 2003 in Camaragibe, were valued agronomic traits. In the first stage, information on number of shoots per clump (NPT) and the clump basal area (AOT) of 26 Heliconia spp. genotypes, cultivated at full sun and partial shade, according to the genotype requirements were evaluated. The experimental design was in randomized blocks, with four replications. The NPT was evaluated every 29 days starting 59 days after planting (DAP). The AOT was measured every three months. The NPT 373 DAP varied from 113.2 (H. psittacorum cv. Red Opol) to 37.0 (H. psittacorum cv. Red Gold) grown at full sun, and from 71.0 (H. psittacorum cv. Golden Torch) to 18.3 (H. bihai cv. Nappi Yellow) grown at partial shade condition. At full sun, H. psittacorum cv. Red Opol emitted the greatest number of shoots, occupying only half of the plot area (11.387 cm2). Heliconia x nickeriensis, showed intermediary shoot emission (74,0) and occupied 22.541 cm2. The genotype H. latispatha cv. Yellow Gyro presented the lower AOT (725 cm2) after 304 DAP, in full sun area. At the shaded area, The AOT, varied from 750 cm2 (H. bihai cv. Nappi Yellow) to 10.201 cm2 (H. stricta cv. Fire Bird). Despite the fact that these traits were evaluatedonly during the first 373 days after planting, it was observed that only one plant spacing for heliconia can cause management problems. At second stage were evaluated genetics parameters of seven genotypes of H. psittacorum. The variabilites of the traits was observed: days harvest the inflorescence after shoot formation (DEI); days before harvesting the inflorescence after inflorescence emission (DCI); flower mass stem (MH); number of leaves in the stem at the moment of inflorescence emission (NFI); stem length (CH); and inflorescence length (CI). The higher values of heritability and genetic variation coeficient were 90.49%, 88.85% and 85.48% for DEI, CI and CH, respectively. For genetic coefficients the higher values were 25.46%, 20.78% and 17.8% for DEI, MH and CI, respectively. These results indicate a higher possibility of success to achieve better quality of flower stems by the selection of these traits. The genetic correlation between DEI and DCI (0,75**) indicated that the cultivars with a larger interval betweenthe shoot emission and flower emission also had larger interval between the flower emission and its harvest. Because of the high correlation between these traits and the low heritability for DCI, DEI it is better indicated to base the selection, yielding advantages by indirect selection. The traits MH and NFI presented heritability of 75.20% and 67.77%, and genetic coefficients of 20.78% and 10.09%, respectively. Only the genotype cv. Suriname Sassy presented the lowest MFS and LS, desired aspects in heliconias. The genetic and phenotypic correlation of DEI with NFI was of 0.86** and 0.76** respectively, which may indicate the NL as a marker for flowering. The trait CH demonstrated genetic correlation with DEI and DCI (-0.85** e –0.97**, respectively), which indicates less days from harvest in genotypes with higher length of the stem. / Os genótipos da Coleção de Germoplasma de Helicônias da Universidade Federal Rural de Pernambuco (UFRPE), implantada em dezembro de 2003 no município de Camaragibe, foram avaliados quanto a características genéticas e agronômicas. Na primeira etapa foram avaliados o número de perfilhos por touceira (NPT) e a área de ocupação da touceira (AOT) de 26 genótipos de Heliconia spp., cultivados a pleno sol e a meia sombra, conforme a exigência dos mesmos. O delineamento experimental foi de blocos ao acaso, com quatro repetições. O NPT foi avaliado a cada 29 dias, a partir dos 59 dias após o plantio (DAP). A AOT foi medida a cada três meses. Aos 373 DAP, na área a pleno sol, os genótipos apresentaram uma variação de 37,0 (H. psittacorum cv. Red Gold) a 113,2 perfilhos (H. psittacorum cv. Red Opol), e de 18,3 (H. bihai cv. Nappi Yellow) a 71,0 perfilhos (H. psittacorum cv. Golden Torch), a meia sombra. A H. psittacorum cv. Red Opol, a pleno sol, emitiu mais perfilhos, porém ocupou apenas metade da área da parcela (11.387 cm2), enquanto a Heliconia x nickeriensis, com NPT de 74,0, ocupou 22.541 cm2. Aos 304 DAP, na área a pleno sol, o genótipo que apresentou menor AOT foi H. latispatha cv. Yellow Gyro (725 cm2). A meia sombra a AOT variou de 750 cm2 (H. bihai cv. Nappi Yellow) a 10.201 cm2 (H. stricta cv. Fire Bird). Embora estes caracteres tenham sido avaliados nos primeiros 373 DAP, observou-se que a adoção de um único espaçamento para helicônia acarretará futuros problemas de manejo. Na segunda etapa, foram avaliados parâmetros genéticos em sete genótipos de H. psittacorum, sendo observada variabilidade para os caracteres: dias para emissão da inflorescência a partir da formação do perfilho (DEI); dias para colheita da inflorescência, a partir da sua emissão (DCI); massa da haste floral (MH); número de folhas presentes no pseudocaule no momento da emissão da inflorescência (NFI); comprimento da haste (CH); e comprimento da inflorescência (CI). As maiores herdabilidades e coeficientes de variação genética foram, respectivamente, 97,33%; 85,05%, 84,98%, 84,48 e 82,25%, para DEI, CH, CI, NI e MH, e 27,96%; 23,02% e 16,89%, para DCI, MH e CI. Isto indica maior possibilidade de sucesso com a seleção desses caracteres para o aumento da qualidade das hastes florais através do melhoramento genético. A correlação genética de DEI com NFI foi de 0,52*, o que pode indicar o NFI como marcador para florescimento. O caráter CH apresentou correlações genotípicas com DEI e DCI (-0,72** e -0,81*, respectivamente), indicando que ciclos mais curtos foram observados em genótipos com maior o comprimento da haste. Durante o período de avaliação,, foi registrado o número de flores por touceira dos genótipos. O cv. Golden Torch destacou-se por ter apresentado a maior produção de inflorescências e menor ciclo e o cv. Alan Carle menor produção e o maior ciclo.

Informações de milhares de marcadores genéticos têm sido incluídas nos programas de melhoramento genético, permitindo a seleção dos animais considerando estas informações e a identificações de regiões genômicas associadas às características de interesse econômico. Devido ao alto custo associado a esta tecnologia e às coletas de dados, os dados simulados apresentam grande importância para que novas metodologias sejam estudadas. O objetivo deste trabalho foi avaliar a eficiência do método ssGBLUP utilizando pesos para os marcadores genéticos, informações de genótipo e fenótipos, com ou sem as informações de pedigree, para seleção e associação genômica ampla, considerando diferentes coeficientes de herdabilidade, presença de efeito poligênico, diferentes números de QTL (quantitative trait loci) e pressões de seleção. Adicionalmente, dados de qualidade da carne de ovinos da raça Santa Inês foram comparados com a os padrões descritos para esta raça. A população estudada foi obtida por simulação de dados, e foi composta por 8.150 animais, sendo 5.850 animais genotipados. Os dados simulados foram analisados utilizando o método ssGBLUP com matrizes de relacionamento com ou sem informações de pedigree, utilizando pesos para os marcadores genéticos obtidos em cada iteração. As características de qualidade da carne estudadas foram: área de olho de lombo, espessura de gordura subcutânea, cor, pH ao abate e após 24 horas de resfriamento das carcaças, perdas por cocção e força de cisalhamento. Quanto maior o coeficiente de herdabilidade, melhores foram os resultados de seleção e associação genômica. Para a identificação de regiões associadas a características de interesse, não houve influência do tipo de matriz de relacionamento utilizada. Para as características com e sem efeito poligênico, quando considerado o mesmo coeficiente de herdabilidade, não houve diferenças para seleção genômica, mas a identificação de QTL foi melhor nas características sem efeito poligênico. Quanto maior a pressão de seleção, mais acuradas foram as predições dos valores genéticos genômicos. Os dados de qualidade da carne obtidos de ovinos da raça Santa Inês estão dentro dos padrões descritos para esta raça e foram identificas diversas regiões genômicas associadas às características estudadas. / Thousands of genetic markers data have been included in animal breeding programs to allow the selection of animals considering this information and to identify genomic regions associated to traits of economic interest. Simulated data have great importance to the study of new methodologies due to the high cost associated with this technology and data collection. The objectives of this study were to evaluate the efficiency of the ssGBLUP method using genotype and phenotype information, with or without pedigree information, and attributing weights for genetic markers, for selection and genome-wide association considering different coefficients of heritability, the presence of polygenic effect, different numbers of quantitative trait loci and selection pressures. Additionally, meat quality data of Santa Ines sheep breed were compared with the standards for the breed. The population of simulated data was composed by 8.150 individuals and 5.850 genotyped animals. The simulated data was analysed by the ssGBLUP method and by two relationship matrix, with or without pedigree information, and weights for genetic markers were obtained in every iteration. The traits of meat quality evaluated were: rib eye area, fat thickness, color, pH at slaughter and 24 hours after the carcass cooling, cooking losses and shear force. The results of selection and genomic association were better for the traits with the highest heritability coefficients. For traits with the greater selection pressure, more accurate predictions of the genomic breeding values were obtained. There was no difference between the relationship matrix studied to identify the regions associated with traits of interest. For the traits with and without polygenic effect, considering the same heritability coefficient, they did not show differences in genomic selection, but the identification of the QTL was better for traits without polygenic effect. The meat quality data obtained from Santa Ines sheep breed are in accordance with the standards for this breed and different genomic regions associated to the studied characteristics were identified.

Convergence of quantitative genetics and genomics is becoming the way that fundamental genetics and applied breeding will be carried out in the next decades. This study bridges the quantitative genetics of complex growth and wood properties traits with genomic technologies towards a more innovative approach to tree breeding. Planted forests play a major role to fulfill the growing world demand for wood products and energy. Eucalypts stand out for their high productivity and versatile wood resulting from the advanced breeding programs associated to clonal propagation and modern silviculture. Despite their fast growth, breeding cycles still take several years and wood properties assessment is limited to a sample of trees in the late stages of selection due to the costs involved in wood phenotyping, not exploitingthe range of genetic variation in wood properties. In this study, we examined fifteen traits including growth and wood chemical and physical properties in 1,000 individuals sampled from an elite Eucalyptus breeding population. Near-infrared spectroscopy (NIRS) models were developed and used for high-throughput phenotyping of wood traits.Highdensity data for 29,090 SNPs was used to obtain accurate pedigree-record-free estimates of trait variance components, heritabilities, genetic and phenotypic correlations, based on a realized relationship matrix, comparing them to pedigree-based estimates. To the best of our knowledge, this is the first study to do this in plants. NIRS predictions were accurate for wood chemical traits and wood density, and variably successful for physical traits. Heritabilities were medium for growth (0.34 to 0.44), high for wood chemical traits (0.56 to 0.85) and variable for wood physical traits (0.11 to 0.63). High positive correlations among growth traits and negative between cellulose and lignin content were observed, while correlations between wood chemical and physical traits and between growth and wood quality traits were low although significant. Phenotypes and SNP markers were then used to build genomic predictive models using a marker density higher than any previous genomic selection study in trees (1 SNP/21 kbp). Two models (RR-BLUP and Bayesian LASSO) that differ regarding the assumed distribution of marker effects were used for genomic predictions. Predictions were compared to those obtained by phenotypic BLUP. Predictive abilities very similar by the two models and strongly correlated to the heritabilities. Accurate genomic-enabled predictions were obtained for wood chemical traits related to lignin, wood density and growth, although generally 15 to 25% lower than those achieved by phenotypic BLUP prediction. Nevertheless, genomic predictions yielded a coincidence above 70% in selecting the top 30 trees ranked by phenotypic selection for growth, wood density and S:G ratio, and 60% when tandem selection was applied. The results of this study open opportunities for an increased use of highthroughput NIRS phenotyping and genome-wide SNP genotyping in Eucalyptus breeding, allowing accurate pedigree-record-free estimation of genetic parameters and prediction of genomic breeding values for yet to be phenotyped trees. These applications should become routine in tree breeding programs for the years to come, significantly reducing the length of breeding cycles while optimizing resource allocation and sustainability of the breeding endeavor. / A convergência da genética quantitativa com a genômica está se tornando a maneira pela qual a genética fundamental e aplicada serão conduzidas nas próximas décadas. Este estudo buscou conectar a genética de fenótipos complexos de crescimento e propriedades de madeira às tecnologias genômicas, em uma abordagem inovadora para o melhoramento florestal. Florestas plantadas têm papel fundamental para satisfazer a crescente demanda mundial por produtos madeireiros e energia. O eucalipto,com sua alta produtividade e madeira versátil, é resultado de programas avançados de melhoramento associados à propagação clonal e silvicultura moderna. Apesar de seu rápido crescimento, ciclos de melhoramento ainda levam muitos anos e a avaliação detalhada de propriedades da madeira é limitada a apenas uma amostra das árvores em estágios avançados de seleção, devido aos altos custos de fenotipagem, não explorando assim toda a variação genética disponível. Neste estudo, examinamos quinze caracteres, incluindo crescimento e propriedades químicas e físicas da madeira, em 1000 indivíduos amostrados de uma população elite de melhoramento. Modelos de espectroscopia de infravermelho próximo (NIRS) foram desenvolvidos e utilizados para fenotipagem de alto desempenho de propriedades de madeira. Genotipagem de alta densidade com 29.090 SNPs foi utilizada para obter estimativas acuradas de componentes de variância, herdabilidades e correlações genéticas baseadas em uma matriz de parentesco realizado, ou seja,sem o uso de pedigree. Este é o primeiro estudo de que temos conhecimento a fazer isso em plantas. Predições NIRS foram precisas para caracteres químicos da madeira e densidade, e apresentaram sucesso variável para caracteres físicos. As herdabilidades foram médias para crescimento (0,34 a 0,44), altas para caracteres químicos de madeira (0,56 a 0,85) e variáveis para caracteres físicos da madeira (0,11 a 0,63). Altas correlações positivas entre caracteres de crescimento e negativas entre celulose e lignina foram observadas, enquanto correlações entre caracteres químicos e físicos da madeira foram baixas, porém significativas. Fenótipos e marcadores SNP foram em seguida utilizados na construção de modelos preditivos com a maior densidade de marcadores já utilizada em estudos de seleção genômica em espécies florestais (1 SNP/21 kpb). Dois modelos de predição (RR-BLUP e LASSO Bayesiano)foram usados nas predições genômicas e comparados ao BLUP fenotípico. Os modelos apresentaram capacidades preditivas similares, fortemente correlacionadas às herdabilidades. Predições genômicas precisas foram obtidas para caracteres relacionados à lignina, densidade e crescimento, embora geralmente 15 a 25% menores do que as predições obtidas por BLUP fenotípico. Contudo, predições genômicas alcançaram coincidências acima de 70% na seleção das melhores 30 árvores ranqueadas pela seleção fenotípica para crescimento, densidade e relação S:G, e de 60% quando seleção em tandem foi aplicada. Os resultados deste estudo abrem enormes oportunidades para o uso combinado de fenotipagem NIRS e genotipagem com SNPs no melhoramento do eucalipto, permitindo estimativas acuradas de parâmetros genéticos e a predição de valores genéticos genômicos para plantas jovens ainda não fenotipadas. Estas aplicações deverão se tornar rotineiras nos programas de melhoramento florestal nos próximos anos, reduzindo significativamente a duração dos ciclos de seleção e, consequentemente, otimizando a alocação de recursos e a sustentabilidade do melhoramento.

New medical treatments, compounds that affect human health, nutritional supplements, and other substances, are introduced to society every day. The accurate determination of the potential toxicity from these substances is of critical importance to our society. Goals of the modern toxicologist not only involve the determination of the toxic potential of new substances but also: the elucidation of mechanisms; improving existing assays; and developing new assays to study toxicity. This thesis addresses these goals in two topics fundamental to toxicology. Re-evaluating the expression of dose and susceptibility of cells in culture The exposure of cells in culture to drugs, xenobiotics, and other compounds is one of the first tools used to determine the potential for toxicity. Problems can arise when results of these experiments are translated to next-level toxicity experiments (e.g. animals and humans). I hypothesized that "dose" in cell culture can be improved by designing and reporting experiments based on dose in moles per cell. When experiments were compared on an extracellular concentration basis, a large apparent variability in toxicity was observed. However, if these same exposures were expressed as moles per cell, all experiments yielded the same toxicity. In addition to the evaluation of mole per cell, I investigated the susceptibility of various cells to 1,4-benzoquinone. I hypothesized that upon exposure to toxins that bind covalently, larger cells would require more molecules per cell of toxin versus a smaller cell to achieve identical toxicities. I found a linear correlation between cell volume(pL) and ED50 (mole per cell where 50 % cell viability is lost), supporting my hypothesis. This work could improve current cell culture protocols and allow for better and less expensive determination of toxicities. Heritability of the red blood cell storage lesion Blood transfusions are an integral part of modern medicine with 5 million people receiving blood each year in the United States. There is growing evidence that red blood cells (RBCs) stored for longer periods are less therapeutically beneficial and could even be harmful to patients. This phenomenon of diminished RBC function with increased time in storage is called the storage lesion. However, there is great variation between different donors in the severity of the storage lesion in their donated RBCs. I hypothesized that part of this variability in the RBC storage lesion is determined by heritable genetic differences. To test this hypothesis, a study using mono- and di-zygotic twins was performed to determine the heritability of adenosine triphosphate (ATP), glutathione (GSH), glutathione disulfide (GSSG) and hemolysis in stored blood. Major discoveries in this study include: GSH, GSSG, and the half-cell reduction potential (Ehc) are heritable (57 %, 51 %, and 70 %, respectively) in non-stored RBCs. In addition, ATP was found to be heritable in two different storage solutions (62 % in AS-3, 71 % in CP2D); as well as GSH, GSSG, Ehc and hemolysis (59 %, 48 %, 64 %, and 53 %, respectively). These discoveries could eventually be used to develop new genetic tests that would predict the rate of deterioration in stored blood quality on an individual basis.

Genome-wide association studies (GWAS) are a tool of high importance to associate genetic markers, genes and genomic regions with complex phenotypes and diseases, allowing to understand in details this regulation of gene expression as well as the genes, and then develop new techniques of diagnoses and treatment of diseases. Nowadays, the main genetic marker used in GWAS is the SNP (single nucleotide polymorphism), a variation that affects only one base of the DNA, being the most common type of variation between individuals and inside the genome. Even though there are multiple techniques available for GWAS, several complex traits still have unexplained heritability. To contribute to these studies, reference genetic maps are being created, such as the HapMap and 1000 Genomes, which have common genetic variants from world wide population (including European, Asian and African populations). In the last years, two solutions adopted to solve the missing heritability are to use different types of genetic variants and include the rare and population specific markers. Copy number variation (CNV) is a structural variant which use is increasing in GWAS in the last years. This variant is characterized for the deletion or duplication of a region a DNA and its length can be from few bases pair to the whole chromosome, as in Down syndrome. In collaboration of the Heart Institute (InCor-FMUSP), this work uses the dataset from Baependi Heart Study to establish a methodology to characterized the CNVs in the Brazilian population using SNP array data and associate them with height. This project uses the genetic and phenotype data of 1,120 related samples (family structure). For CNV calling, resources from the software PennCNV are used and methodologies of preprocessing, normalization, identification and other analysis are reviewed. The characterization of CNVs include information about location, size, frequency in our population and the patterns of inheritance in trios. The association of CNVs and height is made using linear mixed models and with information of family structure. The obtained results indicate that the Brazilian population has regions with variation in the number of copies that are not in the literature. General characteristics, such as length and frequency in samples, are similar to the information found in the literature. In addition, it was observed that the transmission of CNVs could not follow the Mendelian laws, since the frequency of trios which one parent has a deletion/duplication and the offspring is normal is higher than the frequency of trios with one parent and the offspring has a deletion/duplication. This work also identified a region on chromosome 9 that could be associated to height, being that carries of a duplication in this region can have the expected height dropped by approximately 3cm. / Estudos de associação genética (do inglês, Genome-wide association studies - GWAS) são uma ferramenta fundamental para associar marcadores genéticos, genes e regiões genômicas com doenças e fenótipos complexos, permitindo compreender em mais detalhes essa rede de regulação bem como mapear genes e, com isso, desenvolver técnicas de diagnóstico e tratamento. Atualmente, a principal variante genética utilizada nos estudos de associação é o SNP (do inglês, Single Nucleotide Polymorphism), uma variação que afeta apenas uma base do DNA, sendo o tipo de variação mais comum tanto entre os indivíduos como dentro do genoma. Apesar das diferentes técnicas disponíveis para os estudos de associação, muitas doenças e traços complexos ainda possuem parte de sua herdabilidade inexplicada. Para contribuir com estes estudos, foram criados banco de dados genéticos de referência, como o HapMap e o 1000 Genomes, que possuem representantes das variantes genéticas comuns das populações mundiais (européias, asiáticas e africanas). Nos últimos anos, duas das solucões adotadas para tentar explicar a herdabilidade de doenças e fenótipos complexos correspondem a utilizar diferentes tipos de variantes genéticas e incluir variantes raras e específicas para uma determinada população. O CNV (do inglês, Copy Number Variation) é uma variante estrutural que está ganhando espaço nos estudos de associação nos últimos anos. Essa variante é caracterizada pela deleção ou duplicação de uma região do DNA que pode ser de apenas alguns pares de bases até cromossomos inteiros, como no caso da síndrome de Down. Em parceria com o Instituto do Coração (InCor-FMUSP), este trabalho utiliza os dados do projeto Corações de Baependi para estabelecer uma metodologia para caracterizar os CNVs na população brasileira a partir de dados de SNPs e associá-los com a altura. O projeto inclui dados genéticos e fenótipos de 1,120 indivíduos relacionados (estruturados em famílias). Para a detecção dos CNVs, os recursos do software PennCNV são utilizados e metodologias de processamento, normalização, identificação e análises envolvidas são revisadas. A caracterização dos CNVs obtidos inclui informações de localização, tamanho e frequência na população e padrões de herança genética em trios. A associação dos CNVs com a altura é realizada a partir de modelos lineares mistos e utilizando informações sobre a estrutura de família. Os resultados obtidos indicaram que a população brasileira contém regiões (únicas) com variação no número de cópias que não estão identificadas na literatura. Características gerais dos CNVs, como tamanho e frequência no indivíduo, foram semelhantes ao que é apontado na literatura. Também foi observado que a transmissão de CNV pode não seguir as leis mendelianas, uma vez que a frequência de trios com um dos pais com deleção/duplicação e filho normal era superior à frequência dos trios com filho portador da mesma variação.

La réponse des arbres à l'augmentation des sécheresses liées au réchauffement climatique dépend de leur capacité d'adaptation, c’est-à-dire de la variation génétique et de l’héritabilité de caractères adaptatifs impliqués dans la résistance à la sécheresse. Dans le chapitre I, nous identifions des proxys facilement mesurables de caractères adaptatifs impliqués dans la résistance à la sécheresse en comparant la microdensité du bois d’individus morts et survivants après la sécheresse de 2003. Les variables les plus discriminantes sont les densités moyennes de segments de haute et basse densité, la proportion du segment de haute densité et le coefficient de variation du segment de haute densité. Les arbres survivants ont toujours une densité plus élevée et des profils généralement plus hétérogènes. Si ces traits sont suffisamment variables génétiquement et héritables, alors il est possible de sélectionner des arbres plus résistants à la sécheresse dans les populations d'amélioration et dans les peuplements forestiers destinés à être régénérées naturellement. Nos résultats suggèrent qu’une sélection naturelle directionnelle pour la densité du bois du douglas se produit dans des environnements plus ou moins limités en eau. Cette sélection agit dans des directions différentes selon les caractéristiques des pressions de sélections subies dans les régions étudiées. Dans le chapitre II, nous évaluons le potentiel d’adaptation à la sécheresse du douglas introduit en France. Ce potentiel d’adaptation dépend de la variation génétique et de l'héritabilité des caractères adaptatifs mis en évidence dans le chapitre I. Nous trouvons une grande variabilité des estimations d’héritabilité et d’AGCV entre variables, provenances, sites et, dans une faible mesure, entre cernes annuels. La plupart des variables possèdent des héritabilités élevées à assez élevées au moins pour certaines provenances dans certains sites. Certaines variables tendent à avoir des héritabilités et AGCV généralement plus élevées : ce sont plutôt des variables de la partie de faible densité du cerne. Certaines variables de résistance à la sécheresse possèdent à la fois une héritabilité et une AGCV élevées : ce sont de bons critères de sélection pour la résistance à la sécheresse en amélioration génétique ou en régénération naturelle. Les estimations différentes entre sites suggèrent que les estimations d’héritabilités augmentent avec le caractère favorable du milieu. Les estimations sont significativement différentes entre provenances, avec de forts effets d’interaction avec les sites. En revanche il y a peu ou pas de différences significatives entre cernes. Dans le chapitre III, nous avons tenu compte de la variation associée aux cernes de croissance pour étudier les relations entre les estimations annuelles de paramètres génétiques et des variables climatiques et édaphiques. Les estimations d'héritabilité et de variation génétique de la plupart des variables de microdensité sont corrélées significativement avec la plupart des variables environnementales testées. De rares variables n’ont montré aucune corrélation significative dans aucun cas. Les caractéristiques des relations significatives sont variables entre les caractères, les sites et les provenances. Les prédicteurs climatiques les plus importants sont la température, l'évapotranspiration, la réserve en eau du sol et le déficit en eau. Les précipitations affectent peu l´estimation des paramètres génétiques. De façon générale, meilleures sont les conditions de croissance, plus élevées sont les estimations. Toutes les composantes des essais expérimentaux modifient les estimations des paramètres génétiques. Certaines peuvent être fortement déterminées par le choix du matériel végétal et du site. D'autres, comme la variation climatique temporelle, sont moins contrôlées et peuvent affecter de façon plus ou moins aléatoire les estimations. / Forest response to the drought increase associated to the climatic warming relies on tree adaptive potential, i.e. the genetic variation and the heritability of adaptive traits involved in resistance to drought. In the first chapter, we identify easy-to-measure proxies of adaptive traits for resistance to drought. We compare the wood microdensity of dead and surviving trees after the 2003 heat wave in France. The most discriminating variables are the mean density of high and lowdensity segments, high-density proportion and coefficient of variation of the lowdensity segment. The wood of the surviving trees is always denser and more heterogeneous. If these adaptive traits are variable and heritable, then it is possible to select for improved resistance to drought in the breeding population as well as in natural regeneration. Our results also suggest that directional selection is going on in more or less water-stressed environments. The direction is variable according to the nature of the selection pressure in the different regions. In the Chapter II, we estimate the evolutionary potential to drought of the introduced Douglas-fir in France. This evolutionary potential relies on the magnitude of the genetic variation and of the heritability of the adaptive traits found in the first chapter. The heritability and the genetic variation are highly variable between provenances, sites and, to a much lower extent, between annual rings. Most variables have moderate to high heritability estimates for at least some provenances in some sites. Some traits tend to have generally higher heritability and genetic variation estimates. These are mostly variables of the density part of the annual ring. The variables having at the same time relatively high estimates of heritability and genetic variation are good candidates for becoming efficient selection traits for resistance to drought in tree breeding as well as in natural regeneration. The significant between-site variation suggests that the heritability estimates increase with site quality. The estimates are also significantly different between provenances with a strong provenance × site interaction. Conversely there is little significant between annual-ring variation. The chapter III takes advantage of the annual-ring variation to study the relationships between the genetic parameter estimates and climatic and soil variables. The heritability and genetic variation estimates of most variables significantly relates with most tested environmental variables. Very few variables never correlates with any environmental variable. The significant relationships are very variable between traits, provenances and sites. The most important predictors are temperature, evapotranspiration, and soil water reserve and water deficit. Rainfall marginally influences the genetic parameter estimates. Generally, the better the growing conditions, the higher the estimates. All components of the experimental trials affect the genetic parameters estimates. Thus, the choice of the plant material and of the experimental site strongly determines the genetic parameter estimates. The uncontrolled climatic variation may randomly affect the estimates.

Orientador: Ana Fabrícia Braga Magalhães / Resumo: ABSTRACT – Preweaning calf mortality is one of main causes of economic losses in beef cattle, since most of economic incomes are represented by the number of weaned calves available for sale. It is also detrimental for genetic progress due to the reduction of young candidates for selection. The inclusion of molecular markers in genetic analysis allows a better understanding of genetic mechanisms underlying calf mortality. The objectives of this study were: i) to estimate direct and maternal heritability of preweaning calf mortality in Nellore cattle and ii) to seek for genomic regions and candidate genes affecting direct and maternal effects of preweaning calf mortality in Nellore cattle. Variance components were estimated via Bayesian Inference using a threshold animal model, that included the systematic effects of contemporary group, birth weight as linear covariate, and age of dam at calving as linear and quadratic covariates. The direct and maternal genetics, and the residual were fitted as random effects. The final dataset used contained phenotypic records on 67,196 animals, offspring of 1,469 sires and 30,970 dams. The SNPs effects were estimated based on the weighted single-step GBLUP approach, using information of 8,443 genotyped animals with 410,936 SNPs. Direct and maternal heritability estimates were of 0.2143±0.0348 and 0.0137±0.0066, respectively. The top 10 genomic regions accounted for 13.61 and 14.23% of direct and maternal additive genetic variance and harbor... (Resumo completo, clicar acesso eletrônico abaixo) / Mestre

Sweden and Norway have the worldwide highest incidence of osteoporotic fractures. As these fractures constitute a tremendous and growing problem, primary prevention is of great importance. The principal causes of an osteoporotic fracture are a fall and a fragile skeleton. The aim of the studies reported in these papers was therefore to determine the genetic and environmental influences on fractures and the genetic influence on the two main reasons to the emergence of osteoporotic fractures; bone mineral density and propensity to fall. In the present thesis, we display that the heritability of fractures is dependent on fracture site and age. With increasing age, lifestyle becomes the dominant explanatory factor. These results indicate that focus should be on lifestyle interventions for the prevention of fractures in the elderly. Although the genetic liability to impaired balance is modest, twins with self-reported impaired balance have a substantially increased risk of osteoporotic fractures compared to their co-twin without impaired balance. Asking a patient about his or her balance might be a simple tool for future risk assessment. The genetic influence on bone phenotypes is under strong genetic influence in Swedish adult twins. These findings are in agreement with the results from previous studies in other countries, with a lower incidence of osteoporotic fractures compared to Sweden. The high heritability of bone phenotypes together with the low heritability of fractures at old age, indicates that bone mineral density has a modest influence on fracture risk at old age. In summary, based on the results in this thesis, more emphasis should be targeted to the prevention of falls, by strength and balance training in order to prevent the occurrence of  low energy fractures in the elderly.

Grain quality in chickpea (<i>Cicer arietinum</i> L.) is a major factor affecting its consumption for human nutrition and health benefits. Some of the major factors affecting chickpea grain quality are: seed weight, size, colour, protein, starch and amylose concentration, and amylopectin structure. The objectives of this study were to: 1) determine variation, repeatability and genotype by environment interaction on thousand seed weight, starch, amylose and protein concentration of chickpea cultivars adapted to western Canada; 2) assess variations in global chickpea germplasm for thousand seed weight, seed size, protein, starch and amylose concentrations; and 3) characterize the desi and kabuli type chickpea for starch concentration, composition, and amylopectin structure to study their effect on starch enzymatic hydrolysis. Limited variation was observed in seed composition of chickpea cultivars adapted to the western Canadian prairies. Significant genotype by environment interaction occurred for starch, amylose, and protein (except for kabuli) concentrations, seed yield and thousand seed weight indicating that testing over a wide range of environments is needed to identify genotypes for grain quality improvement. Repeatability of starch, amylose, and protein concentrations was low and inconsistent across chickpea market classes. Broad sense heritability was higher than repeatability across all traits for all market classes implying that repeatability estimates do not set upper limits to heritability if significant genotype by environment interaction is present. The negative relationship between seed constituents and yield indicates that selection for chickpea cultivars with desired seed composition may require compromise with yield and indirect selection. All the mini core accessions that had above average seed diameter score in both desi and kabuli also had above average score for thousand seed weight. Selecting mini core with promising intrinsic and extrinsic quality characteristics may reduce yield. Slowly digestible starch was negatively correlated with hydrolysis index in both pure starch and meal starch of desi and kabuli. Amylose had a strong relationship with resistant starch but not with rate of starch hydrolysis. Genotypes with a significantly higher rate of starch hydrolysis had significantly lower 60-80 µm starch granule size volume. Amylopectin B2 chains were related to slowly digestible starch of meal (except kabuli) and extracted starch. Resistant starch positively correlated with B1 fraction of amylopectin chain length in both desi and kabuli meal starch. Our results suggest that there is no major difference between starch composition in the two chickpea market classes, although only three genotypes of each class were tested. The meal components affect the starch hydrolytic properties and the effect is genotype specific. The results also show that amylopectin structure influences starch hydrolytic properties. These observations emphasize that complete characterization of seed components is needed to obtain meaningful results regarding the desired nutritional and health benefits attributed to any grain.