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Waldron, Edward. "Analysis of genetic association studies via haplotype clustering." Thesis, Imperial College London, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.497253.
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Tai, Bik-wah Diana, and 戴碧華. "Haplotype analysis of the family with Lynch syndrome." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2010. http://hub.hku.hk/bib/B45153772.
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Yatskiv, Yuriy Romanovich. "A Haplotype Analysis of an Archaic Denisovan Genome." University of Toledo Health Science Campus / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=mco1481145733356233.
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Zhao, Jiantao. "Combining Association and Haplotype Studies Towards the Improvement of Fruit Quality in Tomato Multiple haplotype-based analyses provide genetic and evolutionary insights into tomato fruit weight and composition Meta-analysis of genome-wide association studies provides insights into genetic control of tomato flavor Genomic designing for climate smart tomato." Thesis, Avignon, 2019. http://www.theses.fr/2019AVIG0712.
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Les consommateurs se plaignent de la qualité gustative des tomates depuis des décennies. Celle-ci est influencée principalement par les sucres, les acides et un ensemble de divers composés volatils. L’amélioration de la saveur de la tomate reste l’un des principaux défis à relever pour améliorer la qualité de la tomate et l’acceptabilité des consommateurs pour l’amélioration moderne des tomates. Le but principal de cette thèse était de disséquer le contrôle génétique de la saveur de la tomate en utilisant des SNP à haute densité et un ensemble divers de traits liés à la saveur, notamment les sucres, les acides, les acides aminés et les composés volatils. Dans la première partie, j'ai effectué plusieurs analyses basées sur l’exploration des haplotypes dans une collection d’accessions. Plusieurs approches ont été utilisées et comparées pour identifier les régions génomiques en cours de sélection. Les modèles bayésiens de génétique d’association basés sur les haplotypes et une partie des SNP ont identifié 108 associations significatives pour 26 caractères. Parmi ces associations, certains gènes candidats prometteurs ont été identifiés. Certains avantages de l’utilisation des haplotypes ont également été présentés. Dans la deuxième partie, j'ai réalisé une méta-analyse d'études d'association pangénomique à l'aide de trois panels d'associations de tomates. J'ai démontré l'efficacité de l'imputation des génotypes pour augmenter la couverture de SNP à l'échelle du génome. Des méta-analyses de modèles à effets fixes et à effets aléatoires (pour les SNP présentant une hétérogénéité I2 > 25) ont été effectuées afin de contrôler l'hétérogénéité croisée des études. Au total, 305 locus significatifs ont été identifiés, dont 211 nouveaux. Parmi ceux-ci, 24 locus ont présenté des cis-eQTL lors d'une précédente étude d'association à l'échelle du transcriptome de fruits. L'analyse d'enrichissement pour toutes les associations a montré que jusqu'à 10 processus biologiques étaient enrichis de manière significative et que tous étaient étroitement impliqués dans les métabolites liés aux arômes. Une liste de gènes candidats prometteurs a été fournie, qui pourraient présenter un grand intérêt pour la validation fonctionnelle. J'ai également démontré la possibilité d'augmenter de manière significative le contenu en composés volatils qui contribuent de manière positive aux préférences des consommateurs tout en réduisant les volatils désagréables, en sélectionnant les combinaisons d'allèles pertinentes. Globalement, cette thèse augmente les connaissances du contrôle génétique du goût de la tomate, ce qui devrait contribuer à son amélioration<br>Consumers have been complaining about tomato flavor for decades. Tomato taste is mainly influenced by sugars, acids and a diverse set of volatiles. Improving tomato flavor remains one of the main challenges for improving tomato sensory quality and consumer acceptability in modern tomato breeding. The main purpose of this thesis was to decipher the genetic and evolutionary control of tomato flavor by using high density SNPs and a diverse set of flavor-related metabolites, including sugars, acids, amino acids and volatiles. In the first part, I performed multiple haplotype-based analyses on a tomato core collection. Several approaches were used and compared to identify the genomic regions under selection. Haplotype and SNP-based Bayesian models identified 108 significant associations for 26 traits. Among these associations, some promising candidate genes were identified. I also compared marker local haplotype sharing (mLHS) with LD in determining the candidate regions. In addition, some general benefits of using haplotypes were also provided as general discussions. In the second part, I pioneered in introducing meta-analysis of genome-wide association studies using three tomato association panels. I demonstrated the efficiency of genotype imputation in increasing the genome-wide SNP coverage. Both fixed-effect and random-effect models (for those SNPs with heterogeneity I2 > 25) of meta-analysis were performed in order to control cross-study heterogeneity. A total of 305 significant loci were identified and 211 of which were new. Among them, 24 loci exhibited cis-eQTLs in a previous transcriptome-wide association study in fruit tissue. Enrichment analysis for all associations showed that up to 10 biological processes were significantly enriched and all of which were closely involved in flavor-related metabolites. A list of promising candidate genes was provided, which could be of great interest for functional validation. I also demonstrated the possibility to significantly increase the content of volatiles that positively contribute to consumer preferences while reducing unpleasant volatiles, by selection of the relevant allele combinations. Taken together, this thesis provides a comprehensive knowledge of the genetic control of tomato flavor, which will promote its improvement
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Lächelt, Sandra [Verfasser]. "Funktionelle Analyse von ABCC2-Haplotypen / Sandra Lächelt." Kiel : Universitätsbibliothek Kiel, 2009. http://d-nb.info/1019869933/34.
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Hughes, David J. "Mutation characterisation and microsatellite haplotype analysis of the CFTR gene." Thesis, Queen's University Belfast, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.361278.
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Osman, Abdimajid. "Studies on warfarin treatment with emphasis on inter-individual variations and drug monitoring." Doctoral thesis, Linköping : Linköping University, 2007. http://www.bibl.liu.se/liupubl/disp/disp2007/med1000s.pdf.
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ROSA, Rogério dos Santos. "Associating genotype sequence properties to haplotype inference errors." Universidade Federal de Pernambuco, 2015. https://repositorio.ufpe.br/handle/123456789/16011.
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Previous issue date: 2015-03-12<br>Haplotype information has a central role in the understanding and diagnosis of certain
illnesses, and also for evolution studies. Since that type of information is hard to obtain directly,
computational methods to infer haplotype from genotype data have received great attention
from the computational biology community. Unfortunately, haplotype inference is a very hard
computational biology problem and the existing methods can only partially identify correct
solutions. I present neural network models that use different properties of the data to predict
when a method is more prone to make errors. I construct models for three different Haplotype
Inference approaches and I show that our models are accurate and statistically relevant. The
results of our experiments offer valuable insights on the performance of those methods, opening
opportunity for a combination of strategies or improvement of individual approaches. I formally
demonstrate that Linkage Disequilibrium (LD) and heterozygosity are very strong indicators
of Switch Error tendency for four methods studied, and I delineate scenarios based on LD
measures, that reveal a higher or smaller propension of the HI methods to present inference
errors, so the correlation between LD and the occurrence of errors varies among regions along
the genotypes. I present evidence that considering windows of length 10, immediately to the
left of a SNP (upstream region), and eliminating the non-informative SNPs through Fisher’s
Test leads to a more suitable correlation between LD and Inference Errors. I apply Multiple
Linear Regression to explore the relevance of several biologically meaningful properties of the
genotype sequences for the accuracy of the haplotype inference results, developing models for
two databases (considering only Humans) and using two error metrics. The accuracy of our
results and the stability of our proposed models are supported by statistical evidence.<br>Haplótipos têm um papel central na compreensão e diagnóstico de determinadas doenças
e também para estudos de evolução. Este tipo de informação é difícil de obter diretamente,
diante disto, métodos computacionais para inferir haplótipos a partir de dados genotípicos têm
recebido grande atenção da comunidade de biologia computacional. Infelizmente, a Inferência
de Halótipos é um problema difícil e os métodos existentes só podem predizer parcialmente
soluções corretas. Foram desenvolvidos modelos de redes neurais que utilizam diferentes
propriedades dos dados para prever quando um método é mais propenso a cometer erros. Foram
calibrados modelos para três abordagens de Inferência de Haplótipos diferentes e os resultados
validados estatisticamente. Os resultados dos experimentos oferecem informações valiosas sobre
o desempenho e comportamento desses métodos, gerando condições para o desenvolvimento
de estratégias de combinação de diferentes soluções ou melhoria das abordagens individuais.
Foi demonstrado que Desequilíbrio de Ligação (LD) e heterozigosidade são fortes indicadores
de tendência de erro, desta forma foram delineados cenários com base em medidas de LD, que
revelam quando um método tem maior ou menor propensão de cometer erros. Foi identificado
que utilizando janelas de 10 SNPs (polimorfismo de um único nucleotídeo), imediatamente a
montante, e eliminando os SNPs não informativos pelo Teste de Fisher leva-se a uma correlação
mais adequada entre LD e a ocorrência de erros. Por fim, foi aplicada análise de Regressão Linear
para explorar a relevância de várias propriedades biologicamente significativas das sequências de
genótipos para a precisão dos resultados de Inferência de Haplótipos, estimou-se modelos para
duas bases de dados (considerando apenas humanos) utilizando duas métricas de erro. A precisão
dos resultados e a estabilidade dos modelos propostos foram validadas por testes estatísticos.
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Nettelblad, Carl. "Two Optimization Problems in Genetics : Multi-dimensional QTL Analysis and Haplotype Inference." Doctoral thesis, Uppsala universitet, Avdelningen för beräkningsvetenskap, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-180920.
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The existence of new technologies, implemented in efficient platforms and workflows has made massive genotyping available to all fields of biology and medicine. Genetic analyses are no longer dominated by experimental work in laboratories, but rather the interpretation of the resulting data. When billions of data points representing thousands of individuals are available, efficient computational tools are required. The focus of this thesis is on developing models, methods and implementations for such tools. The first theme of the thesis is multi-dimensional scans for quantitative trait loci (QTL) in experimental crosses. By mating individuals from different lines, it is possible to gather data that can be used to pinpoint the genetic variation that influences specific traits to specific genome loci. However, it is natural to expect multiple genes influencing a single trait to interact. The thesis discusses model structure and model selection, giving new insight regarding under what conditions orthogonal models can be devised. The thesis also presents a new optimization method for efficiently and accurately locating QTL, and performing the permuted data searches needed for significance testing. This method has been implemented in a software package that can seamlessly perform the searches on grid computing infrastructures. The other theme in the thesis is the development of adapted optimization schemes for using hidden Markov models in tracing allele inheritance pathways, and specifically inferring haplotypes. The advances presented form the basis for more accurate and non-biased line origin probabilities in experimental crosses, especially multi-generational ones. We show that the new tools are able to reconstruct haplotypes and even genotypes in founder individuals and offspring alike, based on only unordered offspring genotypes. The tools can also handle larger populations than competing methods, resolving inheritance pathways and phase in much larger and more complex populations. Finally, the methods presented are also applicable to datasets where individual relationships are not known, which is frequently the case in human genetics studies. One immediate application for this would be improved accuracy for imputation of SNP markers within genome-wide association studies (GWAS).<br>eSSENCE
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Neville, Catherine E. "The high resolution haplotype analysis and origin of the myotonic dystrophy mutation." Thesis, University of Ottawa (Canada), 1994. http://hdl.handle.net/10393/9857.
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The objective of this thesis was to determine the origin of the myotonic dystrophy (DM) mutation. I have used PCR-based assays of nine polymorphisms spanning a physical distance of 30 kb, within and immediately flanking the DM kinase gene, in order to examine patterns of allelic association with respect to the DM mutation. Four main haplotypes (A-D) were observed in the normal population using these nine markers at the DM locus. Significantly, DM is in complete association with haplotype A, the most common haplotype in the normal population. Our data suggest the presence of two founding chromosomes: one containing a stretch of five contiguous Alu elements (the progenitor for haplotype A) and the other in which three of these have been deleted (the progenitor for haplotypes B, C and D). Individuals with haplotype A displayed the full spectrum of (CTG)$\sb{\rm n}$ number, ranging from 5 to 35 repeats. The (CTG)$\sb5$ alleles as well as alleles with greater than 19 repeats are exclusively linked to haplotype A. In contrast, alleles in which the three Alu elements are deleted possess only (CTG)$\sb{11-14}$ repeats. Although the inference that the loss of the three Alu repeats may confer increased stability on the (CTG)$\sb{\rm n}$ repeat is speculative, the narrow size range of the (CTG)$\sb{\rm n}$ repeat on chromosomes in which the Alu elements have been deleted, relative to the variation seen on normal chromosomes with the DM haplotype (i.e. haplotype A), is striking. (Abstract shortened by UMI.)
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Dennis, Gary Jon. "A haplotype analysis of the angiotensin converting enzyme gene in ischaemic stroke." Thesis, University of Leicester, 2008. http://hdl.handle.net/2381/8737.
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Background: Epidemiological studies lend some support for a genetic predisposition to human stroke. There is a growing body of evidence to suggest a role for Angiotensin II (ANGII) in vascular disease. The levels of Angiotensin converting enzyme (ACE), which converts ANGI to ANGII, are known to be under a significant degree of genetic control. The D allele of the ACE I/D polymorphism is associated with higher serum ACE levels and this allele has also been associated with ischaemic stroke. Recent identification of numerous ACE single nucleotide polymorphisms has allowed for a more powerful case control haplotype analysis of ACE in ischaemic stroke. Patients and Methods: The validity of the published structure of the common ACE haplotypes was investigated and supported using long range allele specific PCR and DNA sequencing of a random sample of UK caucasian subjects. Using restriction fragment length polymorphism (RFLP) analysis of selected polymorphisms we generated ACE haplotypes for 359 ischaemic stroke patients and 328 unrelated controls. Results: Age, hypertension, smoking, diabetes and hypercholesterolaemia were identified as significant clinical risk factors for ischaemic stroke. D allele frequencies showed no significant differences between cases and controls (0.55 vs 0.53 respectively). However a low frequency D allele haplotype (H9) was found to be an independent risk factor for ischaemic stroke (odds ratio 2.05, p=0.004). Conclusion: This study has provided allele specific data to support the haplotype structure of the common ACE haplotypes in a UK caucasian population. For the first time, in a case control analysis, we have identified a significant and independent genetic association of a low frequency ACE haplotype, H9, with human ischaemic stroke. This result suggests an important role for ACE in ischaemic stroke which will require further study in other populations using a variety of control groups.
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Belbin, Olivia. "Haplotype analysis of candidate genes in the amyloid cascade of Alzheimer's disease." Thesis, University of Nottingham, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.519432.
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Schouten, Michael T. "Modelling dependencies in genetic-marker data and its application to haplotype analysis." Thesis, University of Edinburgh, 2008. http://hdl.handle.net/1842/30729.
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The objective of this thesis is to develop new methods to reconstruct haplotypes from phase-unknown genotypes. The need for new methodologies is motivated by the increasing availability of high-resolution marker data for many species. Such markers typically exhibit Linkage Disequilibrium (LD). It is believed that reconstructed haplotypes for markers in high LD can be valuable for a variety of application areas in population genetics, including reconstructing population history and identifying genetic disease variants. The thesis begins with a critical assessment of the limitations of existing methods, and then presents a unified statistical framework that can accommodate pedigree data, unrelated individuals and tightly linked markers. The framework makes use of graphical models, where inference entails representing the relevant joint probability distribution as a graph and the using associated algorithms to facilitate computation. The graphical model formalism provides invaluable tools to facilitate model specification, visualization, and inference. Once the unified framework is developed, a broad range of simulation studies are conducted using previously published haplotype data. Important contributions include demonstrating the different ways in which the haplotype frequency distribution can impact the accuracy of both the phase assignments and haplotype frequency estimates; evaluating the effectiveness of using family data to improve accuracy for different frequency profiles; and, assessing the dangers of treating related individuals as unrelated in an association study.
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Kamihara-Ting, Junne. "Studies at the hemochromatosis (HFE) locus : gene conversions, haplotypes, and association analysis." Thesis, Massachusetts Institute of Technology, 2005. http://hdl.handle.net/1721.1/34193.
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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, February 2006.<br>Includes bibliographical references.<br>Haplotype-based association studies offer an exciting potential methodology for the identification of genes that contribute to complex traits. There is thus great interest in understanding the biological forces that shape haplotypes. We have studied a well-characterized genetic locus surrounding the gene responsible for hereditary hemochromatosis (HFE) to investigate the impact of meiotic recombination events upon haplotype structure in this region. First we identified crossover hotspots in order to define the boundaries of haplotype blocks in this locus. We then found that gene conversion events play a significant role in shaping haplotype structure within these haplotype blocks. These gene conversion events were not limited to recombination hotspots and occurred with a frequency as high as 1 in 104 per site per generation. Gene conversions lead to the creation of new haplotypes and we suggest that they are important for the spread of disease alleles in a population. In addition, we discuss how these events can be used as important tools in haplotype-based association studies. We also present an association study in a large Venezuelan cohort to search for genes that contribute to residual age of onset in Huntington's disease. We demonstrate significant association between multiple alleles in a region on chromosome 6p21.3.<br>(cont.) We identify two candidate genes in this region, HFE and histone Hlt and demonstrate significant association of this region with age of onset in a male-specific model.<br>by Junne Kamihara-Ting.<br>Ph.D.
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Floyd, James A. B. "Analysis of high-density SNP data from complex populations." Thesis, University of Edinburgh, 2011. http://hdl.handle.net/1842/4926.
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Data from a Croatian isolate population are analysed in a genome-wide association study (GWAS) for a variety of disease-related quantitative traits. A novel genomewide approach to analysing pedigree-based association data called GRAMMAR is utilised. One of the significant findings, for uric acid, is followed up in greater detail, and is replicated in another isolate population, from Orkney. The associated SNPs are located in the SLC2A9 gene, coding for a known glucose transporter, which leads to identification of SLC2A9 as a urate transporter too (Vitart et al., 2008). These SNPs are later implicated in affecting gout, a disease known to be linked with high serum uric acid levels, in an independent study (Dehghan et al., 2008). Subsequently, investigation into different ways in which to use SNP data to identify quantitative trait loci (QTL) for genome-wide association (GWA) studies is performed. Several multi-marker approaches are compared to single SNP analysis using simulated phenotypes and real genotype data, and results show that for rare variants haplotype analysis is the most effective method of detection. Finally, the multi-marker methods are compared with single SNP analysis on the real uric acid data. Interpretation of real data results was complicated due to low sample size, since only founder and unrelated individuals may be used for population-based haplotype analysis, nonetheless, results of the prior analyses of simulated data indicate that multi-marker methods, in particular haplotypes, may greatly facilitate detection of QTL with low minor allele frequency in GWA studies.
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Lee, Seung-Hwan. "From Cmv1 to Ly49h: Molecular genetics, haplotype analysis and transgenesis to characterize innate immunity to cytomegalovirus." Thesis, University of Ottawa (Canada), 2004. http://hdl.handle.net/10393/29133.
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In mice, natural resistance to infection with murine cytomegalovirus (MCMV) is controlled by a dominant chromosome 6 locus, Cmv1, which is expressed at the level of Natural killer (NK) cells. To characterize the molecular mechanism underlying MCMV-resistance, our laboratory initiated a positional cloning approach for the identification of Cmv1, and localized the host resistance locus to a 0.35 cM genetic interval, corresponding to 1.6 Mb genomic DNA.
This dissertation presents the results leading to the cloning and characterization of the Cmv1 gene. First, I constructed a transcription map for the Cmv1 interval, which included 19 genes comprising the full Ly49 gene cluster and other novel candidate genes. In an attempt to narrow down the localization of Cmv1, I determined haplotypes in the vicinity of the Cmv1 interval in a panel of 17 inbred mice strains. This approach demonstrated the presence of three major classes of independent haplotypes. Close inspection of allele sharing among those haplotypes excluded Ly49e, Ly49f and Ly49d as Cmv1 candidates.
As an alternative approach to cloning Cmv1, I took advantage of a recombinant inbred strain, the BXD-8 strain. The BXD-8 line was of particular interest because it is susceptible to MCMV infection while harboring an MCMV-resistance C57BL/6 haplotype at Cmv1. Using STS content and PFGE analysis, I showed the presence of a 23 kb deletion in BXD-8. Subsequent gene expression analysis of the full Ly49 gene cluster revealed that the deletion of Ly49h is associated with MCMV susceptibility in BXD-8 mice.
Finally, to test the role of Ly49h in host resistance to MCMV infection, I introduced the Ly49h gene into a susceptible background. Investigation of Ly49h gene expression by RT-PCR and FRCS analysis demonstrated a strong correlation between the level of Ly49h mRNA and protein expression and the control of MCMV replication, providing conclusive evidence of the allelism between Cmv1 and Ly49h.
In conclusion, I identified the Ly49h gene encoding a NK activation receptor as Cmv1 supporting a specific role for NK cells in antiviral immunity. Transgenic mice expressing Ly49H will be instrumental for understanding of mechanism of NK mediated resistance and possible pleiotropic effects of Cmv1.
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Zaboli, Ghazal. "Genes of the serotonergic system & susceptibility to psychiatric disorders : a gene-based haplotype analysis approach /." Stockholm, 2006. http://diss.kib.ki.se/2006/91-7140-729-4/.
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Coulonges, Cédric. "Analyses bioinformatiques dans le cadre de la génomique du SIDA." Phd thesis, Conservatoire national des arts et metiers - CNAM, 2011. http://tel.archives-ouvertes.fr/tel-00682191.
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Les technologies actuelles permettent d'explorer le génome entier pour y découvrir des variants génétiques associés aux maladies. Cela implique des outils bioinformatiques adaptés à l'interface de l'informatique, des statistiques et de la biologie. Ma thèse a porté sur l'exploitation bioinformatique des données génomiques issues de la cohorte GRIV du SIDA et du projet international IHAC (International HIV Acquisition Consortium). Posant les prémices de l'imputation, j'ai d'abord développé le logiciel SUBHAP. Notre équipe a montré que la région HLA était essentielle dans la non progression et le contrôle de la charge virale et cela m'a conduit à étudier le phénotype non-progresseur non " elite ". J'ai ainsi révélé un variant du gène CXCR6 qui, en dehors du HLA, est le seul résultat identifié par approche génome-entier et répliqué. L'imputation des données du projet IHAC (10000 patients infectés et 15000 contrôles) a été réalisée et des premières associations sont en cours d'exploration.
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Bochernitsan, Aline Nemetz. "Mucopolissacaridose IVA : análise molecular e caracterização de haplótipos intragênicos no gene Galns." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2015. http://hdl.handle.net/10183/139801.
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Introdução: Mucopolissacaridose IVA é uma doença lisossômica, autossômica recessiva, causada pela deficiência da enzima N-acetilgalactosamina-6-sulfatase. É uma doença rara e a incidência varia de 1:76.000 a 1:640.000 recém-nascidos vivos. Até o momento 319 diferentes mutações causadoras da doença já foram identificadas, o que demonstra a ampla variabilidade genética. Objetivo: Caracterizar o genótipo de pacientes com MPS IVA, analisar 6 polimorfismos intragênicos e identificar os haplótipos presentes em nossos pacientes, através do estudo molecular do gene GALNS. Métodos: O estudo foi realizado em 45 pacientes provenientes das regiões Nordeste, Sudeste, e Sul do Brasil, com diagnóstico bioquímico confirmado para MPS IVA. A análise molecular foi realizada através de PCR seguida de sequenciamento, pelo método de Sanger, a fim de identificar as mutações causadoras da doença. Para o estudo de haplótipos foram analisados 6 polimorfismos intragênicos através de PCR em Tempo Real, pelo método Taqman, em pacientes e controles. Resultados: A análise do gene GALNS, nos 45 pacientes, permitiu a identificação de 18 diferentes mutações, e a caracterização de 6 haplótipos distintos. Das 18 mutações encontradas, 5 apresentaram uma alta frequência (p.Ser341Arg, p.Arg386Cys, p.Gly301Cys, p.Arg94Leu e p.Gly116Ser), além disso, foram encontradas 4 novas mutações em outros três pacientes (p.Gly115Arg, p.Asn45Gly, p.Thr394Ala e c.759-2A>G). Dentre as mutações encontradas com maior frequência, a mutação p.Ser341Arg foi identificada em um maior número de pacientes, sendo a maioria proveniente da região Nordeste. Além disso, todos os pacientes com esta mutação apresentaram um único haplótipo. Conclusão: Os resultados obtidos permitiram a identificação de 18 mutações dentre elas 4 novas mutações. A alta frequência da mutação p.Ser341Arg no Nordeste do Brasil, principalmente no estado da Paraíba nos leva a inferir um possível efeito fundador da doença. Esta mutação foi observada somente na população brasileira e todos os pacientes com mutação em homozigose apresentaramum único haplótipo. Estas análises são importantes para identificar portadores nas famílias, para diagnóstico pré-natal, e também como forma de identificar uma origem comum em mutações frequentes em determinadas populações.<br>Background: Mucopolysaccharidosis IVA is an autosomal recessive lysosomal disease, caused by deficiency of N-acetilgalactosamina-6-sulfatase. It is a rare disease and the incidence ranges from 1: 76,000 to 1:640,000 live births. To date 319 mutations have been identified in this gene, demonstrating the wide variability of disease causing mutations. Objective: Analyze and characterize the genotype of patients with MPS IVA, through molecular analysis of GALNS. Methods: Molecular analysis of 45 patients with confirmed biochemical diagnosis for MPS IVA was performed. Mutation analysis was performed by PCR followed by Sanger sequencing. Haplotype analysis was performed using 6 intragenic polymorphisms by Real-Time PCR. Results: In this study we found 18 different mutations among 45 Brazilian patients and identified 5 common mutations (p.Ser341Arg, p.Arg386Cys, p.Gly301Cys, p.Arg94Leu e p.Gly116Ser). Four novel mutations were also identified through molecular analysis, including: p.Gly115Arg, p.Asn45Gly, p.Thr394Ala e c.759-2A>G. Patients are distributed in Northeast, Southeast and South regions of Brazil. Six different haplotypes were identified among patients. The p.Ser341Arg mutation showed the highest frequency, and most patients are located in the Northeast, additionally, all patients with this mutation show the same haplotype.Conclusion: These analyzes are important to identify carriers in families, for prenatal diagnosis, and in order to identify the mutation origin when certain recurrent mutation is associated with the same haplotype. In this study, we observed a high frequency of p.Ser341Arg mutation in Northeast, mainly in the state of Paraíba. This mutation was detected with higher frequency among patients, and showed only a haplotype. This mutation is unique for the Brazilian population and thus, we could suggest that a possible founder effect for this mutation could exist.
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Ferreira, Irma. "Haplotipe-analise van die fenielalanienhidroksilase-lokus in families met fenielketonurie / Irma Mohr." Thesis, Potchefstroom University for Christian Higher Education, 1989. http://hdl.handle.net/10394/7421.
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Cloning of a full-length human cDNA for phenylalanine hydroxylase (PAH) has led to major advances In the application of recombinant DNA techniques to the study of classical phenylketonuria (PKU) I a common autosomal recessive inborn error of amino acid metabolism (Ledley et al, 1985b). In order to assess the possible application of RFLP analysis for the identification of carriers of the trait among South African Caucasians, the frequencies of eight restriction site polymorphisms in a panel of random Caucasians were determined using a human PAH cDNA clone (obtained from S. L. C. Woo). The frequencies of the minor alleles exceed 0,12 for all of the restriction endonukleases, confirming the existence of a very high degree of polymorphism at the human PAH locus. Moreover, in the panel of random Caucasian individuals, 35 out of 36 are RFLP heterozygotes, which yielded an observed heterozygosity of 97%. The data, therefore, suggest that a large percentage of South African Caucasian PKU families may be successfully analysed with RFLP haplotype analysis. In all of the families thus far studied digestion by a battery of eight selected restriction endonucleases yielded RFLP patterns which were informative for either the detection of homozygotes for the defective PAH alleles or the identification of carriers of the PKU trait. Of particular interest is the finding that none of the observed eight haplotypes associated with defective PAH alleles show a predominant distribution. This may indicate that the various PKU alleles do not have a common origin, or that the PAH gene is especially prone to recombination events. In fact, we have observed a meiotic crossing-over event between two PAH alleles in a large family.
Various facets of my work have been presented at international and local scientific meetings.<br>Thesis (MSc)--PU vir CHO, 1989.
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PIROLA, YURI. "Combinatorial problems in studies of genetic variations: haplotyping and transcript analysis." Doctoral thesis, Università degli Studi di Milano-Bicocca, 2010. http://hdl.handle.net/10281/7891.
Full textAbstract:
After the first draft of the human genome has been published, the study of genetic variations has attracted increasing attention as a medium to map observable characteristics (phenotypic traits) of individuals to their underlying genes and biological processes. Unfortunately, observing and obtaining directly the genetic data of interest is a long and expensive operation, especially for large populations. Less informative sources of data are instead available at a fraction of cost. Computational methods are then called to recover the original data of interest from their less informative observations.
The design of efficient combinatorial algorithms to infer relevant data for genetic variation studies starting from less informative observations is the main aim of the work of this thesis. In particular, we focused on two different kinds of data of crucial importance for genetic variation studies: haplotypes and transcripts.
In the first part of the thesis, we studied the Haplotype Inference (HI) problem that requires to infer, for each individual of a population, the genetic sequences inherited from each parent (haplotypes) starting from their conflation (genotype). We formulated and analyzed two different computational problems of haplotype inference: the pure parsimony xor-haplotyping problem (PPXH) and the minimum event haplotype configuration problem (MinEHC). In the first problem, the haplotype inference process is guided by the pure parsimony criterion and it starts from a recently proposed representation of genotypes, called xor-genotypes. For this problem, we presented exact and approximate solutions by providing (i) polynomial time exact algorithms for some restricted cases, (ii) a fixed-parameter algorithm for the general case, and (iii) a polynomial time k-approximation algorithm, where k is the maximum number of heterozygous individuals at a given marker locus. These results are based on some interesting combinatorial properties of a graph representation of the solutions. Furthermore, we proposed a heuristic algorithm that can scale to real-world large instances, as shown in an extensive experimental evaluation. In the second HI problem, we assumed that parental relationships among members of the population are known. In the thesis we formulated and studied the HI problem on such populations under the assumption that the two most frequent kinds of variation events, namely recombinations and mutations, can occur. This formulation significantly extends previous works where only one of them (or none) was allowed. We proved that the problem, called MinEHC, is computationally hard to solve or to approximate even on simple instances. However, we provided a heuristic algorithm that has shown extremely good performances, both in terms of accuracy and running times, on several simulated scenarios. The heuristic algorithm is based on a L-reduction from MinEHC to a well-known coding problem, Decoding of Linear Codes (DLC). By (heuristically) solving DLC, we are able to recover the set of genetic variations that have occurred in the population and, then, to infer the set of haplotypes.
In the second part of the thesis, we analyzed the problem of predicting the gene structure by aligning transcript fragments to a reference genomic sequence. Traditional basic approaches focus on computing high-quality transcript alignments that should reveal the gene structure. However, inherent ambiguities in the transcript alignments could heavily affect the prediction quality. In the thesis, instead, we formulated the gene structure prediction problem as the problem of choosing the simplest gene structure that can “explain” ambiguous alignments of several transcript fragments. We proposed two fast algorithmic solutions for the two combinatorial problems that stem from such formulation. The first algorithm efficiently computes all the possible (and biologically meaningful) alignments of a given transcript against a reference genomic sequence. The second algorithm, given all the possible alignments of a set of transcripts, extracts a single factorization for each transcript such that the induced gene structure is composed by the minimum number of expressed regions (exons). We also conducted an experimental evaluation of our strategy on a significant set of genes, and promising preliminary results have emerged even in absence of specific biological criteria.
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Menard, Katrina Louise. "Population genetic structure of Conophthorus ponderosae Hopkins (Coleoptera: Scolytidae) inferred from mitochondrial DNA haplotypes." Texas A&M University, 2006. http://hdl.handle.net/1969.1/4210.
Full textAbstract:
Pine cone beetles (Conophthorus sp.) are serious pests of many forest ecosystems
since they burrow into pine cone tissues for egg deposition, causing the death of the
seeds. Management of these beetles in natural and commercial stands of pines has been
problematic due to lack of understanding about species limits and distribution. This study
was conducted to investigate the phylogeography and phylogenetics of the genus. Several
species represented by disjunct populations appear to be monophyletic including
Conophthorus edulis, C. mexicanus, C. coniperda, and C. conicollens, whereas C.
ponderosae is polyphyletic with many distinct clades isolated by geography. This study
explored whether host use or geography has played a greater role in the diversification of
this genus, focusing on the polyphyletic C. ponderosae and the monophyletic C. edulis.
In the first study, 751bp of the mtDNA CO1 gene were sequenced to reconstruct a
phylogeny of the genus, and the distribution and host use were compared to investigate
whether these factors were significantly associated. The second study addressed
population structure and possible historical influences on the C. edulis and C. ponderosae
populations using a nested clade analysis of the mtDNA haplotypes. Despite potential
limitations due to sampling, several conclusions could be drawn. Three separate
haplotype networks were found for the C. ponderosae haplotypes, indicating that there have been at least three lineages that have associated with P. ponderosa. Geography was
significantly associated with the phylogeny at greater distances (>900km), but host use
was not significant. At the species level, association with geography is variable.
Population structure for C. ponderosae at the species level is minimal, and suggests that
there has not been much time for lineage sorting of the haplotypes based on the nested
clade analysis as compared to C. edulis.
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Wilson, Lyle. "Genetic analysis of the Cape Sand Frog, Tomopterna delalandii (Tschudi 1838)." University of the Western Cape, 2015. http://hdl.handle.net/11394/4866.
Full textAbstract:
Magister Scientiae (Biodiversity and Conservation Biology) - MSc (Biodiv and Cons Biol)<br>Tomopterna delalandii occurs throughout the west coast, Western Cape and south coast of South Africa. This range stretches across three distinct biogeographical assemblages. Based on historical records and the fact that Tomopterna is a genus of cryptic frogs, it is possible that there are unknown genetic variations within the species. To investigate whether population structure is present within T. delalandii a mitochondrial gene and nuclear gene, 16S and Tyrosinase, was sequenced from across the range. Haplotype networks and cladograms were constructed to look
at the relationship between the genetic samples. This revealed definite population structuring between samples from the western edge of the range and samples from the eastern edge of the range. It also revealed that samples taken from the northern edge of the range, while matching general T. delalandii tadpole morphology, are genetically different. Further study needs to be made into the identity of this new form. This study shows that by using both mitochondrial and
nuclear DNA patterns can be discovered about the genetic structure of a species as well as revealing a new one.
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Serao, Nick, Dianelys Gonzalez-Pena, Jonathan Beever, Dan Faulkner, Bruce Southey, and Sandra Rodriguez-Zas. "Single nucleotide polymorphisms and haplotypes associated with feed efficiency in beef cattle." BioMed Central, 2013. http://hdl.handle.net/10150/610391.
Full textAbstract:
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<br>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.
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Genêt, Carine. "Caractérisation et analyse de régions du génome porcin portant des QTL de croissance, d'engraissement et de teneur en androsténone du gras." Montpellier 2, 2001. http://www.theses.fr/2001MON20060.
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RAVEANE, ALESSANDRO. "Human genetic history 2.0: Y-chromosome NGS in South American populations Genome-wide haplotype analysis in Italian populations." Doctoral thesis, Università degli studi di Pavia, 2018. http://hdl.handle.net/11571/1220606.
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Alburaki, Mohamed. "Analyse de la diversité moléculaire et morphométrique des populations d'abeilles de Syrie Apis mellifera syriaca : application à la conservation et à la sélection des populations d'abeilles." Paris 6, 2011. http://www.theses.fr/2011PA066199.
Full textAbstract:
Pour étudier la diversité génétique et morphométrique des populations d'abeille syrienne Apis mellifera syriaca, nous avons réalisé un échantillonnage de 1800 colonies d'abeilles couvrant trois pays différents: la Syrie, le Liban et l'Irak. Une abeille par colonie a été échantillonnée et conservée individuellement dans de l'alcool absolu. Ces abeilles ont été disséquées et les ailes conservées pour d'éventuelles analyses morphométriques. L'extraction des ADN totaux a été effectuée sur les thorax de ces abeilles. Chaque échantillon a ensuite été analysé pour deux marqueurs moléculaires: i) l'ADN mitochondrial, ii) 14 Loci microsatellites. Concernant le premier marqueur moléculaire, une CAPS (Cleaved Amplified Polymorphisms) a été effectuée dans la région intergénique non codante située entre les sous unités I et II du gène de la Cytochrome Oxydase (COI-COII). Cette analyse a permis l'identification de 18 nouveaux haplotypes spécifiques de l’abeille syrienne Apis mellifera syriaca inconnus auparavant et qui forment un sous groupe (nommé Z) de la lignée évolutive africaine (A). Ces haplotypes Z qui appartiennent à la lignée africaine et non pas à la lignée orientale comme cela a été décrit dans des études précédentes ont été ultérieurement séquencés et soumis à GenBank sous les numéros d'accès suivants: HM236202 - HM236219. D’autre part, les résultats moléculaires des populations d’abeilles de Syrie ont identifié, dans plusieurs régions syriennes, des importations d’abeilles étrangères comme mellifera, ligustica et carnica. Les populations d’abeilles de Syrie se trouvent dans une zone géographique influencée par deux lignées évolutives: la lignée orientale (O) au Nord et la lignée africaine (A) au Sud. La Syrie est située dans une zone d’introgression naturelle entre ces deux lignées expliquant l’incohérence des résultats trouvés dans la littérature. Cette influence se traduit par une forte introgression allélique de la lignée orientale dans les populations syriennes du Nord tandis que les populations du Sud, caractérisées par les haplotypes Z, appartiennent majoritairement à la lignée africaine (A). L’approche de la morphométrie géométrique confirme clairement les résultats moléculaires obtenus dans cette étude et s’avère une approche prometteuse pour la caractérisation des sous-espèces d’abeilles mellifères
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Russell, Kadijah Lashunte. "DNA Sequence and Haplotype Variation Analysis of Inflammatory Response Genes NLRX1, IL6, and IL8 in the Turkey (Meleagris gallopavo)." Thesis, Virginia Tech, 2019. http://hdl.handle.net/10919/99468.
Full textAbstract:
Genotype-phenotype analyses continue to be the primary goal for genome analyses in livestock and poultry breeding. Essential to accomplish this goal is the need to identify variation at the genomic level. To test the hypothesis that DNA sequence variations in inflammatory response genes are associated with phenotypic differences in the heritage turkey, the primary objective of this project was to search for single nucleotide polymorphisms (SNPs) in candidate inflammatory response genes. A minor objective was to develop a system for inducing inflammatory response in the turkey using a microbe-based lipopolysaccharide (LPS), an approach previously described for the chicken. A total of 18 SNPs was identified in the three genes screened in this project: Interleukin 6 (IL6) and 8 (IL8), and NLRX1. Mortality data from the LPS challenge were not significantly different among the strains. Further gene expression analyses will be part of future work. The SNP data represent the first extensive analyses of candidate inflammatory response genes in the turkey. Combined with the protocols developed for inflammation assessment in the turkey the SNPs described here will be valuable resources for future inflammation:genotype evaluation in the turkey
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Tell, Désirée von. "Welander distal myopathy : gene mapping and analysis of candidate genes /." Stockholm, 2004. http://diss.kib.ki.se/2003/91-7349-764-9.
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Su, Shu Yi. "Analysis of association studies and inference of haplotypic phase using hidden Markov models." Thesis, Imperial College London, 2009. http://hdl.handle.net/10044/1/5523.
Full textAbstract:
In this thesis I focus on the development and application of hidden Markov model (HMM) to solve problems in statistical genetics. Our method, based on a HMM, models the joint haplotype structure in the samples, where the parameters in the model are estimated by the Baum-Welch EM algorithm. Also, the model does not require pre-defined blocks or a sliding window scheme to define haplotype boundaries. Thus our method is computationally efficient and applicable for either the whole genome sequence or the candidate gene sequence. The first application of this model is for disease association testing using inferred ancestral haplotypes. We employed a HMM to cluster haplotypes into groups of predicted common ancestral haplotypes from diploid genotypes. The results from simulation studies show that our method greatly outperforms single-SNP analyses and has greater power than a haplotype-based method, CLADHC, in most simulation scenarios. The second application is for inferring haplotypic phase and to predict missing genotypes in polyploid organisms. Using a simulation study we demonstrate that the method provides accurate estimates of haplotypic phase and missing genotypes for diploids, triploids and tetraploids. The third application is for joint CNV/SNP haplotype and missing data inference. The results are very encouraging for this application. With the increasing availability of genotype data in both diploid and polyploid organisms, we believe that our programs can facilitate the investigation of genetic variations in genome-wide scale studies.
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Pountney, Angela. "Analysis of the population genetics and polybrominated diphenyl ether (PBDE) burdens of otters in England and Wales : with case studies of populations in South West England." Thesis, University of Exeter, 2008. http://hdl.handle.net/10036/110261.
Full textAbstract:
Otter populations declined drastically across many areas of England and Wales during the 1960s to 1980s. The main cause of this decline is thought to have been high concentrations of organic pollutants, in particular PCBs and dieldrin. Here we look at the health of the present day otter population, focussing on the numbers of otters, the genetic diversity of populations and investigating a possible new organic pollutant threat, polybrominated diphenyl ethers (PBDEs). A non-invasive spraint genotyping study of the otter population inhabiting the River Camel in Cornwall not only revealed that the river was capable of supporting a minimum number of 12 otters over a 9 month period, but gave insight into the ranges and genetic relationships of the individuals using the river system. A further population genetic study was carried out focussing on the River Itchen in Hampshire, a population which declined drastically to just a few isolated individuals before receiving otters through a captive breeding programme. Microsatellite genotyping of tissue samples showed the River Itchen population to be relatively diverse, indicating a successful population recovery, and haplotype analysis reveals that captive bred otters have successfully bred within the River Itchen population. However, haplotype analysis also indicates that the otters used to found the captive breeding programme were unlikely to have originated from a native British population. Concentrations of PBDEs in otters rival the high concentrations observed in many marine mammal species and are approaching the concentrations of PCBs and DDTs already observed in otters. The profile of the PBDE congeners found shows that lower congeners show relative concentrations similar to those observed in many other species of biota, with high BDE-47 dominating the profile and BDE-99 and -100 also found at significant concentrations. Otters also contain relatively high concentrations of the congeners BDE-153 and BDE-209, a trend generally typical of terrestrial top predators. In summary, the otter populations studied appear to be recovering well. However, increasing concentrations of PBDEs may cause problems for otter populations in the future.
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Zhao, Wanying. "Genetic, Age, and Spatial Structure to Improve Management of Common Privet (Ligustrum vulgare)." The Ohio State University, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=osu1325115045.
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CONGIU, RITA. "Analisi molecolare in pazienti italiani con sindrome di Lowe." Doctoral thesis, Università degli Studi di Cagliari, 2006. http://hdl.handle.net/11584/265881.
Full textAbstract:
The oculocerebrorenal syndrome of Lowe (OCRL, also called OCRL1) is a rare X-linked disorder characterized by major abnormalities of eyes, nervous system, and kidneys. The gene responsible for OCRL encodes an inositol polyphosphate-5-phosphatase. We performed the molecular analysis in 20 Italian patients and we detected the mutations in all the examined patients. Sixteen mutations out of twenty consisted of truncating mutations (frameshift, nonsense, splice site and genomic deletion), and four were missense mutations. The mutations were distributed in the second half of the gene as previously described in other populations. Our results on the Italian population are similar to the data previously obtained in other populations. Herein, we also report a family with extremely skewed X inactivation that produced the full phenotype of Lowe syndrome in a female. The X chromosome inactivation studies detected an extremely skewed inactivation pattern with a ratio of 100:0 in the propositus as well as in five out of seven unaffected female relatives in four generations. The OCRL1 "de novo" mutation resides in the active paternally inherited X chromosome. X chromosome haplotype analysis suggests the presence of a locus for the familial skewed X inactivation in chromosome Xq25 most likely controlling X chromosome choice in X inactivation or cell proliferation.
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Zhao, Zhiyu. "Robust and Efficient Algorithms for Protein 3-D Structure Alignment and Genome Sequence Comparison." ScholarWorks@UNO, 2008. http://scholarworks.uno.edu/td/851.
Full textAbstract:
Sequence analysis and structure analysis are two of the fundamental areas of bioinformatics research. This dissertation discusses, specifically, protein structure related problems including protein structure alignment and query, and genome sequence related problems including haplotype reconstruction and genome rearrangement. It first presents an algorithm for pairwise protein structure alignment that is tested with structures from the Protein Data Bank (PDB). In many cases it outperforms two other well-known algorithms, DaliLite and CE. The preliminary algorithm is a graph-theory based approach, which uses the concept of \stars" to reduce the complexity of clique-finding algorithms. The algorithm is then improved by introducing \double-center stars" in the graph and applying a self-learning strategy. The updated algorithm is tested with a much larger set of protein structures and shown to be an improvement in accuracy, especially in cases of weak similarity. A protein structure query algorithm is designed to search for similar structures in the PDB, using the improved alignment algorithm. It is compared with SSM and shows better performance with lower maximum and average Q-score for missing proteins. An interesting problem dealing with the calculation of the diameter of a 3-D sequence of points arose and its connection to the sublinear time computation is discussed. The diameter calculation of a 3-D sequence is approximated by a series of sublinear time deterministic, zero-error and bounded-error randomized algorithms and we have obtained a series of separations about the power of sublinear time computations. This dissertation also discusses two genome sequence related problems. A probabilistic model is proposed for reconstructing haplotypes from SNP matrices with incomplete and inconsistent errors. The experiments with simulated data show both high accuracy and speed, conforming to the theoretically provable e ciency and accuracy of the algorithm. Finally, a genome rearrangement problem is studied. The concept of non-breaking similarity is introduced. Approximating the exemplar non-breaking similarity to factor n1..f is proven to be NP-hard. Interestingly, for several practical cases, several polynomial time algorithms are presented.
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Hathaway, Nicholas J. "A suite of computational tools to interrogate sequence data with local haplotype analysis within complex Plasmodium infections and other microbial mixtures." eScholarship@UMMS, 2018. https://escholarship.umassmed.edu/gsbs_diss/970.
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The rapid development of DNA sequencing technologies has opened up new avenues of research, including the investigation of population structure within infectious diseases (both within patient and between populations). In order to take advantage of these advances in technologies and the generation of new types of data, novel bioinformatics tools are needed that won’t succumb to artifacts introduced by the data generation, and thus provide accurate and precise results. To achieve this goal I have create several tools.
First, SeekDeep, a pipeline for analyzing targeted amplicon sequencing datasets from various technologies, is able to achieve 1-base resolution even at low frequencies and read depths allowing for accurate comparison between samples and the detection of important SNPs. Next, PathWeaver, a local haplotype assembler designed for complex infections and highly variable genomic regions with poor reference mapping. PathWeaver is able to create highly accurate haplotypes without generating chimeric assemblies. PathWeaver was used on the key protein in pregnancy-associated malaria Plasmodium falciparum VAR2CSA which revealed population sub-structuring within the key binding domain of the protein observed to be present globally along with confirming copy number variation. Finally, the program Carmen is able to utilize PathWeaver to augment the results from targeted amplicon approaches by reporting where and when local haplotypes have been found previously.
These rigorously tested tools allow the analysis of local haplotype data from various technologies and approaches to provide accurate, precise and easily accessible results.
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Brinza, Dumitru. "Discrete Algorithms for Analysis of Genotype Data." Digital Archive @ GSU, 2007. http://digitalarchive.gsu.edu/cs_diss/19.
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Accessibility of high-throughput genotyping technology makes possible genome-wide association studies for common complex diseases. When dealing with common diseases, it is necessary to search and analyze multiple independent causes resulted from interactions of multiple genes scattered over the entire genome. The optimization formulations for searching disease-associated risk/resistant factors and predicting disease susceptibility for given case-control study have been introduced. Several discrete methods for disease association search exploiting greedy strategy and topological properties of case-control studies have been developed. New disease susceptibility prediction methods based on the developed search methods have been validated on datasets from case-control studies for several common diseases. Our experiments compare favorably the proposed algorithms with the existing association search and susceptibility prediction methods.
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MATTIOLI, CLAUDIA. "Association of HS1,2A polymorphism with several diseases and analysis of the haplotypes of the region surrounding the enhancer." Doctoral thesis, Università degli Studi di Roma "Tor Vergata", 2009. http://hdl.handle.net/2108/911.
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Nell’uomo due regioni regolative (3’RR-1 and 3’RR-2) situate a valle di ciascuno dei due geni alfa della regione costante della catena pesante delle immunoglobuline possiedono la capacità di stimolare l’attività dei promotori dei geni della catena pesante in una modalità tessuto-specifica e stadio-dipendente. Ciascuna regione regolativa umana possiede 3 elementi enhancer: HS3, HS1,2 and HS4. Fra questi, soltanto l’enhancer HS1,2 è risultato essere polimorfico. L’amplificazione selettiva dell’enhancer HS1,2A ha mostrato la presenza di 4 alleli (1; 2; 3; 4) aventi frequenze variabili nella popolazione mondiale. Uno degli scopi di questa tesi è studiare la distribuzione degli alleli dell’HS1,2A in Italia. La popolazione italiana è risultata essere piuttosto omogenea per questo locus. Nonostante ciò, le barriere naturali ostacolano i flussi genici fra la Sardegna ed il resto dell’Italia. Un effetto simile si riscontra nella regione “Sierra de Gredos” ed il resto della Spagna.
Studi precedenti hanno dimostrato l’associazione fra alcune patologie autoimmuni ed il polimorfismo dell’enhancer HS1,2A. Esperimenti di “gel shift” hanno inoltre mostrato che due diversi complessi proteici legano gli alleli 1 e 2 dell’HS1,2A. Questi dati suggeriscono un possibile ruolo del polimorfismo dell’HS1,2A nella regolazione delle funzioni dei linfociti B. In questa tesi lo studio viene esteso a varie patologie autoimmuni e alla sindrome da deficienza di IgA. I nostri risultati mostrano un aumento significativo della frequenza dell’allele 1 in un gruppo di pazienti affetti da deficienza di IgA rispetto al controllo. D’altra parte, la frequenza dell’allele 2 aumenta significativamente in individui affetti da varie patologie autoimmuni rispetto al controllo. Inoltre, l’allele 2 associa in modo più forte con la forma acuta di una data patologia rispetto a quella più lieve. L’associazione del polimorfismo dell’HS1,2A con l’alterazione dei livelli sierici delle immunoglobuline è stato inoltre studiato in questa tesi. L’aumento della frequenza dell’allele 1 associa significativamente con livelli sierici di immunoglobuline inferiori ai valori standard, mentre l’aumento della frequenza dell’allele 2 correla con livelli sierici di immunoglobuline superiori ai valori standard. È noto che i fattori genetici dell’ospite possono influenzare la progressione delle patologie virali. Studi precedenti hanno dimostrato la correlazione fra il polimorfismo dell’HS1,2A e la progressione dell’AIDS in un gruppo di pazienti libici. In questa tesi è stata trovata un’associazione del polimorfismo dell’HS1,2A con la diminuzione dei livelli dei linfociti CD4+ in un gruppo di individui HIV positivi provenienti dal Sud Africa. Abbiamo inoltre dimostrato che il polimorfismo dell’HS1,2A influenza la risposta individuale all’infezione del virus dell’Epatite C.
Successivamente, l’analisi è stata estesa alla regione situata fra gli enhancer HS3 ed HS1,2A della RR-1. In totale sono stati identificati 22 SNP in forte “linkage disequilibrium” l’uno con l’altro. Abbiamo trovato una correlazione significativa fra gli aplotipi e gli alleli dell’HS1,2A. Abbiamo ipotizzato che il polimorfismo dell’HS1,2A e gli aplotipi della regione regolativa “RR-1” possono influenzare i cambiamenti epigenetici o il legame di fattori di trascrizione alla regione regolativa, influenzando perciò l’attività della regione stessa nella trascrizione dei geni delle immunoglobuline, nello “switch” isotipico e nella produzione delle immunoglobuline.<br>In humans two regulatory regions (3’RR-1 and 3’RR-2) lying downstream of each of the two heavy chain constant alfa genes are able to enhance immunoglobulin transcription from the heavy chain promoters in a tissue-and-stage-specific manner. Each human regulatory region harbours three enhancer elements: HS3, HS1,2 and HS4. Among the enhancers, only HS1,2 proved to be polymorphic. The selective amplification of HS1,2A revealed the occurrence of four alleles (1; 2; 3; 4) which show variable frequencies throughout the world population. One aim of this thesis is to study the distribution of HS1,2A alleles in the Italian population. The Italian population turns out to be rather homogeneous for this locus. Nevertheless, natural barriers impair genetic flux in Sardinia in contrast to the homogeneity generally found in the rest of Italy. A similar effect is also found in Spain’s Sierra de Gredos region.
Previous studies have demonstrated the association of the HS1,2A polymorphism with some immunological diseases. Gel shift experiments have shown that two different protein complexes bind the HS1,2A alleles 1 and 2. These data suggest a role of the HS1,2A polymorphism in the regulation of B cell functions. In this thesis we extended the analysis to selective IgA deficiency and to several autoimmune diseases. We found a significant increase of allele 1 frequency in a group of patients affected by IgA deficiency in respect to the control. On the other hand, allele 2 frequency is significantly increased in individuals affected by different autoimmune diseases in respect to the control. Moreover, allele 2 associates strongly with the acute form of a given autoimmune disease in respect to the milder form. The association of HS1,2A polymorphism with the alteration of immunoglobulin serum levels was also investigated in this thesis. Allele 1 frequency increase associates significantly with immunoglobulin serum levels below the standard values, while allele 2 frequency increase correlates with immunoglobulin serum levels above the standard values. It is known that several host genetic factors influence the progression of viral pathologies. Previous studies have shown the correlation of HS1,2A polymorphism with AIDS progression in a cohort of Libyan patients. Here we found an association of HS1,2A polymorphism with the decrease of CD4+ T cell levels in a group of HIV positive subjects from South Africa. We also showed that the HS1,2A polymorphism could be involved in the individual response to Hepatitis C virus infection.
Subsequently, the analysis was extended to a region lying between the enhancers HS3 and HS1,2A of the 3’RR-1. In total, 22 single nucleotide polymorphisms in strong linkage disequilibrium with each other were identified. We found a strong significant correlation of the haplotypes with the HS1,2A alleles. We hypothesized that the HS1,2A polymorphism and the haplotypes of the 3’RR-1 could affect epigenetic changes or transcription factor binding to the regulative region, so influencing the regulative region activity in immunoglobulin germline transcription, in class switch recombination and in immunoglobulin production.
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Zhou, Xiaofei. "Bayesian Lasso for Detecting Rare Genetic Variants Associated with Common Diseases." The Ohio State University, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=osu1563455460578675.
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McCaskie, Pamela Ann. "Multiple-imputation approaches to haplotypic analysis of population-based data with applications to cardiovascular disease." University of Western Australia. School of Population Health, 2008. http://theses.library.uwa.edu.au/adt-WU2008.0160.
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[Truncated abstract] This thesis investigates novel methods for the genetic association analysis of haplotype data in samples of unrelated individuals, and applies these methods to the analysis of coronary heart disease and related phenotypes. Determining the inheritance pattern of genetic variants in studies of unrelated individuals can be problematic because family members of the studied individuals are often not available. For the analysis of individual genetic loci, no problem arises because the unit of interest is the observed genotype. When the unit of interest is the linear combination of alleles along one chromosome, inherited together in a haplotype, it is not always possible to determine with certainty the inheritance pattern, and therefore statistical methods to infer these patterns must be adopted. Due to genotypic heterozygosity, mutliple possible haplotype configurations can often resolve an individual's genotype measures at multiple loci. When haplotypes are not known, but are inferred statistically, an element of uncertainty is thus inherent which, if not dealt with appropriately, can result in unreliable estimates of effect sizes in an association setting. The core aim of the research described in this thesis was to develop and implement a general method for haplotype-based association analysis using multiple imputation to appropriately deal with uncertainty haplotype assignment. Regression-based approaches to association analysis provide flexible methods to investigate the influence of a covariate on a response variable, adjusting for the effects of other variables including interaction terms. ... These methods are then applied to models accommodating binary, quantitative, longitudinal and survival data. The performance of the multiple imputation method implemented was assessed using simulated data under a range of haplotypic effect sizes and genetic inheritance patterns. The multiple imputation approach performed better, on average, than ignoring haplotypic uncertainty, and provided estimates that in most cases were similar to those observed when haplotypes were known. The haplotype association methods developed in this thesis were used to investigate the genetic epidemiology of cardiovascular disease, utilising data for the cholesteryl ester transfer protein gene (CETP), the hepatic lipase (LIPC) gene and the 15- lipoxygenase (ALOX15) gene on a total of 6,487 individuals from three Western Australian studies. Results of these analyses suggested single nucleotide polymorphisms (SNPs) and haplotypes in the CETP gene were associated with increased plasma high-density lipoprotein cholesterol (HDL-C). SNPs in the LIPC gene were also associated with increased HDL-C and haplotypes in the ALOX15 gene were associated with risk of carotid plaque among individuals with premature CHD. The research presented in this thesis is both novel and important as it provides methods for the analysis of haplotypic associations with a range of response types, while incorporating information about haplotype uncertainty inherent in populationbased studies. These methods are shown to perform well for a range of simulated and real data situations, and have been written into a statistical analysis package that has been freely released to the research community.
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Krex, Dietmar, Inke R. König, Andreas Ziegler, Hans K. Schackert, and Gabriele Schackert. "Extended Single Nucleotide Polymorphism and Haplotype Analysis of the elastin Gene in Caucasians with Intracranial Aneurysms Provides Evidence for Racially/Ethnically Based Differences." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-135316.
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Background: There is growing evidence that genetic variants have an impact on the pathogenesis of intracranial aneurysm (IA). Recently, the genetic locus around the elastin gene (7q11) has been identified as linked to IA in a Japanese population. Our aim was to confirm these results in Caucasian populations. Methods: We conducted a case-control study in 120 Caucasian patients with IA and 172 controls to investigate 8 single nucleotide polymorphisms (SNPs) and various haplotypes within the elastin gene, which were frequently found and associated with the phenotype in the Japanese populations. Real-time PCR and melting curve analysis were used for the detection of genotypes. Results: Allele frequencies and genotypes were equally distributed between Caucasian cases and controls. We failed to identify haplotypes that are associated with the phenotype in our population, which is in contrast to the Japanese study. However, allele frequencies in control populations differ between Caucasians and Japanese. Conclusions: We found no association between SNPs and haplotypes of the elastin gene and the occurrence of IA in our Caucasian populations. However, our data provide strong evidence for racial/ethnic differences in the association of SNP and specific haplotypes of the elastin gene with the phenotype. There might be other genetic variants of the elastin gene associated with IA in Caucasians<br>Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich
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Krex, Dietmar, Inke R. König, Andreas Ziegler, Hans K. Schackert, and Gabriele Schackert. "Extended Single Nucleotide Polymorphism and Haplotype Analysis of the elastin Gene in Caucasians with Intracranial Aneurysms Provides Evidence for Racially/Ethnically Based Differences." Karger, 2004. https://tud.qucosa.de/id/qucosa%3A27638.
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Background: There is growing evidence that genetic variants have an impact on the pathogenesis of intracranial aneurysm (IA). Recently, the genetic locus around the elastin gene (7q11) has been identified as linked to IA in a Japanese population. Our aim was to confirm these results in Caucasian populations. Methods: We conducted a case-control study in 120 Caucasian patients with IA and 172 controls to investigate 8 single nucleotide polymorphisms (SNPs) and various haplotypes within the elastin gene, which were frequently found and associated with the phenotype in the Japanese populations. Real-time PCR and melting curve analysis were used for the detection of genotypes. Results: Allele frequencies and genotypes were equally distributed between Caucasian cases and controls. We failed to identify haplotypes that are associated with the phenotype in our population, which is in contrast to the Japanese study. However, allele frequencies in control populations differ between Caucasians and Japanese. Conclusions: We found no association between SNPs and haplotypes of the elastin gene and the occurrence of IA in our Caucasian populations. However, our data provide strong evidence for racial/ethnic differences in the association of SNP and specific haplotypes of the elastin gene with the phenotype. There might be other genetic variants of the elastin gene associated with IA in Caucasians.<br>Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.
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Yang, Yizhen. "Analyse fonctionnelle et régulation du gène HFE impliqué dans l'Hémochromatose." Brest, 2011. http://www.theses.fr/2011BRES3204.
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L’hémochromatose héréditaire se caractérise par une hyperabsorption du fer conduisant à une accumulation progressive de fer dans l’organisme. La forme majoritaire, transmise selon un mode autosomique récessif, est liée à un défaut du gène HFE, dont le rôle dans le métabolisme du fer est encore mal compris, et est associée à un bas niveau de production d’hepcidine qui régule la ferroportine, l’exporteur de fer. La substitution c. 845G>A (p. C282Y) représente 85% des chromosomes des patients atteints d’hémochromatose, et le reste des chromosomes se compose de 39% de variant c. 187C>G (p. H63D) et 4,7% de variant c. 193A>T (p. S65C), cependant ces trois variants montrent une pénétrance incomplète. Une première partie de l’étude a porté sur l’analyse du rôle de HFE dans les macrophages prélevés à partir de patients atteints d’hémochromatose et de sujets sains contrôles. Nos résultats pouffaient suggérer que la protéine HFE puisse jouer un rôle dans la balance du fer entre le cytoplasme et le lysosome, en régulant directement le flux du fer et/ou l’expression des gènes impliqués dans ce mécanisme. La forme p. C282Y non-fonctionnelle de HFE pourrait perturber cette balance et donc modifier la capacité de stockage du fer dans ces cellules. Une seconde partie concerne une étude de corrélation génotype-phénotype à l’aide de SNPs internes au gène HFE suivie d’une analyse fonctionnelle des variants SNP corrélés à une surcharge en fer. Le variant e. 187G montre un déséquilibre de liaison avec deux haplotypes représentant respectivement 79,8% et 20,2% des chromosomes porteurs ; ces haplotypes se distinguent uniquement par la variation g. 4694C>G (5’ UTR c. -467C>G). L’allèle g. 4694G est plus commua chez les patients que chez les contrôle De plus, pour les chromosomes non-mutants, un haplotype protecteur et un haplotype à risque associé à des paramètres sériques élevés en fer sont mis en évidence ces haplotypes se distinguent par les variations g. 4694C>G et c. 1007-47G>A. La faible pénétrance du variant c. 187C>G pourrait être lié au risque plus élevé de développer une surcharge pour le sous groupe de chromosomes associés à l’haplotype à risque. L’allèle g. 4694C est situé au sein d’un site putatif de réponse à l’hypoxie localisé dans la séquence promotrice du gène HFE, et nos analyses tendraient à montrer un rôle du facteur HIF dans la régulation de l’expression de HFE<br>Hereditary hemochromatosis is characterized by iron hyperabsorption leading to progressive iron overload in human body. The main form, an autosomal recessive disorder, is linked to the HFE gene defect, whose role in iron metabolism is still unclear, and is associated to a low expression of the hepcidin peptide which regulates the ferroportin iron exporter. The c. 845G>A (p. C282Y) substitution accounts for 85% of hemochromatosis patient chromosomes, the remaining chromosomes consist of 39% of c. 187C>G (p. H63D) variant and 4. 7% of the c. 193A>T (p. S65C) variant, but incomplete penetrance of the HFE mutations has been revealed. A first part of the study concerns the analysis of the role of HFE in macrophages from hemochromatosis patients and control subjects. Our results could suggest that v protein could play a role in iron balance between cytosolic and sequestered iron, by regulating iron flux and/or gene expression involved in this mechanism. The non-functional p. C282Y form may alter this balance, thereby disrupting the iron storage capacity in cells. A second part concerns a genotype-phenotype correlation study by using internal HFE SNPs, followed by functional analysis of SNP variants correlated to iron overload trait. The e. 187G variant is in linkage disequilibrium with two haplotypes accounting for 79. 8% and 20. 2%, respectively, of the carrier chromosomes; these haplotypes only diverge for the g. 4694G>C variation (5’ UTR c. 467C>G). The g. 4694G allele appeared to be more common among patients than in controls. Moreover, among non-mutant chromosomes, a protective haplotype and an at-risk haplotype associated with elevated serum iron parameters have been evidenced; these haplotypes differed only byte g. 4694C>G and c. 1007-47G>A variations. The low penetrance of the e. 187G mutation could thus be related to the increased risk for developing iron overload trait from a subset of e. 187G chromosomes associated with the risk haplotype. The g. 4694C allele is located within a putative hypoxiaresponse element of the HFE promoter sequence, and our analyses tend to show a role of the hypoxia HIF factor in the regulation of HFE expression
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Giovanni, Monica A. "A Family-Based Mapping Study of Autosomal Dominant Nonsyndromic Sensorineural Hearing Loss." University of Cincinnati / OhioLINK, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1179241536.
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Jäger, Jan Christian [Verfasser], and Roland [Akademischer Betreuer] Martin. "Analyse der funktionellen Relevanz unterschiedlicher Interleukin-7 Rezeptor Alpha Haplotypen für die Ätiologie und Pathogenese der Multiplen Sklerose / Jan Christian Jäger. Betreuer: Roland Martin." Hamburg : Staats- und Universitätsbibliothek Hamburg, 2012. http://d-nb.info/1024772780/34.
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Lembring, Maria. "Application of Mitochondrial DNA Analysis in Contemporary and Historical Samples." Doctoral thesis, Uppsala universitet, Genomik, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-209970.
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The mitochondrion is a tiny organelle that is the power supplier of the cell and vital to the functioning of the body organs. Additionally it contains a small circular genome of about 16 kb, present in many copies which makes the mitochondrial DNA more viable than nuclear DNA. Mitochondrial DNA is also maternally inherited and thus provides a direct link to maternal relatives. These two properties are of particular use for forensic samples, which only contain limited or degraded amounts of DNA, and for historical samples (ancient DNA). This thesis presents work on the mitochondrial DNA in the hypervariable regions (HV) I and II, in both contemporary and historical samples. Forensic genetics makes use of mitochondrial DNA analysis in court as circumstantial evidence, and population databases are used for the calculation of evidence value. Population samples (299) across Sweden have been analysed in order to enrich the EDNAP mtDNA database (EMPOP) (paper I). The application of mitochondrial DNA analysis allowed for analysis of historical skeletal remains: Copernicus, 1473-1543 (paper II), Karin Göring, 1888-1931 (paper III) and Medieval bones, 880-1000 AD, from a mass grave found in Sigtuna, Sweden (paper IV). The thesis also includes analyses of bones and teeth from the shipwrecked crew of the Vasa warship, 1628, samples from the Vasa museum, Stockholm, Sweden (paper V). Overall, the varying age of the samples and the different conservation environments (soil and water) accounted for variations in quality, but still allowed for successful DNA analysis.
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Fowler, Elizabeth Victoria. "Genetic analysis of the koala (Phascolarctos cinerus)." Thesis, Queensland University of Technology, 1999.
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Matos, Camacho Stephan. "Introduction to the Minimum Rainbow Subgraph problem." Doctoral thesis, Technische Universitaet Bergakademie Freiberg Universitaetsbibliothek "Georgius Agricola", 2012. http://nbn-resolving.de/urn:nbn:de:bsz:105-qucosa-85490.
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Arisen from the Pure Parsimony Haplotyping problem in the bioinformatics, we developed the Minimum Rainbow Subgraph problem (MRS problem): Given a graph $G$, whose edges are coloured with $p$ colours. Find a subgraph $F\\\\subseteq G$ of $G$ of minimum order and with $p$ edges such that each colour occurs exactly once. We proved that this problem is NP-hard, and even APX-hard. Furthermore, we stated upper and lower bounds on the order of such minimum rainbow subgraphs. Several polynomial-time approximation algorithms concerning their approximation ratio and complexity were discussed. Therefore, we used Greedy approaches, or introduced the local colour density $\\\\lcd(T,S)$, giving a ratio on the number of colours and the number of vertices between two subgraphs $S,T\\\\subseteq G$ of $G$. Also, we took a closer look at graphs corresponding to the original haplotyping problem and discussed their special structure.
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Braz, Camila Urbano [UNESP]. "Detecção de QTL para maciez da carne em bovinos da raça Nelore." Universidade Estadual Paulista (UNESP), 2016. http://hdl.handle.net/11449/143485.
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Previous issue date: 2016-07-29<br>Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)<br>O mercado consumidor tem sido cada vez mais exigente quanto à qualidade da carne e, portanto, a pecuária precisa melhorar sua eficiência e fornecer produtos diferenciados, padronizados e com qualidade. Entre as características de qualidade de carne, a maciez é a que mais influencia na satisfação dos consumidores. Considerando a importância dada à maciez da carne, pesquisas têm sido desenvolvidas para melhor compreender os mecanismos relacionados à expressão fenotípica desta característica. Os estudos de genes candidatos têm possibilitado a identificação de polimorfismos que modificam as estruturas das proteínas ou ainda, que estejam em desequilíbrio de ligação com alterações funcionais no DNA. Com a automatização dos polimorfismos de nucleotídeo único (SNPs) muitas regiões ao longo do genoma foram identificadas como responsáveis pela variação fenotípica da maciez da carne. No entanto, os marcadores SNPs podem ter baixa capacidade de identificar locos que atuam nas características quantitativas (QTL) por serem, na grande maioria, bi-alélicos e, mesmo que aconteçam mutações, as mudanças nas frequências alélicas dos SNPs podem permanecer quase inalteradas. Por outro lado, com a utilização de haplótipos, mutações tendem a causar mudanças nas frequências dos haplótipos, aumentando as chances de identificação dos QTL. Sendo assim, este estudo teve como objetivos detectar QTL e mutações causais em genes candidatos e identificar QTL por meio de uma análise de associação genômica ampla, para a característica maciez da carne em bovinos da raça Nelore, utilizando haplótipos como unidades fundamentais dos testes de associação. Foram utilizadas informações fenotípicas, genotípicas e de pedigree de animais provenientes de fazendas que integram os programas de melhoramento genético DeltaGen e PAINT. Cinquenta e dois genes candidatos foram escolhidos para serem analisados utilizando haplótipos construídos com base no desequilíbrio de ligação, utilizando 1.616 animais. Do total de haplótipos, dois foram significativos, sendo que os éxons próximos e dentro destes foram sequenciados visando buscar a mutação causal. O sequenciamento foi realizado com 298 animais e os SNPs identificados foram imputados para os 1.318 animais remanescentes. Foram realizadas análises de associação utilizando haplótipos construídos com base na metodologia de janelas sobrepostas, sendo que seus efeitos foram estimados pelo método Genomic Best Linear Unbiased Predictor (GBLUP). Os valores genéticos dos animais foram estimados para cada haplótipo e SNP e, após, as variâncias genéticas aditivas foram calculadas. Utilizando haplótipos construídos com base em janelas sobrepostas, verificou-se que o aumento do número de SNPs no haplótipo permitiu capturar maior proporção da variância genética aditiva da característica maciez da carne. Seis possíveis QTL foram identificados explicando as maiores proporções de variância genética aditiva para maciez da carne, dos quais um está no gene CAPN1 e cinco no gene ASAP1. Não houve evidências de que a mutação causal para a maciez da carne tenha sido identificada nos dois genes. Uma análise de associação genômica ampla foi realizada utilizando haplótipos construídos com base na metodologia de janelas sobrepostas de tamanhos variados. Foram utilizados nesta análise 1.405 animais genotipados com o painel Illumina Bovine HD e 1.756 animais genotipados com painel de menor densidade (70 K Neogen) e, posteriormente, imputados para o painel HD, em um total de 3.161 animais analisados. Os efeitos dos haplótipos e SNPs foram estimados pelo método GBLUP e as variâncias genética aditivas de cada haplótipo e SNP foram calculadas. Os genes NOS1AP, SUCLG1, PHLDB2 e LOC107132946 foram associados com a característica maciez da carne em bovinos da raça Nelore, por meio de análises de associação genômica ampla utilizando SNPs individuais e haplótipos. A análise utilizando SNPs identificou QTL diferentes das análises com haplótipos e, em alguns casos, SNPs apresentaram variâncias genéticas aditivas maiores do que as apresentadas pelos haplótipos. A análise que utilizou haplótipos construídos com cinco SNPs identificou mais QTL do que as análises de haplótipos construídos com sete e nove SNPs. Sugere-se que análises utilizando haplótipos, baseados em janelas sobrepostas, sejam realizadas para complementar análises de SNPs individuais em estudos de associação genômica ampla.<br>The consumer market has been increasingly demanding about the meat quality and therefore livestock needs to improve its efficiency and provide differentiated products, standardized and with quality. Considering the importance given to the meat tenderness, research has been undertaken to better understand the mechanisms related to the phenotypic expression of this trait. The candidate gene studies have allowed the identification of polymorphisms that change the structures of the proteins or that are in linkage disequilibrium with functional alterations in the DNA. With the advent of single nucleotide polymorphisms (SNPs) throughout many regions of the genome have been identified as responsible for phenotypic variation in meat tenderness. However, SNPs markers may have low ability to identify mutations, because SNPs are commonly bi-allelic and even when mutations have occurred, allelic frequencies can remain unaltered. On the other hand, using haplotype, mutations tend to cause major changes in haplotype frequencies, increasing the chances of identification of QTL. Thus, this study aimed to detect QTL and causal mutations by the approach of candidate genes and identify possible QTL through a genome-wide association analysis, for the trait meat tenderness in Nelore cattle using haplotypes as fundamental units of association tests. Information of the phenotypic, genotypic and pedigree were used from farms that belong to the breeding programs DeltaGen and PAINT. Fifty-two candidate genes were chosen for analysis using haplotypes constructed based on linkage disequilibrium using 1,616 animals. Two haplotypes were significant, and the exons near and within these haplotypes were sequenced to search for the causal mutation. The sequencing was performed using 298 animals and the identified SNPs were imputed for 1,318 remaining animals. Association analysis using haplotypes constructed based on the method of overlapping sliding windows were carried out and the SNPs and haplotypes effects were estimated using Genomic Best Linear Unbiased Predictor (GBLUP) method. The breeding values were estimated for each haplotype and SNPs and the additive genetic variances were calculated. Using haplotypes constructed based on overlapping sliding windows, we found that increasing the number of SNPs in the haplotype allowed to capture a greater proportion of additive genetic variance of meat tenderness. Six putative QTL were identified with the greatest additive genetic variances for meat tenderness, which one was in CAPN1 gene and five in ASAP1 gene. There was no evidence that the causal mutation for meat tenderness trait has been identified in these genes. A genome-wide association analysis was performed using haplotypes constructed based on the methodology of overlapping sliding windows of varying sizes. In this analysis, 1,405 animals genotyped with the Illumina Bovine HD panel and 1,756 genotyped animals with lower density panel (Neogen 70 K) were used and then, the genotypes of the 1,756 were imputed to the HD panel, in a total of 3,161 animals analyzed. The haplotypes and SNPs effects were estimated by the method GBLUP and the additive genetic variances were calculated for each haplotype and SNP. The NOS1AP, SUCLG1, PHLDB2 and LOC107132946 genes were associated with the meat tenderness trait in Nelore cattle through genome-wide association analysis using individual SNPs and haplotypes. The analysis using SNPs identified different QTL of the haplotype analyzes, and in some cases, the SNPs showed additive genetic variance greater than those presented by the haplotypes. The analysis used haplotypes constructed with five SNPs identified more QTL than analysis of haplotypes constructed with seven and nine SNPs. Analyzes using haplotypes based on overlapping sliding windows, should be conducted as additional analyzes for individual SNPs in genome-wide association studies.<br>FAPESP: 2013/00035-9
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Morcillo, Suárez Carlos. "Analysis of genetic polymorphisms for statistical genomics: tools and applications." Doctoral thesis, Universitat Pompeu Fabra, 2011. http://hdl.handle.net/10803/78126.
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New approaches are needed to manage and analyze the enormous quantity of biological data generated by modern technologies. Existing solutions are often fragmented and uncoordinated and, thus, they require considerable bioinformatics skills from users. Three applications have been developed illustrating different strategies to help users without extensive IT knowledge to take maximum profit from their data.
SNPator is an easy-to-use suite that integrates all the usual tools for genetic association studies: from initial quality control procedures to final statistical analysis. CHAVA is an interactive visual application for CNV calling from aCGH data. It presents data in a visual way that helps assessing the quality of the calling and assists in the process of optimization. Haplotype Association Pattern Analysis visually presents data from exhaustive genomic haplotype associations, so that users can recognize patterns of possible associations that cannot be detected by single-SNP tests.<br>Calen noves aproximacions per la gestió i anàlisi de les enormes quantitats de dades biològiques generades per les tecnologies modernes. Les solucions existents, sovint fragmentaries i descoordinades, requereixen elevats nivells de formació bioinformàtica. Hem desenvolupat tres aplicacions que il•lustren diferents estratègies per ajudar als usuaris no experts en informàtica a aprofitar al màxim les seves dades.
SNPator és un paquet de fàcil us que integra les eines usades habitualment en estudis de associació genètica: des del control de qualitat fins les anàlisi estadístiques. CHAVA és una aplicació visual interactiva per a la determinació de CNVs a partir de dades aCGH. Presenta les dades visualment per ajudar a valorar la qualitat de les CNV predites i ajudar a optimitzar-la. Haplotype Pattern Analysis presenta dades d’anàlisi d’associació haplotípica de forma visual per tal que els usuaris puguin reconèixer patrons de associacions que no es possible detectar amb tests de SNPs individuals.
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Pecheniuk, Natalie Maria. "DNA analysis of common genetic variations which predispose to thrombophilia." Thesis, Queensland University of Technology, 2000.
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