1,721,002 research outputs found
Function prediction of butyrophilines by the study of their evolution and their genetic variability
No full textDans le cadre de cette thèse nous nous sommes intéressés à l'étude de l'évolution et de la variabilité génétique de la famille des butyrophilines (BTN), des récepteurs de la superfamille des immunoglobulines impliqués dans la régulation de la réponse immunitaire. Par une étude phylogénétique approfondie nous avons caractérisé chez les mammifères 14 groupes phylogénétiques résultant d'une série de duplications à partir de huit gènes ancestraux à la base des thériens. Par la suite, nous avons étudié l'évolution des BTN de la région CMH chez les primates et leur variabilité génétique dans les populations humaines par une analyse minutieuse des données de séquençage générées du projet 1000 Genomes pour plus de 1600 individus à travers le monde. Nous avons montré que l'évolution du gène BTNL2 est marquée par une pression de sélection positive diversifiante chez les mammifères qui est accompagnée chez les hominoïdes d'un niveau de polymorphisme élevé induisant la formation de variants tronqués de BTNL2. Chez l'homme, quatre lignages d'allèles ont été identifiés. Ils ont été maintenus à des fréquences intermédiaires par une forte sélection balancée. D'autre part, l'analyse phylogénétique détaillée du groupe BTN3 (BTN3A1, 3A2 et 3A3) a montré la présence d'une évolution concertée, caractérisée par une homogénéisation forte et récurrente de la région codant pour le peptide signale et le domaine IgV chez les hominoïdes, au cours de laquelle les séquences de 3A1 et 3A3 sont remplacées par la séquence de 3A2. Chez l'homme, ces gènes sont polymorphismes important avec plus de 46 allèles chacun, mais avec la présence d'une homogénéisation extrême des séquences du domaine IgVIn this thesis we were interested in studying the evolution and the genetic variability of the butyrophilin family (BTN), a family of immune receptors belonging to the immunoglobulin superfamily implicated in the regulation of immune response. Through a thorough phylogenetic study of the family we characterized 14 phylogenetic groups in mammals resulting from a series of duplications from eight ancestral genes at the base of therian. Thereafter, we studied the evolution of the BTN of the MHC region and their genetic variability in human populations by a careful analysis of sequencing data generated by the consortium 1000 Genomes for more than 1,600 individuals representing 26 populations worldwide. We have shown that the evolution of BTNL2 gene is marked by a positive diversifying selection in placental mammals. This selection pressure is accompanied in hominoids of a high level of polymorphism inducing the formation of truncated BTNL2 variants. In humans this high level of polymorphism results in the presence of four ancient allele lineages that are maintained at intermediate frequencies by a strong balancing selection. On the other hand, a detailed phylogenetic analysis of BTN3 group (BTN3A1, 3A2 and 3A3) showed that these genes evolve in hominoids in a concerted manner characterized by a strong and recurrent homogenization of the regions encoding for the peptide signal and the IgV domain in which the 3A1 and 3A3 sequences are replaced by the 3A2 sequence. In humans these genes are polymorphic with over 46 alleles each, but with the presence of extreme homogenization of IgV domain sequence
Finding novel gene candidates and polymorphisms involved in host-pathogen interactions
No full textLa coévolution ainsi que les différentes interactions entre hôte et pathogène contribuent à former la diversité génétique de ces deux organismes. Dans le cadre de cette thèse, nous nous sommes intéressés à l’étude de la variabilité génétique de 1760 gènes immunitaires choisis suivant des critères définis, pour essayer d’expliquer pourquoi il existe une variation individuelle face aux infections. L’objectif principal de ce projet était alors de caractériser et d'analyser de nouveaux gènes et polymorphismes immunitaires pouvant expliquer le contrôle ou la susceptibilité à certaines infections. Deux études pilotes nous ont permis de développer le pipeline de détection de polymorphismes. Pour la première, le polymorphisme des 3 gènes CD28, CTLA4, et ICOS a été caractérisé. Dans la deuxième, nous avons caractérisé le polymorphisme de 10 gènes impliqués dans la réponse immunitaire contre M. tuberculosis. Ces gènes ne sont pas très polymorphes et trois d’entre eux sont très conservés. Ces deux études nous ont aidés à préparer l’analyse à grande échelle avec les mises au point et l’amélioration du pipeline. Nous avons sélectionné 1760 gènes en se basant sur des critères définis. La variabilité génétique a été étudiée dans les populations humaines par une analyse minutieuse in silico de données de séquençage d’exomes générées par différents projets et consortiums pour plus de 700 individus représentant 20 populations à travers le monde. 30 gènes les plus polymorphes ont été ainsi identifiés. Ces gènes pourront être entièrement caractérisés et les données produites pourraient être comparées avec des données de résistance/sensibilité de certaines maladies infectieuses.Host-pathogen co-evolution and interactions contribute in shaping the genetic diversity of both organisms. The objective of this thesis is to define the genetic basis of variability in disease resistance/susceptibility through the development of large-scale in silico screens to identify novel gene candidates implicated in host-pathogen interactions (such as tuberculosis).A pilot study was conducted on CD28, CTLA4, and ICOS to investigate their polymorphism. As a first step in our study based on data available in the literature, we selected a set of ten genes relevant for the immune response against M. tuberculosis. Seven of these genes were moderately polymorphic, while three of them were highly conserved. This analysis was used to prepare and setup the large scale analysis using the same developed pipeline for polymorphism detection and allele reconstruction. For our in silico, we used sequence data from several projects and consortiums to isolate most polymorphic human genes amongst a list of over 1760 candidates selected based on already established relevance for infections and on evolutionary considerations. A first screen of 64 individuals from eight different populations from several regions of the world was performed and most variable genes were selected for further extensive analyses on a larger panel (715 individuals). 30 most polymorphic genes were thus identified. The extent of polymorphism and the allelic worldwide variants of each of these 30 genes are ready to be fully characterized. The data generated could be compared against infectious disease resistance/susceptibility data to identify potentially relevant gene variation
The MHC big bang : duplication and exons shuffling during the chordate evolution. An hypothetico-deductive approach
No full textMise en place du génome des vertébrés (le cas du complexe majeur d'histocompatibilité (CMH))
No full textAIX-MARSEILLE2-BU Sci.Luminy (130552106) / SudocSudocFranceF
The MHC big bang : duplication and exons shuffling during the chordate evolution. An hypothetico-deductive approach
No full textPaleogenetics and Past Infections: the Two Faces of the Coin of Human ă Immune Evolution
No full textInternational audienceWith the advent of next-generation sequencing, paleogenetics has ă considerably expanded over the past few years and notably encompassed ă the characterization of the genomes of archaic humans who lived more ă than 30,000 years ago. These paleogenetics investigations have revealed ă that admixture between modern and archaic humans occurred, with ă Neanderthals having contributed to 1.5% to 2.1% of modern Eurasian ă genomes, and Denisovans to 3% to 6% of modern Melanesian genomes and ă to approximately 0.2% of modern Asian genomes. Although these ă contributions are modest, they played a major role in shaping immune ă gene families, such as the HLA class I genes, for which the archaic ă alleles now represent more than 50% of the alleles in Europe and Asia. ă Such a high frequency is consistent with these archaic HLA class I ă variants having been positively selected because of their protective ă effect against contagious and devastating epidemics, such as those due ă to the plague agent Yersinia pestis or to Mycobacterium tuberculosis, ă which is responsible for deadly tuberculosis. While the exact nature of ă the infectious agents that contributed to the selection of the archaic ă variants is unknown, we are entering an exciting period in which ă paleogenetics and paleomicrobiology data can be integrated to generate a ă clearer picture of how the immune system of modern populations was ă shaped and the role admixture and epidemics have played in such ă evolutions
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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