Across vertebrates, skeletal shapes are diverse, and much of this variation appears to be adaptive. In contrast, the early developmental programs of these structures are highly conserved across vertebrates. The question then becomes where in the conserved genetic programs of skeletal development does variation lie to direct diversity? In threespine stickleback, rapid changes in head and body shape have been documented during repeated and independent invasions of oceanic fish into freshwater habitats in regions deglaciated approximately 13,000 years ago. However, recent research indicates that similar phenotypic and genetic divergence can occur in decades. A remaining challenge is to link stickleback population genomic variation to causal genes that underlie such rapid phenotypic evolution. Here I use genome wide association studies (GWAS) in natural populations of stickleback to uncover genomic regions that contribute to variation of two dermal bone derived traits, lateral plate number and opercle shape. The decrease of lateral plate body armor and change in opercle bone shape, important for feeding mechanics, are classically associated with freshwater divergence. GWAS has recently begun to be used in natural populations but is still under scrutiny for performance among different populations. Using a population of phenotypically variable stickleback in Oregon, GWAS proved an effective method to uncover genomic regions and genetic variants known to contribute to lateral plate number and opercle shape, as well as new genomic regions and candidate genes not previously implicated in phenotypic variation. Although successful, using similar methods on decades old stickleback populations in Alaska revealed the challenges that accompany controlling population structure created by strong natural selection. Together, I found that although lateral plate number and opercle shape rapidly evolve in a coordinated fashion during adaptation from marine to freshwater environments, phenotypic variation is largely driven by independent genetic architectures. However, in very rapidly evolving populations, despite this independence of genetic architecture, the genetic variants contributing to the traits co-localize to similar genomic regions. This finding could be either biological or methodological which highlights the promise and limitations of using GWAS to identify genetic variation that gives rise to phenotypic diversity. This dissertation includes unpublished co-authored material.

Orientador: Alexandre Magno Sebbenn / Resumo: In Uruguay, reforestation with Eucalyptus sp. is of fundamental importance to produce paper, pulp and wood. The productivity of these continually grows due to application of breeding techniques, such as hybridization. This study aimed to investigate genetic parameters, productivity, stability, adaptability and to identify SNP markers associated with the diameter breast height (DBH) for to select Eucalypts grandis x Eucalyptus globulus full-sibs hybrid clones. The study was conducted in a clonal test, repeated at two different soils, in the state of Rio Negro, Uruguay. The population was phenotypically characterized to the DBH at 48 months of age and cambium tissues of each individual were sampled for genotyping with EuCHIP60K chip. The mean growth in DBH was similar between both places. The genotype-environment interaction was the simple type, with high genotype correlation in clones’ performance between environments (0.708), indicating the possibility of the same clones being selected for both places. Mean heritability between clones (0.724), coefficient of individual genetic variation (10.9%) and relative variation (0.916), showed the possibility of obtaining gains by selecting clones with higher growth, which was estimated in 3.1% for both sites together. A total of 15,196 markers SNPs were used in the genomic selection for the DBH, but after cleaning of SNPs data, the number was reduced for 15,196 (23.5%). The predictive capacity was expected to be low or negative (-0.15)... (Resumo completo, clicar acesso eletrônico abaixo) / Doutor

Submitted by DANIELA BARRETO AMARAL TEIXEIRA null (danielabateixeira@hotmail.com) on 2016-07-09T12:26:08Z No. of bitstreams: 1 DissertaçãoDaniela.pdf: 1505420 bytes, checksum: b57087f798762d84c029781714eac7b5 (MD5) / Approved for entry into archive by Ana Paula Grisoto (grisotoana@reitoria.unesp.br) on 2016-07-12T16:54:26Z (GMT) No. of bitstreams: 1 teixeira_dba_me_jabo.pdf: 1505420 bytes, checksum: b57087f798762d84c029781714eac7b5 (MD5) / Made available in DSpace on 2016-07-12T16:54:26Z (GMT). No. of bitstreams: 1 teixeira_dba_me_jabo.pdf: 1505420 bytes, checksum: b57087f798762d84c029781714eac7b5 (MD5) Previous issue date: 2016-06-20 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / A habilidade de permanência (HP), que pode ser definida como a probabilidade de uma vaca parir numa determinada idade, dado que ela teve esta oportunidade, é uma característica reprodutiva de grande importância em bovinos de corte, estando diretamente relacionada à produtividade do rebanho. O objetivo deste trabalho foi estimar parâmetros genéticos e identificar possíveis regiões do genoma que estejam associadas com a expressão fenotípica da HP de vacas da raça Nelore. Os componentes de variância foram estimados por inferência bayesiana utilizando um modelo de limiar no qual foram considerados os efeitos sistemáticos de grupos de contemporâneos e precocidade sexual, e os efeitos aleatórios de animal e resíduo.Os efeitos dos SNPs foram estimados por meio da metodologia ssGBLUP, sendo utilizados na análise 2838 animais genotipados com o painel de alta densidade da Illumina (Bovine HD Assay Illumina, San Diego, CA, USA). A variância explicada por janelas formadas por 200 SNPs consecutivos foi utilizada na identificação das regiões de maior efeito sobre a expressão da característica HP. A herdabilidade encontrada utilizando a matriz A (pedigree) foi de 0,11±0,01 e utilizando a matriz H( matriz de parentesco que combina a informação de pedigree e dos SNPs) de 0,14±0,01. Foram encontrados 147 genes candidatos para a característica habilidade de permanência em regiões dos cromossomos 1, 2, 5, 6, 9, 20 e no cromossomo sexual X. Novas regiões candidatas para a característica habilidade de permanência foram detectadas e a maioria está relacionada a funções reprodutivas, imunológicas e ligadas ao sistema nervoso. / Stayability, which can be defined as the probability of a cow calving to a certain age since it has this opportunity, is a reproduction trait of great importance in beef cattle and is directly related to the productivity of the herd. The objective of this study was to estimate variance components through single-step G-BLUP methodology, and use the solutions of the SNPs effects to identify possible regions of the genome that are associated with the phenotypic expression of stayability in Nellore cows. The variance components were estimated by Bayesian inference using a threshold model in which were considered the fixed effects of precocity and contemporary groups, and the random effects of residue and animal. The effects of SNP were estimated by ssGBLUP methodology being used for the analysis 2838 animals genotyped with the Illumina panel of high density ( HD Assay Bovine Illumina, San Diego, CA , USA ). A Manhattan plot containing the variance explained by the windows formed by 200 SNPs consecutive was used to identify regions of greatest effect on the expression of stayability trait. The heritability found using the A matrix was 0.11 ± 0.01 and using the H matrix was 0.14 ± 0.01. 147 potential genes for stayability were found in regions of chromosomes 1,2,5,6,9,20 and sexual chromosome X. New candidate regions for stayability were detected and most of them are related to reproductive, immune and nervous system. / FAPESP: 2009/16118-5

abstract: A variety of studies have shown that the tendency toward nicotine dependence has a genetic component. The work described in this thesis addresses three separate questions: i) are there unidentified SNPs in the nicotinic receptors or other genes that contribute to the risk for nicotine dependence; ii) is there evidence of ongoing selection at nicotinic receptor loci; and, iii) since nicotine dependence is unlikely to be the phenotype undergoing selection, is a positive effect on memory or cognition the selected phenotype. I first undertook a genome –wide association scan of imputed data using samples from the Collaborative Study of the Genetics of Nicotine Dependence (COGEND). A novel association was found between nicotine dependence and SNPs at 13q31. The genes at this newly associated locus on chromosome 13 encode a group of micro-RNAs and a member of the glypican gene family. These are among the first findings to implicate a non-candidate gene in risk for nicotine dependence. I applied several complimentary methods to sequence data from the 1000 Genomes Project to test for evidence of selection at the nicotinic receptor loci. I found strong evidence for selection for alleles in the nicotinic receptor cluster on chromosome 8 that confer risk of nicotine dependence. I then used the dataset from the Collaborative Studies on the Genetics of Alcoholism (COGA) and looked for an association between neuropsychological phenotypes and SNPs conferring risk of nicotine dependence. One SNP passed multiple test correction for association with WAIS digit symbol score. This SNP is not itself associated with nicotine dependence but is in reasonable (r 2 = 0.75) LD with SNPs that are associated with nicotine dependence. These data suggest at best, a weak correlation between nicotine dependence and any of the tested cognitive phenotypes. Given the reproducible finding of an inverse relationship between SNPs associated with risk for nicotine dependence and cocaine dependence, I hypothesize that the apparently detrimental phenotype of nicotine dependence may confer decreased risk for cocaine dependence. As cocaine use impairs the positive rewards associated with social interactions, reducing the risk of cocaine addiction may be beneficial to both the individual and the group. / Dissertation/Thesis / Ph.D. Anthropology 2014

Submitted by Marlene Santos (marlene.bc.ufg@gmail.com) on 2016-06-08T20:29:50Z No. of bitstreams: 2 Tese - Alex Silva da Cruz - 2015.pdf: 4189617 bytes, checksum: f21e8815a51e44f144dd811005f32bdd (MD5) license_rdf: 19874 bytes, checksum: 38cb62ef53e6f513db2fb7e337df6485 (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2016-06-09T11:41:47Z (GMT) No. of bitstreams: 2 Tese - Alex Silva da Cruz - 2015.pdf: 4189617 bytes, checksum: f21e8815a51e44f144dd811005f32bdd (MD5) license_rdf: 19874 bytes, checksum: 38cb62ef53e6f513db2fb7e337df6485 (MD5) / Made available in DSpace on 2016-06-09T11:41:47Z (GMT). No. of bitstreams: 2 Tese - Alex Silva da Cruz - 2015.pdf: 4189617 bytes, checksum: f21e8815a51e44f144dd811005f32bdd (MD5) license_rdf: 19874 bytes, checksum: 38cb62ef53e6f513db2fb7e337df6485 (MD5) Previous issue date: 2015-10-19 / Fundação de Amparo à Pesquisa do Estado de Goiás - FAPEG / Genomic selection in a dairy cattle breeding is a new strategy in national livestock. Genome wide association study (GWAS) is known as a strategy that involve the use of molecular markers panels distributed throughout the genome which are selected for the identification of chromosomal regions that are important for the interest traits. The aim of this study was apply the GWAS strategy for 305-day milk yield in Girolando cows. We did the genotype from 404 Girolando and after quality control analysis remained 337 individuals and 45.622 markers. The GWAS analysis resulted in 52 SNPs associated to 305-day milk yield. Of these, 23 SNPs were linked to Known genes and only 3 SNPs were linked to NUB1, SLC24A2 and DGAT1 genes that already were associated with cattle lactation. The other SNPs have no relationships described in the cattle lactation literature. In addition, the milk production QTL analysis resulted in 52 SNPs and 14 genes linked or close to 1Mb of the SNP marker. The ARS-BFGL-NGS-414 SNP on BTA19 at 47.9Mbp is located near to GH1 gene. This gene is commonly accepted as causal gene for Quantitative Character Locus of milk production mainly affecting the yield in liters and solid milk components. Thus, our data suggest that NUB1 and SLC24A2 genes could be considered as candidate genes to understand the milk production in Girolando breed. Like this DGAT1 and GH1 genes are valuable predictive markers to be added to genomic selection of dairy cattle in breeding program. / A seleção genômica, aplicada em bovino em associação à produção de leite é uma inovação estratégica na pecuária nacional, e que poderá se tornar uma ferramenta prática importante para a atividade. Estudos de Associação Ampla do Genoma (GWAs) caracteriza-se como uma estratégia que envolve o uso de painéis de marcadores moleculares distribuídos por todo o genoma, selecionados para a identificação de regiões dos cromossomos associadas com um fenótipo de interesse. O objetivo deste estudo foi aplicar a estratégia de GWAS para a característica de lactação total ajustada em 305 dias de vacas Girolando. Inicialmente, foram genotipados 404 vacas Girolando que após procedimento de controle de qualidade resultou em um total de 337 indivíduos e 45.622 marcador. O GWAS resultou em 52 SNPs associados a lactação ajustada em 305 dias. Destes, 23 SNPs apresentaram-se ligados a genes conhecidos e somente 3 SNPs estão ligados aos genes NUB1, SLC24A2 e DGAT1, descritos relacionados a lactação em bovinos. Os demais SNPs não apresentam relações descrita na literatura a lactação em bovinos. Para o QTL de produção de leite (MY), dos 52 SNPs, foram identificados 14 genes ligados ou próximos a 1Mb de distância do SNP marcador. Em particular, o SNP ARS-BFGL-NGS-414 associado ao QTL de lactação bovina, constituído de aproximadamente 47,9 Mbp localizado no BTA19 está localizado muito próximo do gene GH1 (Hormônio do Crescimento 1), comumente aceito como gene causal para o Lócus de Caráter Quantitativo (QTL) de produção de leite, afetando principalmente o rendimento em litros e componentes sólidos do leite. Dessa forma, nossos dados sugerem que os genes NUB1, e SLC24A2 poderiam ser considerados como genes candidatos para ajudar a explicar a produção de leite em animais da raça Girolando, assim como os genes DGAT1 e GH1, são considerados como valiosos marcadores preditivos a serem adicionados à seleção genômica do gado leiteiro em programas de melhoramento.

Submitted by Gabriela Lopes (gmachadolopesufpel@gmail.com) on 2018-05-24T17:18:08Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Thesis Liane_Final version.pdf: 4719459 bytes, checksum: 27c7e78c16dd0cfaf24b4611c1aff8ff (MD5) / Approved for entry into archive by Aline Batista (alinehb.ufpel@gmail.com) on 2018-05-30T12:53:36Z (GMT) No. of bitstreams: 2 Thesis Liane_Final version.pdf: 4719459 bytes, checksum: 27c7e78c16dd0cfaf24b4611c1aff8ff (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2018-05-30T12:53:36Z (GMT). No. of bitstreams: 2 Thesis Liane_Final version.pdf: 4719459 bytes, checksum: 27c7e78c16dd0cfaf24b4611c1aff8ff (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2018-03-14 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / O pessegueiro (Prunus persica) é uma das espécies decíduas geneticamente melhor caracterizadas e a terceira frutífera mais importante de clima temperado em todo o mundo. A cultura é vulnerável à bacteriose causada pelo patógeno Xanthomonas arboricola pv. pruni (Xap) e o melhoramento genético visando resistência têm sido a melhor forma de controle da doença. Com o objetivo de contribuir para desenvolvimento de cultivares com maior resistência e implementar análises de associação genômica ampla (GWAS), foi explorado o uso de genotipagem por sequenciamento (GBS) para descoberta e genotipagem simultânea de SNPs em larga escala e realizada caracterização fenotípica para resposta à Xap, em um painel de 220 genótipos de pessegueiro, representativos do germoplasma disponível para melhoramento no Brasil. Um total de 93.353 marcadores SNPs foram descobertos e após filtragem de alta qualidade 18.373 SNPs foram utilizados. Destes, 34% estavam localizados em regiões genômicas, sendo 70% destes em regiões codificantes. Foi detectada forte estrutura genética de população e a distribuição dos genótipos dentro de subpopulações baseou-se principalmente em características relacionadas à fruta: polpa fundente e polpa não-fundente. Padrões de desequilíbrio de ligação (LD) sugeriram uma queda média de LD em relação à distância e a extensão do LD altamente dependente da subpopulação e das regiões do genoma. Avaliações de campo e através do bioensaio de folhas destacadas mostraram resultados confiáveis e complementares para identificar fontes resistentes à Xap. Os genótipos 'Norman', 'Cristal Taquari', 'La Feliciana' e 'Precocinho' foram considerados fontes altamente resistentes e podem ser alternativas efetivas para melhorar a resistência à Xap em pessegueiro. Em geral, o germoplasma avaliado mostrou grande variabilidade para resposta à Xap, permitindo a identificação de genótipos contrastantes para a característica de interesse. Os genótipos com resistência podem ser preferencialmente utilizados em áreas de produção com maior ocorrência da doença, ou utilizados como genitores no programa de melhoramento visando aumentar o nível de resistência. Análises de GWAS validaram e definiram com mais precisão as regiões genômicas identificadas com resistência ao patógeno em estudos anteriores, bem como possibilitaram a identificação de novos genes candidatos que necessitam ser melhor ix estudados. Vários SNPs informativos foram funcionalmente anotados em genes envolvidos em mecanismos de defesa à infecção por patógenos, com destaque para duas regiões genômicas, localizadas no cromossomo 1 (2,59 Mpb) e 2 (2,85 Mpb), respectivamente, ambas identificadas com vários genes R. Os resultados encontrados abrem novos caminhos para o melhoramento genético visando resistência a Xap, com grande potencial para subsequente aplicação de seleção assistida por marcadores. / Peach (Prunus persica) is one of the best genetically characterized deciduous trees and the third most important temperate fruit crop worldwide. This crop is vulnerable to bacterial spot caused by Xanthomonas arboricola pv. pruni (Xap) and breeding for resistance has been the main choice to control the disease. With the aim to contribute with breeding for more resistant cultivars, and perform genome-wide association analysis (GWAS), we explored the use of genotyping by sequencing (GBS) for large-scale SNP discovery and simultaneous genotyping and performed high quality phenotyping for Xap response, among a panel with 220 peach genotypes, representative of the Brazilian breeding germplasm. A total of 93,353 SNP markers were discovered, and after filtering 18,373 high quality SNPs were used in analyses. Thirty-four percent of selected SNPs were located in genic regions and 70% of these in the coding sequence. Strong population genetic structure was detected, with the distribution of genotypes within subpopulations based mainly on fruit-related traits: melting and non-melting flesh. Linkage disequilibrium (LD) patterns suggested a medium LD level, with the extent of LD highly dependent on the subpopulations and genome regions. Field evaluation and detached leaf assessments were reliable and complementary methods to identify Xap resistant sources. The genotypes ‘Norman’, ‘Cristal Taquari’, ‘La Feliciana’ and ‘Precocinho’ were considered highly resistant sources and may be effective alternatives to improve Xap resistance in peach. Overall, the germplasm evaluated showed great variability for response to Xap, allowing the identification of contrasting genotypes for the trait of interest. Genotypes with resistance could be preferred for peach production areas more subjected to disease occurrence, or used as parents by the breeding program to improve resistance. GWAS analysis validated and defined more accurately the known genomic regions underlying Xap resistance, as well as identified novel candidate genes that provide useful targets for further investigation. Several informative SNPs were functionally annotated in genes involved in defense mechanisms against pathogen infection, highlighting two genomic regions, located on chromosome 1 (2.59 Mbp) and 2 (2.85 Mbp), respectively, both housing several R genes. Our results provide new insights into breeding for Xap resistance in peach, with great potential for subsequent application of marker-assisted selection.

No description available.

Orientador: Josineudson Augusto II de Vasconcelos Silva / Resumo: A raça Gir (Bos indicus) é importante recurso genético para produção de carne e leite no Brasil e em países tropicais. Estudos genômicos entre populações são de interesse para identificar regiões genômicas importantes e aplicar na seleção de caraterísticas de produção. As corridas de homozigose (ROH) são regiões homozigotas contíguas do genoma, utilizadas na identificação de genes associados a características de interesse econômico, bem como na obtenção dos coeficientes de endogamia. A interação genótipo ambiente (IGA), também representa papel importante no estudo de populações de bovinos e na seleção dos melhores reprodutores para os diferentes ambientes. Com isto, os objetivos do presente estudo foram analisar o comprimento e a distribuição das ilhas ROH do genoma, com identificação dos gene presentes, além de avaliar a acurácia da imputação utilizando diferentes painéis comerciais e a interação genótipo ambiente da produção de leite em bovinos da raça Gir do Brasil e Colômbia. Na avaliação das ilhas ROH foram utilizados dados genotípicos de 173 animais selecionados para produção de carne e 291 animais selecionados para produção leiteira e obtidos os resultados via programa Plink. Análise da acurácia utilizando diferentes painéis de SNPs (GGP Bovine 30K, GGP indicus 35K e HD 777K) de 464 animais do Brasil e da Colômbia foram avaliados e os resultados comparados via correlação simples (CS) e taxa de concordância (CR). Na análise da IGA foi utilizado modelo de norma de reação... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The Gir breed (Bos indicus) is an important genetic resource for meat and milk production in Brazil and in tropical countries. Genomic studies between populations are of interest to identify important genomic regions and apply in the selection of production traits. Runs of Homozygosity (ROH) are contiguous homozygous regions of the genome, used to identify genes associated with characteristics of economic interest, as well as to obtain inbreeding coefficients. The environment genotype (IGA) interaction also plays an important role in the study of bovine populations and in the selection of the best breeders for different environments. Thus, the objectives of the present study were to analyze the length and distribution of the ROH islands of the genome, with identification of the present genes, in addition to assessing the accuracy of imputation using different commercial panels and the environment genotype interaction of milk production in cattle of the Gir breed from Brazil and Colombia. In the evaluation of the ROH islands, genotypic data from 173 animals selected for beef production and 291 animals selected for milk production were used and the results were obtained through the Plink program. Accuracy analysis using different SNP panels (GGP Bovine 30K, GGP indicus 35K and HD 777K) from 464 animals from Brazil and Colombia were evaluated and the results were compared using simple correlation (CS) and concordance rate (CR). The IGA analysis used a bi-traits reaction standard... (Complete abstract click electronic access below) / Doutor

In this project, two different machine learning models were tested in an attempt at imputing missing genotype data from patients on two different panels. As the integrity of the patients had to be protected, initial training was done on data simulated from the 1000 Genomes Project. The first model consisted of two convolutional variational autoencoders and the latent representations of the networks were shuffled to force the networks to find the same patterns in the two datasets. This model was unfortunately unsuccessful at imputing the missing data. The second model was based on a UNet structure and was more successful at the task of imputation. This model had one encoder for each dataset, making each encoder specialized at finding patterns in its own data. Further improvements are required in order for the model to be fully capable at imputing the missing data.

<div><div><div><p>Impacting individual’s social and physical well-being, psychiatric disorders have been a substantial burden on public health. As such disorders are frequently observed aggregating in families, we can expect a large involvement of heritable components underlying their etiologies. Therefore, studying the genetic architecture and basis is one of the most important aims toward developing effective treatments for psychiatric disorders. The overall objective of this dissertation is to contribute to understanding the genetics of psychiatric disorders. Analyzing summary statistics from genomewide association studies (GWAS) of psychiatric disorders, we mainly present results of two projects. In the first one, we evaluated commonalities and distinctions in genetic risk of four highly comorbid childhood onset neuropsychiatric disorders: attention deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), obsessive-compulsive disorder (OCD) and Tourette’s syndrome (TS). Through systematic analysis of genetic architecture and correlation, we confirmed exitance of genetic components shared across ADHD, ASD and TS, as well as OCD and TS. Subsequently, we identified those components at variant, gene, and tissue specificity levels through meta-analyses. Our results pointed toward possible involvement of hypothalamus-pituitary-adrenal (HPA) axis, a human stress response system, in the etiology of these childhood onset disorders. The second project includes the proposition of a novel framework for general GWAS summary statistics-based analyses. Instead of regular odds ratio and standard errors archived in the summary statistics, we proposed a recounstruction approach to rewrite the results in terms of single nucleotide polymorphisms (SNP) allelic and genotypic frequencies. We also put forward three applications built-upon the proposed framework, and evaluated the performance on both synthetic data and real GWAS results of psychiatric disorders for each of them. Through these three applications, we demonstrated that this framework can broaden the scope of GWAS summary statistics-based analyses and unify various of analyses pipelines. We hope our work can serve as a stepping-stone for future researchers aiming at understanding and utilizing GWAS results of complex psychiatric disorders.</p></div></div></div>