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1
Faure, Roland. "Haplotype assembly from long reads". Electronic Thesis or Diss., Université de Rennes (2023-....), 2024. http://www.theses.fr/2024URENS052.
Testo completoAbstract (sommario):
Cette thèse propose des solutions pour améliorer l'assemblage des génomes à partir de lectures de séquençage de troisième génération (lectures longues). Plus précisément, elle se concentre sur l'amélioration de l'assemblage des (méta)génomes contenant plusieurs haplotypes, comme des génomes polyploïdes ou des souches bactériennes proches. Les assembleurs actuels ont du mal à séparer les haplotypes très similaires, et fusionnent généralement des (parties d')haplotypes, ce qui entraîne la perte de polymorphismes et d'hétérozygotie dans l'assemblage final. Ce travail présente une série de méthodes et de logiciels pour obtenir des assemblages contenant des haplotypes bien séparés. Plus précisément, GenomeTailor et HairSplitter transforment un assemblage obtenu avec des lectures longues erronées en un assemblage phasé, améliorant considérablement l'état de l'art lorsque de nombreuses souches sont présentes. Le logiciel Alice propose une nouvelle méthode, basée sur des nouveaux sketchs ``MSR'', pour assembler efficacement plusieurs haplotypes séquencés avec des lectures de haute fidélité. Enfin, cette thèse propose une nouvelle stratégie de scaffolding Hi-C basée sur le démêlage des graphes d'assemblage qui améliore considérablement les assemblages finaux, en particulier lorsque plusieurs haplotypes sont présentsThis thesis presents solutions to improve genome assembly from third-generation sequencing reads, with a specific focus on improving the assembly of (meta)genomes containing multiple haplotypes, such as polyploid genomes or close bacterial strains. Current assemblers struggle to separate highly similar haplotypes, often collapsing all or parts of the haplotypes into one, thereby discarding polymorphisms and heterozygosity. This work introduces a series of methods and software tools to achieve haplotype-separated assemblies. Specifically, GenomeTailor and HairSplitter transform a collapsed assembly obtained with erroneous long reads into a phased assembly, significantly improving on the state of the art when numerous strains are present. The software Alice introduces a new method based on the new ``MSR'' sketching technique for efficiently assembling multiple haplotypes sequenced with high-fidelity reads. Additionally, this thesis proposes a new Hi-C scaffolding strategy that involves untangling assembly graphs which significantly improves final assemblies, particularly when several haplotypes are present
2
Angulo, Rafael Villa. "Computational methods for haplotype inference with application to haplotype block characterization in cattle". Fairfax, VA : George Mason University, 2009. http://hdl.handle.net/1920/4558.
Testo completoAbstract (sommario):
Thesis (Ph.D.)--George Mason University, 2009.Vita: p. 123. Thesis director: John J. Grefenstette. Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Bioinformatics and Computational Biology. Title from PDF t.p. (viewed Sept. 8, 2009). Includes bibliographical references (p. 114-122). Also issued in print.
3
Beucher, Julie. "Haplotype ancestral AH8.1 dans la mucoviscidose". Phd thesis, Université Pierre et Marie Curie - Paris VI, 2012. http://tel.archives-ouvertes.fr/tel-00827653.
Testo completoAbstract (sommario):
La mucoviscidose est une maladie à transmission autosomique récessive, due à des mutations du gène CFTR. Les patients, partageant de mêmes mutations de CFTR et un même environnement, ont une expression phénotypique variable, suggérant l'influence d'autres gènes modifiant la sévérité de la maladie, appelés gènes modificateurs. L'atteinte respiratoire, caractérisée par une inflammation exacerbée, est un facteur principal de morbimortalité. L'haplotype ancestral AH8.1, impliqué dans la réponse inflammatoire, est constitué de 4 variants : LTa +252A/G, TNF -308G/A, HSPA1B +1267A/G et AGER -429T/C. Ainsi, l'objectif était de rechercher une association entre l'haplotype AH8.1 et la sévérité de l'atteinte respiratoire. Nous avons montré dans une cohorte de 404 patients européens, porteurs de différentes mutations de CFTR, que AH8.1 était associé au déclin de la fonction respiratoire. Nous avons taché de répliquer nos résultats dans une cohorte homogène de 1089 patients français, F508del homozygotes, sans succès à ce jour. Nous poursuivons cette étude chez des patients porteurs d'autres mutations de CFTR. Les variants de cet haplotype ont également été étudié séparément. Nous avons ainsi montré que AGER-429T/C, non seulement modulait la sévérité de l'atteinte respiratoire, mais, était également associé in vitro à une plus grande production de la protéine RAGE. L'ensemble de ces résultats suggère à ce jour que l'haplotype AH8.1 pourrait moduler la sévérité de l'atteinte respiratoire des patients non homozygotes pour la mutation CFTR F508del. De plus, le variant AGER-429T/C seul, modulant la sévérité de l'atteinte respiratoire, la protéine RAGE pourrait être envisagée comme biomarqueur dans la mucoviscidose. Mots clés : mucoviscidose - gène modificateur - haplotype ancestral AH8.1 - RAGE
4
Rogers, Emma Jayne. "Haplotype evolution and human genetic diversity". Thesis, University of Nottingham, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.342507.
Testo completo
5
Xu, Xiao. "Human alpha defensin CNV haplotype diversity". Thesis, University of Nottingham, 2018. http://eprints.nottingham.ac.uk/51262/.
Testo completoAbstract (sommario):
Humans have highly variable number of alpha defensin genes, with between 3-16 diploid copies. Alpha-defensin genes have important roles in human innate immunity and diseases. Recently, GWAS studies reported this locus associated with IgA nephropathy and periodontitis. However, the underlying mechanism of association is not clear. In this Ph.D. thesis, human alpha defensin CNV flanking haplotype diversity in global populations was studied and the association between diseases and haplotype classes was discussed. Then a novo method to detect variants from inside the DEFA1A3 CNV was developed and a list of potential disease-related mutations for further functional studies was generated. The association between CNV internal variants and flanking haplotype classes was studied. Non-allelic homologous recombination was found to be the major mechanism of CNV formation of alpha defensin CNV. Analysis results were verified by PCR and Sanger sequencing-based methods. Additional to that, the haplotype diversity analysis highlighted an unusual haplotype 5T/7C which is only found in European populations but highly diverged from other human haplotypes. Further evidence was provided to suggest that this is an introgressed haplotype from Neanderthals. Furthermore, we used Oxford Nanopore to reconstruct haplotype structure in DEFA1A3 CNV and discussed its advantages and limitations by our analysis results. In brief, this Ph.D. research greatly improved our understanding of DEFA1A3 global diversity, evolutionary history, diseases and haplotype association.
6
Huang, Bevan Emma Lin Danyu. "Statistical aspects of haplotype-based association studies". Chapel Hill, N.C. : University of North Carolina at Chapel Hill, 2007. http://dc.lib.unc.edu/u?/etd,1237.
Testo completoAbstract (sommario):
Thesis (Ph. D.)--University of North Carolina at Chapel Hill, 2007.Title from electronic title page (viewed Mar. 26, 2008). "... in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Biostatistics, School of Public Health." Discipline: Biostatistics; Department/School: Public Health.
7
Zhang, Jun. "Genotype/Haplotype Tagging Methods and their Validation". Digital Archive @ GSU, 2007. http://digitalarchive.gsu.edu/cs_theses/51.
Testo completoAbstract (sommario):
This study focuses how the MLR-tagging for statistical covering, i.e. either maximizing average R2 for certain number of requested tags or minimizing number of tags such that for any non-tag SNP there exists a highly correlated (squared correlation R2 > 0.8) tag SNP. We compare with tagger, a software for selecting tags in hapMap project. MLR-tagging needs less number of tags than tagger in all 6 cases of the given test sets except 2. Meanwhile, Biologists can detect or collect data only from a small set. So, this will bring a problem for scientists that the estimates accuracy of tag SNPs when constructing the complete human haplotype map. This study investigates how the MLR-tagging for statistically coverage performs under unbias study. The experiment results shows MLR-tagging still select small amount of SNPs very well even without observing the entire SNP in the sample.
8
Vijaya, Satya Ravi. "ALGORITHMS FOR HAPLOTYPE INFERENCE AND BLOCK PARTITIONING". Doctoral diss., University of Central Florida, 2006. http://digital.library.ucf.edu/cdm/ref/collection/ETD/id/2490.
Testo completoAbstract (sommario):
The completion of the human genome project in 2003 paved the way for studies to better understand and catalog variation in the human genome. The International HapMap Project was started in 2002 with the aim of identifying genetic variation in the human genome and studying the distribution of genetic variation across populations of individuals. The information collected by the HapMap project will enable researchers in associating genetic variations with phenotypic variations. Single Nucleotide Polymorphisms (SNPs) are loci in the genome where two individuals differ in a single base. It is estimated that there are approximately ten million SNPs in the human genome. These ten million SNPS are not completely independent of each other - blocks (contiguous regions) of neighboring SNPs on the same chromosome are inherited together. The pattern of SNPs on a block of the chromosome is called a haplotype. Each block might contain a large number of SNPs, but a small subset of these SNPs are sufficient to uniquely dentify each haplotype in the block. The haplotype map or HapMap is a map of these haplotype blocks. Haplotypes, rather than individual SNP alleles are expected to effect a disease phenotype. The human genome is diploid, meaning that in each cell there are two copies of each chromosome - i.e., each individual has two haplotypes in any region of the chromosome. With the current technology, the cost associated with empirically collecting haplotype data is prohibitively expensive. Therefore, the un-ordered bi-allelic genotype data is collected experimentally. The genotype data gives the two alleles in each SNP locus in an individual, but does not give information about which allele is on which copy of the chromosome. This necessitates computational techniques for inferring haplotypes from genotype data. This computational problem is called the haplotype inference problem. Many statistical approaches have been developed for the haplotype inference problem. Some of these statistical methods have been shown to be reasonably accurate on real genotype data. However, these techniques are very computation-intensive. With the international HapMap project collecting information from nearly 10 million SNPs, and with association studies involving thousands of individuals being undertaken, there is a need for more efficient methods for haplotype inference. This dissertation is an effort to develop efficient perfect phylogeny based combinatorial algorithms for haplotype inference. The perfect phylogeny haplotyping (PPH) problem is to derive a set of haplotypes for a given set of genotypes with the condition that the haplotypes describe a perfect phylogeny. The perfect phylogeny approach to haplotype inference is applicable to the human genome due to the block structure of the human genome. An important contribution of this dissertation is an optimal O(nm) time algorithm for the PPH problem, where n is the number of genotypes and m is the number of SNPs involved. The complexity of the earlier algorithms for this problem was O(nm^2). The O(nm) complexity was achieved by applying some transformations on the input data and by making use of the FlexTree data structure that has been developed as part of this dissertation work, which represents all the possible PPH solution for a given set of genotypes. Real genotype data does not always admit a perfect phylogeny, even within a block of the human genome. Therefore, it is necessary to extend the perfect phylogeny approach to accommodate deviations from perfect phylogeny. Deviations from perfect phylogeny might occur because of recombination events and repeated or back mutations (also referred to as homoplasy events). Another contribution of this dissertation is a set of fixed-parameter tractable algorithms for constructing near-perfect phylogenies with homoplasy events. For the problem of constructing a near perfect phylogeny with q homoplasy events, the algorithm presented here takes O(nm^2+m^(n+m)) time. Empirical analysis on simulated data shows that this algorithm produces more accurate results than PHASE (a popular haplotype inference program), while being approximately 1000 times faster than phase. Another important problem while dealing real genotype or haplotype data is the presence of missing entries. The Incomplete Perfect Phylogeny (IPP) problem is to construct a perfect phylogeny on a set of haplotypes with missing entries. The Incomplete Perfect Phylogeny Haplotyping (IPPH) problem is to construct a perfect phylogeny on a set of genotypes with missing entries. Both the IPP and IPPH problems have been shown to be NP-hard. The earlier approaches for both of these problems dealt with restricted versions of the problem, where the root is either available or can be trivially re-constructed from the data, or certain assumptions were made about the data. We make some novel observations about these problems, and present efficient algorithms for unrestricted versions of these problems. The algorithms have worst-case exponential time complexity, but have been shown to be very fast on practical instances of the problem.Ph.D.
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Engineering and Computer Science
Computer Science
9
Cavalleri, Gianpiero. "Haplotype mapping in epilepsy genetics and pharmacogenetics". Thesis, University College London (University of London), 2006. http://discovery.ucl.ac.uk/1445351/.
Testo completoAbstract (sommario):
Despite the success achieved in identifying mutations causing Mendelian forms of epilepsy, little progress has been made in illuminating variation contributing to the development of more common forms of the condition. The aim of this thesis was to improve methodology that would aid the detection of variation functional in the development and treatment of common forms of epilepsy. Attempted replication of previous claims of association with common forms of epilepsy allowed resolution of true effects from false positive results and illustrated shortcomings in the application of association based genetic mapping. Where effects looked real, haplotype-based fine mapping techniques were applied to identify candidate causal variation. The tagging SNP method was applied to HapMap data in an attempt to identify variation that might guide the safe prescription of Vigabatrin, an effective antiepileptic drug limited by a serious adverse drug reaction. Results outlined here show all previous claims of association with temporal lobe epilepsy and febrile seizures are likely to be false positives. However, supportive evidence is presented that common genetic variation predisposes to juvenile myoclonic epilepsy in a population specific manner. Evidence is also presented that variation that could be considered clinically relevant for the safe administration of Vigabatrin does not exist in the candidate genes examined here. Finally, a study design is proposed that seeks to significantly increase genetic power of detection through the incorporation of lessons learned from previous studies. In conclusion, epilepsy appears to be as genetically complex as the phenotypic spectrum of the condition would suggest. This work illustrates key areas in study design that require improvement and presents methodological developments in genetic mapping techniques which together provide a solid platform for future success.
10
Beucher, Julie. "Haplotype ancestral AH8. 1 dans la mucoviscidose". Paris 6, 2012. http://www.theses.fr/2012PA066142.
Testo completoAbstract (sommario):
La mucoviscidose est une maladie à transmission autosomique récessive, due à des mutations du gène CFTR. Les patients, partageant de mêmes mutations de CFTR et un même environnement, ont une expression phénotypique variable, suggérant l'influence d’autres gènes modifiant la sévérité de la maladie, appelés gènes modificateurs. L’atteinte respiratoire, caractérisée par une inflammation exacerbée, est un facteur principal de morbi-mortalité. L’haplotype ancestral AH8. 1, impliqué dans la réponse inflammatoire, est constitué de 4 variants : LTa +252A/G, TNF -308G/A, HSPA1B +1267A/G et AGER -429T/C. Ainsi, l’objectif était de rechercher une association entre l’haplotype AH8. 1 et la sévérité de l’atteinte respiratoire. Nous avons montré dans une cohorte de 404 patients européens, porteurs de différentes mutations de CFTR, que AH8. 1 était associé au déclin de la fonction respiratoire. Nous avons taché de répliquer nos résultats dans une cohorte homogène de 1089 patients français, F508del homozygotes, sans succès à ce jour. Nous poursuivons cette étude chez des patients porteurs d’autres mutations de CFTR. Les variants de cet haplotype ont également été étudié séparément. Nous avons ainsi montré que AGER-429T/C, non seulement modulait la sévérité de l’atteinte respiratoire, mais, était également associé in vitro à une plus grande production de la protéine RAGE. L’ensemble de ces résultats suggère à ce jour que l’haplotype AH8. 1 pourrait moduler la sévérité de l’atteinte respiratoire des patients non homozygotes pour la mutation CFTR F508del. De plus, le variant AGER-429T/C seul, modulant la sévérité de l’atteinte respiratoire, la protéine RAGE pourrait être envisagée comme biomarqueur dans la mucoviscidoseCystic fibrosis is an autosomic recessive disease due to mutations in the gene CFTR. There is a great phenotypic variability among patients with identical mutations and with identical environment. These data suggest that others genes, called modifier genes, may affect the lung phenotype. Lung disease, characterized by airway inflammation, is a key component of morbi-mortality. The ancestral haplotype AH8. 1, involved in the inflammatory response, is composed of 4 variants: LTa +252A/G, TNF -308G/A, HSPA1B +1267A/G and AGER -429T/C. The aim of the study was to test whether this haplotype AH8. 1 was associated with lung disease severity in cystic fibrosis. We showed in a cohort of 404 European patients, carriers of different mutations of CFTR, that AH8. 1 is associated with a greater lung disease severity. We did not succeed to replicate our results in a homogeneous cohort of 1039 French patients F508del homozygotes. We proceed with this study in patients, carriers of other CFTR mutations. Variants of this haplotype were also studied separately. We have shown that AGER-429T/C, not only modulates the severity of lung disease, but was also associated in vitro with a greater production of the protein RAGE. All these results suggest to date that AH8. 1 haplotype could modulate the lung disease severity in patients not homozygous for the F508del CFTR mutation. Moreover, the variant AGER-429T/C modulated the lung disease severity and the protein RAGE may be considered as a biomarker in cystic fibrosis
11
Ayers, Kristin Lynn. "Methods for haplotype construction and their applications". Diss., Restricted to subscribing institutions, 2008. http://proquest.umi.com/pqdweb?did=1568065851&sid=1&Fmt=2&clientId=1564&RQT=309&VName=PQD.
Testo completo
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Pan, Xiaoyue. "Haplotype Inference by Pure Parsimony with Constraint Programming". Thesis, Uppsala University, Department of Information Technology, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-110544.
Testo completoAbstract (sommario):
Haplotype inference by pure parsimony problem (HIPP) is a computational problem in bioinformatics. It is a relatively new NP-hard problem and it has been thoroughly explored using integer programming, SAT-based programming and answer set programming. The state of the art approach is the SAT-based model. Constraint programming has been used as an optimisation tool in the SAT-based model but it has not been used as the modelling tool to solve the problem. This thesis models the HIPP problem using constraint programming. The constraint models are not as efficient as the SAT-based model but provides an alternative of modelling the problem.
13
Labarre, Anthony. "Combinatorial aspects of genome rearrangements and haplotype networks". Phd thesis, Universite Libre de Bruxelles, 2008. http://tel.archives-ouvertes.fr/tel-00482196.
Testo completoAbstract (sommario):
La thèse couvre deux problèmes motivés par la biologie: l'étude des réarrangements génomiques, et celle des réseaux d'haplotypes. Les problèmes de réarrangements génomiques sont un cas particulier des problèmes de distances d'édition, où l'on cherche à transformer un objet en un autre en utilisant le plus petit nombre possible d'opérations, les opérations autorisées étant fixées au préalable; on s'intéresse également à la distance entre les deux objets, c'est-à-dire au calcul du nombre d'opérations dans une séquence optimale plutôt qu'à la recherche d'une telle séquence. Les problèmes de réarrangements génomiques peuvent souvent s'exprimer comme des problèmes de tri de permutations (vues comme des arrangements linéaires de {1,2,...,n}) en utilisant le plus petit nombre d'opérations (autorisées) possible. Nous examinons en particulier les ``transpositions', qui déplacent un intervalle de la permutation. Beaucoup de problèmes liés au tri par transpositions sont ouverts, en particulier sa complexité algorithmique. Nous nous écartons des ``outils standards' utilisés dans le domaine des réarrangements génomiques, et utilisons la décomposition en cycles disjoints des permutations pour prouver de nouvelles majorations sur la distance des transpositions ainsi que des formules permettant de calculer cette distance en temps polynomial dans de nombreux cas. Cette décomposition nous sert également à résoudre un problème d'énumération concernant le ``graphe des cycles' de Bafna et Pevzner, et à construire une technique générale permettant d'obtenir de nouvelles minorations en reformulant tous les problèmes de distances d'édition sur les permutations en termes de factorisations de permutations paires associées. Les réseaux d'haplotypes sont des graphes dont une partie des sommets porte des étiquettes, utilisés en génomique comparative quand les arbres sont trop restrictifs, ou quand l'on ne peut choisir une ``meilleure' topologie parmi un ensemble donné d'arbres. Nous formalisons une nouvelle méthode due à Cassens, Mardulyn et Milinkovitch, qui consiste à construire un graphe contenant tous les arbres partiellement étiquetés donnés et possédant le moins d'arêtes possible, et donnons des algorithmes résolvant le problème de manière optimale sur deux graphes, dont le temps d'exécution est exponentiel en général mais polynomial dans quelques cas que nous caractérisons.
14
Durrant, Caroline. "Haplotype clustering methods : application to disease gene mapping". Thesis, University of Oxford, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.432561.
Testo completo
15
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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16
Tai, Bik-wah Diana, e 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.
Testo completo
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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.
Testo completoAbstract (sommario):
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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.
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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PHATAK, MUKTA. "OPTIMAL SOLUTION TO HAPLOTYPE INFERENCE USING PARSIMONY MODEL". University of Cincinnati / OhioLINK, 2004. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1092940172.
Testo completo
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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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20
Li, Xin. "Haplotype Inference from Pedigree Data and Population Data". Cleveland, Ohio : Case Western Reserve University, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=case1259867573.
Testo completoAbstract (sommario):
Thesis(Ph.D.)--Case Western Reserve University, 2010Title from PDF (viewed on 2009-12-30) Department of Electrical Engineering and Computer Science Includes abstract Includes bibliographical references and appendices Available online via the OhioLINK ETD Center
21
Nothnagel, Michael. "The definition of multilocus haplotype blocks and common diseases". [S.l.] : [s.n.], 2004. http://deposit.ddb.de/cgi-bin/dokserv?idn=973611448.
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22
Backeman, Peter. "Propagating the nVector Constraint : Haplotype Inference using Constraint Programming". Thesis, Uppsala universitet, Institutionen för informationsteknologi, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-211862.
Testo completoAbstract (sommario):
Genetics research is a wide field and needs computer aid in many different areas. One such problem is the haplotype inference problem by pure parsimony (HIPP). In this thesis the HIPP problem is attacked with a constraint programming (CP) model based on the nVector constraint, for which a new propagator is designed. The results show that the current state-of-the-art model based on SAT-solvers are in general the most efficient, but that the CP approach in some cases finds a better solution when time is limited.
23
Smith, Joel Haviland. "Leveraging Haplotype-Based Inference to Describe Adaptation and Speciation". Thesis, The University of Chicago, 2018. http://pqdtopen.proquest.com/#viewpdf?dispub=10788183.
Testo completoAbstract (sommario):
Forward progress in empirical population genetics is closely tied to the development of theory which can accomodate and keep pace with the production of genetic data. In recent years, the ability to survey genetic variation at increasingly greater resolution, across the genomes of a variety of species, has prompted new approaches to use this data for population genetic inference. While many models have historically relied on assuming independence among genetic variants in a sample of chromosomes, there are now a variety of methods which can use the non-independence among variants as a source of information. In particular, the unique combination and co-inheritance of variants on a chromosome can be used to define "haplotypes" of linked genetic variation associated with specific populations, individuals, or variants from which they are descended. The work presented here is a contribution to this class of population genetic models which describes: (1) a method to estimate the timing of adaptation for a beneficial allele, including several applications to recent human evolution, (2) an application of the same method to infer the timing of introgression for coat color alleles in North American wolves and high-altitude adaptation in Tibetans, (3) a model to infer the action of purifying selection against genetic incompatibilities in a hybrid zone, and (4) a reanalysis of genomic data from Heliconius butterflies which confirms the role of hybridization in transfering mimicry phenotypes between species.
24
Sinha, Moumita. "ESTIMATION OF HAPLOTYPE FREQUENCIES FROM DATA ON UNRELATED PEOPLE". Case Western Reserve University School of Graduate Studies / OhioLINK, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=case1164801319.
Testo completo
25
Nothnagel, Michael. "The definition of multilocus haplotype blocks and common diseases". Doctoral thesis, Humboldt-Universität zu Berlin, Medizinische Fakultät - Universitätsklinikum Charité, 2005. http://dx.doi.org/10.18452/15174.
Testo completoAbstract (sommario):
Bisherige Methoden der Haplotyp-Block-Definition zielen entweder auf abwesende Rekombinationsereignisse oder eine effiziente Beschreibung genomischer Variation. Die vorliegende Arbeit definiert Blöcke von Single Nucleotide Polymorphisms (SNP) als Gebiete erhöhten Kopplungsungleichgewichtes (LD). Für dieses Ziel wird ein neues, entropie-basiertes Maß für LD zwischen multiplen Markern/Loci (Normalized Entropy Difference) entwickelt und als eine Multilocus-Erweiterung des paarweisen Maßes r2 charakterisiert. Ein zugehöriger Algorithmus für die Block-Definition wird vorgeschlagen. Seine Evaluierung an einem Datensatz des menschlichen Chromosoms 12 vom Internationalen Haplotype Map Projekt zeigt die Nützlichkeit der abgeleiteten Blöcke in Hinblick auf verschiedene Eigenschaften, einschließlich ihrer chromosomalen Coverage und der Anzahl sowie des Anteils der häufigen Block-Haplotypen. Der wesentliche Einfluß der SNP-Dichte auf die zu entdeckenden LD- und Blockstrukturen wird demonstriert. Der Erfolg von Assoziationsstudien in komplexen Erkrankungen mit Block-Haplotypen als multiallelischen Markern wird davon abhängen, ob die Common Variants/Common Diseases (CV/CD) Hypothese für solche Erkrankungen erfüllt ist.Current approaches to haplotype block definition target either absent recombination events or the efficient description of genomic variation. This thesis aims to define blocks of single nucleotide polymorphisms (SNP) as areas of elevated linkage disequilibrium (LD). To this end, a new entropy-based measure for LD between multiple markers/loci, the Normalized Entropy Difference, is developed and is characterized as a multilocus extension of the pairwise measure r2. A corresponding algorithm for the block definition is proposed. Its evaluation on a data set of human chromosome 12 from the International Haplotype Map project proves the usefulness of the derived blocks with respect to several features, including their chromosomal coverage and the number and portion of common block haplotypes. The critical role of the SNP density for detectable LD and block structure is demonstrated. The success of association studies in common diseases with block haplotypes serving as multi-allelic markers will depend on whether the Common Variants/Common Diseases (CV/CD) hypothesis holds true for those diseases.
26
Curk, Franck. "Organisation du complexe d’espèce et décryptage des structures des génomes en mosaïque interspécifiques chez les agrumes cultivés". Thesis, Montpellier 2, 2014. http://www.theses.fr/2014MON20223/document.
Testo completoAbstract (sommario):
Les études préexistantes identifient quatre taxons de base (C. reticulata les mandariniers, C. maxima les pamplemoussiers, C. medica les cédratiers et C. micrantha) à l'origine de l'ensemble des formes cultivées suite à des événements de réticulations. Il en résulte des structures génotypiques complexes, généralement fixées par l'apomixie, fortement hétérozygotes et formées d'une mosaïque de grands fragments chromosomiques d'origines phylogénétiques différentes. La structuration de la variabilité phénotypique suggère que la différenciation initiale des taxons ancestraux est à l'origine d'une part importante de la variabilité utile des agrumes. La connaissance de l'origine des formes cultivées et de leurs structures phylogénomiques est donc indispensable à la bonne gestion des collections et à l'optimisation des programmes d'amélioration génétique. A cette fin, cette thèse explore différentes approches d'analyse de la diversité des génomes. Elle a bénéficié de l'évolution rapide des NGS et propose une utilisation raisonnée des outils disponibles en fonction des questions de recherches. Une analyse plus poussée a été conduite sur les limettiers et citronniers. Le pyroséquençage 454 (Roche) d'amplicons a été utilisé pour décrypter la structure en mosaïque interspécifique du chromosome 2 de 50 variétés à partir d'une information haplotypique multiloci et pour identifier des marqueurs diagnostiques des taxons ancestraux. Ces marqueurs ont permis, en association avec des SSR et indels, d'apporter un nouvel éclairage sur l'origine des limettiers et citronniers, par un génotypage exhaustif des collections Inra/Cirad et Ivia. Enfin, les données de re-séquençage complet Illumina de sept variétés de limettiers et de citronniers comparées à celles de représentants des taxons ancestraux nous ont permis de reconstituer la structure interspécifique de leurs génomes et de schématiser leurs caryotypes phylogénomiques. Les différentes approches ont conduit à des conclusions convergentes. Nos résultats confirment les hypothèses concernant la séquence évolutive à l'origine des bigaradiers (C. aurantium), des orangers (C. sinensis) et des pomelos (C. paradisi) à partir des pools géniques de C. maxima et C. reticulata. Ils mettent en évidence de fréquentes introgressions de C. maxima dans le génome de mandariniers considérées comme représentatifs de C. reticulata. Les contributions relatives de ces deux taxons ancestraux aux génomes de nombreuses variétés de petits agrumes (mandariniers, tangors et tangelos) ont pu être estimées. Les limettiers et citronniers résultent de multiples évènements de réticulation et C. medica est identifié comme parent mâle de la majorité des variétés diploïdes. Deux grands groupes de citronniers, sont différenciés, ceux issus d'hybridations directes C. reticulata × C. medica et ceux impliquant trois taxons ancestraux (C. maxima, C. reticulata et C. medica). Le bigaradier serait le parent femelle à l'origine des citronniers type Lisbonne (C. limon). Les limettiers de type Mexicain (C. aurantifolia) seraient issus d'une hybridation directe C. micrantha × C. medica. Enfin, les limes à gros fruits, triploïdes, ont deux origines. Les types Tahiti résulteraient probablement de la fécondation d'un ovule de citronnier type Lisbonne par un gamète diploïde de limettier type Mexicain. L'autre grand type serait issu d'un backcross entre C. aurantifolia (gamète diploïde) et C. medica. Ces connaissances sur la structure génomique des espèces secondaires permettent d'envisager une reconstruction d'idéotypes à partir du germplasm des taxons ancestraux. Elles ouvrent également la voie à des études de génétique d'association s'appuyant sur la phylogénomique des gènes impliqués dans l'élaboration des caractères de qualité, de résistance et d'adaptation. Enfin, les marqueurs diagnostiques d'espèces développés trouveront de nombreuses applications pour la caractérisation des collections et diverses études de génétiquesCitrus fruit, the most important fruit crop in the world, show a wide phenotypic diversity. Previous studies (molecular markers) identified four ancestral taxa (Citrus reticulata Blanco, mandarins; C. maxima (Burm.) Merr., pummelos; C. medica L., citrons; C. micrantha Wester, papedas) as the ancestors of all cultivated Citrus after reticulate evolutions. As a result, modern citrus varieties have complex and highly heterozygous genotypic structures, generally fixed by apomixis, and formed by a mosaic of large chromosomal fragments of different phylogenetic origins. Furthermore, the structuration of the phenotypic variability suggests that the initial differentiation of the basic taxa is the main source of most of the variability of the useful citrus phenotypic diversity. A thorough knowledge of the origin of cultivated citrus and their phylogenomic structure are essential for the management of biological resources and breeding program optimization. This thesis explores different approaches for analyzing genome diversity in order to identify the phylogenetic origins of the various horticultural citrus groups and to decipher their phylogenomic genome's structures. We focused on limes and lemons. This thesis takes advantage of the rapid evolution of NGS and proposes a rational use of available tools, based on research questions. Roche 454 parallel sequencing of amplicons provides multi-loci haplotype information on 500 base fragments. It was used to decipher the interspecific mosaic structure of chromosome 2 for fifty varieties and to identify ancestral taxa diagnostic SNP markers. The genotyping of all limes and lemons of the Inra/Cirad and Ivia germplasms with these markers, in association with SSR and indel markers, allowed to propose new hypothesis on the origins of limes and lemons. Data from Illumina whole genome re-sequencing of 7 varieties of limes and lemons, compared to those of representatives of the ancestral taxa, allowed to infer the interspecific structure of their genomes and to map out, for the first time, their phylogenomic karyotypes. The different approaches led to similar conclusions. Our results confirm previous hypothesis about the evolutionary steps at the origin of sour orange (C. aurantium), sweet orange (C. sinensis) and grapefruit (C. paradisi) involving C. maxima and C. reticulata gene pools. They highlight frequent introgressions of C. maxima in the genome of mandarin varieties despite the fact they were considered as representative of C. reticulata. We were also able to quantify the relative proportions of these two ancestral taxa in the genome of many varieties of small citrus fruit (mandarin hybrids, tangors and tangelos). Our work on limes and lemons demonstrate that C. medica is the male parent of this varietal group at the diploid level. Two groups of lemons are clearly differentiated: one from direct hybridizations between C. reticulata and C. medica, and one from crosses between hybrids (C. maxima × C. reticulata) and C. medica. Sour orange seems to be the female parent of ‘Eureka' type lemons (C. limon). The ‘Mexican' limes (C. aurantifolia) seems to come from a direct hybridization C. micrantha × C. medica. Finally, triploid big fruit limes have two major origins. The ‘Tahiti' type probably results from an ‘Eureka' type lemon (C. limon) ovule fecundated by a diploid gamete of a ‘Mexican' type lime (C. aurantifolia), while the other type would come from a back-cross between C. aurantifolia (diploid gamete) and C. medica. This new insights in genomic structure of secondary species makes to consider possible a reconstruction of these ideotypes from ancestral taxa germplasm. They also open new ways for association genetic studies based on phylogenomics of genes involved in the development of quality, resistance and adaptation traits. Finally, developed specific taxa diagnostic markers will find many applications for the characterization of collections and further genetic studies
27
Mathers, H. M. C. "Assessment of MHC haplotype in early-onset inflammatory bowel disease". Thesis, Queen's University Belfast, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.419507.
Testo completo
28
Sazonova, Nadezhda A. "Parsimony-based genetic algorithm for haplotype resolution and block partitioning". Morgantown, W. Va. : [West Virginia University Libraries], 2007. https://eidr.wvu.edu/etd/documentdata.eTD?documentid=5499.
Testo completoAbstract (sommario):
Thesis (Ph. D.)--West Virginia University, 2007.Title from document title page. Document formatted into pages; contains xi, 127 p. : ill. Includes abstract. Includes bibliographical references (p. 109-114).
29
Dai, Yu. "Genetic association studies : exploiting SNP-haplotype selection and covariate independence /". Thesis, Connect to this title online; UW restricted, 2007. http://hdl.handle.net/1773/9582.
Testo completo
30
Moeinzadeh, Mohammadhossein [Verfasser]. "De novo and haplotype assembly of polyploid genomes / Mohammadhossein Moeinzadeh". Berlin : Freie Universität Berlin, 2019. http://d-nb.info/1189660237/34.
Testo completo
31
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.
Testo completo
32
Sheffi, Jonathan 1981. "An HMM-based boundary-flexible model of human haplotype variation". Thesis, Massachusetts Institute of Technology, 2004. http://hdl.handle.net/1721.1/17993.
Testo completoAbstract (sommario):
Thesis (M. Eng.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2004.Includes bibliographical references (p. 71-77).
The construction of a meaningful and detailed description of haplotype variation holds the promise for more powerful genetic association studies. The segmentation of the human genome into blocks of limited haplotype diversity has been successfully employed by models that describe common variation. Some computational models of haplotype variation are flawed, however: they arbitrarily sever all haplotypes at block boundaries and assume that block boundaries are areas of free recombination. In reality, haplotypes break up when they recombine, and many past recombination events are predicted to occur at sites of occasional recombination. Thus, the genuine unit of shared genetic variation should often cross block boundaries, or sometimes end between them. This work seeks the truer mosaic structure of human haplotypes through flexible haplotype boundaries. This thesis introduces an HMM-based boundary-flexible model, and proves that this model is superior to a blockwise description via the Minimum Description Length (MDL) criterion.
by Jonathan Sheffi.
M.Eng.
33
Ofori-Acquah, Solomon Fiifi. "Molecular basis for CIS regulation of fetal haemoglobin expression in sickle cell disease". Thesis, King's College London (University of London), 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.324882.
Testo completo
34
Patel, Rajen. "The effects of Ly49 haplotype divergence on natural killer cell function". Thesis, University of Ottawa (Canada), 2010. http://hdl.handle.net/10393/28817.
Testo completoAbstract (sommario):
Natural killer (NK) cells target virally infected cells and tumor cells through Ly49 receptors that recognize MHC-I molecules. Different inbred mouse strains possess disparate Ly49 receptor haplotypes, in addition to NK cell activity. C5781/6 mice express less Ly49 receptors than 129S1 mice, but have a more robust NK cell population. We intend to determine if the differences in NK cell activity between these inbred mice strains are due to the differences in Ly49 receptor haplotypes. C578116 mice with the Ly49 gene cluster of 129S1 origin were generated in order to compare 129S1 and 86 Ly49 contribution to NK cell function. These B6-Ly49129 congenic mice were confirmed to express the 129 Ly49 receptor pattern by flow cytometry. NK cell activity was assessed by cytotoxicity assays using a panel of NK-resistant and NK-susceptible tumor cell lines, the ability to clear infection with murine cytomegalovirus (MCMV) as well as the ability to reject MHC-I-deficient splenocytes in vivo. Susceptibility to MCMV infection by congenic mice was similar to 129 mice. However, there was a significant increase in rejection of MHC-I-deficient cells by the congenic mice in comparison to both the 86 and 129 mice. In addition, in vitro tumor cell killing by congenic NK cells was comparable to 86. The current results indicate that expression of an increased number of Ly49 receptors promotes better education of NK cells, which in turn leads to higher rejection of MHC deficient target cells.
35
McGee, Kate. "Evolutionary Factors Shaping Haplotype and Nucleotide Diversity in Humans and Malaria". NCSU, 2008. http://www.lib.ncsu.edu/theses/available/etd-01102008-104027/.
Testo completoAbstract (sommario):
Cheaper and more rapid DNA sequencing has led to the accumulation of large amounts of genetic data and has fueled the development of new methods to analyze this data. Using population genetics theory and computational methods we can explore the evolutionary forces that shape genetic variation within and among populations of humans and malaria parasites. Demographic events such as population size change influence current patterns of genetic variation. Accounting for the demographic history of a population is critical in the interpretation of population genetic analyses, particularly in detecting of regions under selection and in making inferences about linkage disequilibrium. Characterizing how recombination rates evolve is critical for the efficient design of association studies and, in turn, the understanding of the genetics behind complex phenotypes. In malaria parasites, recombination is a key element in the creation of a wide array of antigens, which help invade host cells. We examine patterns of genetic variation in humans and malaria and explore how demographic history and recombination rates affect these patterns.
36
Haydar, Sara. "Rôle des aminoacides ramifiés dans le déterminisme génétique de la résistance à l’insuline". Thesis, Montpellier, 2018. http://www.theses.fr/2018MONTT054.
Testo completoAbstract (sommario):
La résistance à l’insuline (RI) est un processus biologique fondamental impliqué dans la plupart des maladies complexes avec un important impact dans la mortalité des populations humaines et qui reconnaît une composante génétique en interaction avec les facteurs nutritionnels. Les aminoacides ramifiés (BCAA) sont des composantes essentielles de notre diète et ont été reconnus comme de nouveaux acteurs dans la pathogénie de l’obésité et du diabète sucré soit comme des bio-marqueurs soit comme des régulateurs au niveau périphérique ou dans le système nerveux central. Ce travail a été proposé dans le cadre du projet Européen MEDIGENE (FP7-279171) visant le syndrome métabolique dans les populations Méditerranéennes. Dans ce contexte, nous avons utilisé une approche génétique combinant les SNP (single nucleotide polymorphism) et la cartographie dense des haplotypes. Nous avons mis en évidence de nouveaux gènes dans les phases tardives du catabolisme des BCAA, bien que le signal d’association ait été en relation complexe avec les taux plasmatiques de BCAA et la mesure in vivo de la RI. Dans une approche similaire, nous avons identifié sur le chromosome 4p14 un nouveau locus en relation avec la RI et le système de récompense cérébral impliquant le fibroblast growth factor (FGF) 21. Ces données ont soulevé l’intérêt pour une estimation rapide et efficace de l’apport en BCAA dans la diète nous emmenant à développer une nouvelle base de données du contenu des aliments en BCAA. Cette base est intégrée dans un nouveau logiciel pour le recueil des enquêtes alimentaires (rappels de 24h) et qui pourra être utilisée par des praticiens d’une manière sécurisée dans les pays de la Méditerranée, ouvrant ainsi de nouvelles perspectives en nutrigénomiqueInsulin resistance (IR) is a fundamental biological process involved in majority of complex disorders with high impact on mortality of human populations and with a strong genetic component in interaction with nutritional factors. Branched chain amino acids (BCAA) are essential components of human diet and recognized as new actors in pathogenesis of obesity and diabetes mellitus either as biomarkers or regulators at the peripheral systemic and nervous system. This work was proposed in the frame of the European project MEDIGENE (FP7-279171) studying the metabolic syndrome in several Mediterranean populations. In this context, we have used a genetic approach combining SNP (single nucleotide polymorphism) and fine scale haplotype mapping. We identified new genes in the later steps of BCAA catabolism responsible for IR, albeit displaying a complex signal in relation with BCAA plasma levels and in vivo IR measured by minimal model. With a similar approach, we identified equally a new locus of Chromosome 4p14 for IR in cooperation with the cerebral rewarding system involving fibroblast growth factor (FGF) 21 regulation. These data roused particular interest in estimating BCAA intake leading to the development of a novel database of BCAA content in food. This database is embedded in a new computer program for collecting dietary records (24HDR) and can be used securely by practitioners around Mediterranean countries and opening new perspectives in the nutrigenomic field
37
Delaneau, Olivier. "Développement de logiciels d'halotypage et applications". Paris, CNAM, 2008. http://www.theses.fr/2008CNAM0626.
Testo completoAbstract (sommario):
Les récentes avancées faites dans les techniques de biologie moléculaire ont mis à disposition de la communauté scientifique une grande quantité de marqueurs génétiques pouvant être analysés pour rechercher des facteurs génétiques de risque pour des maladies. A l’heure actuelle, ces techniques fournissent les génotypes, c'est-à-dire les allèles présents à chacun des marqueurs, mais elles ne permettent toujours pas d’obtenir les haplotypes, c'est-à-dire les combinaisons d’allèles de ces marqueurs que l’on retrouve sur le même chromosome. Or l’utilisation des haplotypes permet de prendre en compte simultanément l’information de plusieurs marqueurs dans l’analyse, ce qui s���avère très utile, notamment dans le cas des maladies communes. Pour cela, plusieurs méthodes de détermination « in silico » des haplotypes ont été développées depuis les années 90, dont des méthodes statistiques qui permettent d’obtenir robustement les haplotypes à partir des génotypes. Elles restent malheureusement sujettes à une complexité algorithmique qui s’avère souvent exponentielle avec le nombre de marqueurs traités. Pour surmonter ce problème de complexité et de temps de calcul, nous avons adapté plusieurs de ces méthodes d’inférence statistique à des représentations arborescentes des espaces possibles de reconstructions d’haplotypes. Nous avons notamment développé un algorithme EM et un algorithme pour modèle de Markov caché qui tirent profit de cette représentation sous forme d’arbre, en explorant uniquement les branches suffisamment probables, brisant ainsi l’aspect exponentiel du problème. Ces deux méthodes ont été implémentées respectivement dans les logiciels Ishape et ShapeIT. Nous avons ensuite comparé extensivement ces deux logiciels avec ceux utilisés jusqu’à présent par la communauté. Les résultats nous ont montré que ces deux logiciels permettaient d’obtenir une robustesse identique des haplotypes reconstruits, tout en réduisant les temps de calcul de façon significative. Ils permettent notamment d’appliquer le modèle statistique le plus efficace sur une masse de données qui lui était inaccessible jusqu’à présent. Ils trouvent donc une utilité toute particulière à l’heure où plusieurs centaines de milliers de marqueurs sont disponibles à moindre coût. De manière intéressante, la technique d’implémentation par arborescence des calculs de modèles de Markov cachés développée dans Shape-IT doit pouvoir s’appliquer à des domaines autres que la bioinformatique tels que la physique ou la financeThe recent advances in molecular biology have given access to a large amount of genetic markers, which can be associated with various disease phenotypes in order to discover the molecular etiology of common diseases. These techniques provide genotypes which are the alleles observed for each marker on chomosomes, but not the haplotypes which are the allele combinations on the same chromosome. The use of haplotypes allows to take into account simultaneously the information carried by several markers and this is very useful biology-wise. Haplotypes can be computed from the genotype data in a given population and since 1990, several methods “in silico” of inference of haplotypes have been developed, notably the statistical methods which have shown the best accuracy. Unfortunately, the methods developed still required computations with an exponential complexity with the number of markers. To avoid this, we have adapted several methods of statistical haplotype inference to use tree representations of the possible haplotype space. We have notably developed an EM algorithm and a hidden Markov model algorithm working with tree representations which permit to explore only the most probable branches of the tree in order to break the exponential complexity. These two methods were implemented respectively in the software packages Ishape and ShapeIT. We have extensively compared these two software to the haplotyping software most widely used by the community. The results show that these two software yielded an excellent accuracy while reducing strongly the running times. They thus represent a huge improvement in the context of the hundreds of thousands genetic markers available today
38
Dias, Alves Thomas. "Modélisation du déséquilibre de liaison en génomique des populations par méthodes d'optimisation". Thesis, Université Grenoble Alpes (ComUE), 2017. http://www.theses.fr/2017GREAS052/document.
Testo completoAbstract (sommario):
Nous présentons un nouveau formalisme et des nouvelles méthodes pour modéliser le déséquilibre de liaison et tenir compte de la structure en haplotypes pour les données issues de la génomique des populations. La modélisation repose sur un problème d'optimisation avec contraintes qui est résolue avec un algorithme de programmation dynamique. Les méthodes établies ont toutes l'avantage d'avoir un coût algorithmique linéaire et donc de pouvoir traiter de grands jeux de données.Dans un premier temps, nous avons appliqué notre approche à l'étude des populations métisses et plus particulièrement au problème d'inférence des coefficients de métissage locaux.Notre méthode a été appliquée à des génotypes simulés de métissage humain ainsi qu'à des vrais génotypes obtenus dans des populations métisses de peupliers.Dans un second temps, nous avons développé notre formalisme d'optimisation pour traiter de l'inférence des haplotypes à partir des génotypes d'une population.L'ensemble de ces méthodes d'optimisation a été développé dans un module Python qui s'appelle LoterWe present a new formalism and new methods to model linkage disequilibrium and to account for haplotype structure of population genomics data. Modeling relies on an optimization problem with constraints that is solved using dynamic programming. The algorithmic cost of proposed methods is linear, which is a desirable property to process large datasets.First, we applied our framework to study admixed populations and perform local ancestry inference. Our method is applied to simulated genotypes of admixed human populations and to real genotypes from admixed Populus species.Second, we developed our optimization framework to perform haploptype phasing and imputation based on a population of genotypes. All optimization methods have been developed in a Python package called Loter
39
Mwema, Hadija Saidi. "Forensic identification of six of Tanzanian populations using the extended haplotype markers". Thesis, University of the Western Cape, 2011. http://etd.uwc.ac.za/index.php?module=etd&action=viewtitle&id=gen8Srv25Nme4_2349_1325671867.
Testo completoAbstract (sommario):
The aim of the present study was to evaluate the power of discrimination and genetic (diversity) parameters in the Y chromosome extended haploytpe markers in populations of Tanzania for forensic and populations studies. Eleven Y chromosome extended haplotype markers were selected for this study, these includes Minimal haplotypes markers i.e. DYS19, DYS390, DYS391, DYS392, DYS393, DYS385a/b, DYS389I/II and two additional markers DYS438 and DYS439. Six populations of Tanzania were investigated under this study. These populations were selected based on the language family categoriesNiger Congo (Kuria and Sukuma), Nilo Saharan (Luo and Maasai) and Afro Asiatic (Iraqw and Alagwa).
40
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.
Testo completoAbstract (sommario):
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).eSSENCE
41
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.
Testo completoAbstract (sommario):
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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Taylor, Aimee Rebecca. "Estimation of Plasmodium falciparum allele and multi-SNP haplotype and genotype frequencies". Thesis, University of Oxford, 2016. https://ora.ox.ac.uk/objects/uuid:c192e7cb-b6e0-4e23-a880-de46d668ef07.
Testo completoAbstract (sommario):
Malaria kills hundreds of thousands of people each year, yet is entirely curable given prompt treatment. Malaria parasites evolve resistance to antimalarial drugs, hence routine surveillance of antimalarial resistance is vital. The surveillance of parasite genetic markers of resistance provides an economical adjunct to clinical efficacy trials, and has the potential to resolve drug specific resistance ahead of clinical failure. To monitor spatiotemporal changes using genetic markers, frequencies of alleles and/or haplotypes and genotypes spanning multiple single nucleotide polymorphisms (SNPs) are required. However, multiclonal infections complicate frequency estimation, especially in highly endemic regions. With the aim of harnessing the full potential of genetic markers for the surveillance of antimalarial resistance, a statistical model to estimate frequencies is proposed. The model builds upon existing methods (reviewed in chapter 2), without reliance upon experimentally-derived estimates of the sample-wise multiplicities of infection (MOIs). Its ability to generate precise and accurate estimates within a Bayesian framework is documented in chapter 3. In chapter 4, the model is applied to data collected from a cohort of children enrolled in a longitudinal trial in Uganda, generating valuable insight into haplotype frequency trends. In chapter 5, the model is extended to investigate inter-child variability in the aforesaid cohort, revealing a small amount of inter-child variation. In chapter 6, the model is modified to enable the analysis of short-read sequencing data, with application to data from malaria patients in Northern Ghana, providing insight into the extent of within-host diversity and anti-folate resistance in the region. In summary, this thesis documents the development, application, extension and modification of a model designed to estimate population-level frequencies of P. falciparum alleles and multi-SNP haplotypes and genotypes within a Bayesian framework. It is hoped that the model and its proposed framework will provide a practical tool for surveillance of antimalarial resistance, as well as a foundation on which to develop further methods.
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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.
Testo completoAbstract (sommario):
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.
Testo completo
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Caffrey, Tara M. "Functional effects of haplotype-specific sequence variation at the human MAPT locus". Thesis, University of Oxford, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.525267.
Testo completo
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Fletcher, Benjamin. "Haplotype diversity at the CYP2D6 locus : human demography, evolution and disease susceptibility". Thesis, University College London (University of London), 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.404668.
Testo completo
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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.
Testo completoAbstract (sommario):
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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Knudsen, Gabriel Arther. "Investigating complex phenotypes: haplotype association mapping benzene pharmacokinetics in isogenic mouse strains". Diss., The University of Arizona, 2011. http://hdl.handle.net/10150/202998.
Testo completoAbstract (sommario):
A role for gene variants in regulating the pharmacokinetics of systemically available toxicants has not yet been established. A panel of 18 genetically-diverse inbred mouse strains was used to determine the range of total exposure kinetic parameters in blood and bone marrow following a single oral administration of benzene (100 μg/kg) to male and female mice. Large ranges in several pharmacokinetic parameters were found when data from blood and bone marrow were analyzed. AUC and CL_F pharmacokinetic parameters in blood and bone marrow pharmacokinetics were strikingly different as were these parameters in males and females. Final clearance (CL_F) was found to be the most statistically robust pharmacokinetic parameter as it accounted for exposure of the matrix (AUC) and normalized for dose variations among the strains. The CL_F values in blood and bone marrow used for haplotype association mapping showed 331 and 164 quantitative trait loci with statistical significance, respectively (male mice; -logP>4). Two loci were found to be shared between males and females QTL bone marrow data sets and one common locus was found for male blood and bone marrow data. No overlap was found among blood QTL in males and females (or between blood and bone marrow data from females). Protein and mRNA expression data for the primary benzene-metabolizing enzymes CYP2E1 and UGT1A6 showed very little strain-dependent variation. Strain dependent differences in mRNA levels of NQO1 and MPO were small but statistically significant, as were those for GAPDH and β2-microglobulin. These data demonstrated that polymorphisms with the greatest contribution toward overall variations in systemic exposures occurred in genes encoding for non-metabolic proteins. While exposure does not equate to toxicity, identification of the genes regulating distribution and clearance may be useful for investigating host susceptibility to toxic effects following benzene exposure. This research was supported in part by the NIEHS NTP Grant N01ES45529, NIEHS Toxicology and Toxicogenomics Training Grant (5T32ES007091-29), NIEHS/NTP Division of Intramural Research, and Southwest Environmental Science Center Grant P3ES06694.
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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.
Testo completoAbstract (sommario):
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 améliorationConsumers 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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Pezzolesi, Marcus Guy. "Novel Mechanisms Of Pten Dysfunction In Pten Hamartoma Tumor Syndromes". The Ohio State University, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=osu1205158047.
Testo completo