Résumé : Ce travail de thèse intitulé «Evaluation de marqueurs génétiques du complexe Mycobacterium tuberculosis combinée à l'utilisation d'outils bioinformatiques: apport en épidémiologie et phylogénie de la tuberculose» a consisté en la sélection et l'évaluation de marqueurs minisatellites dans le cadre d'études épidémiologiques et phylogénétiques du bacille tuberculeux, Une première partie a ainsi porté sur l'épidémie de tuberculose en Guadeloupe, Martinique, et Guyane française ainsi que dans un pays continental à faible incidence de tuberculose, la Suède, Les résultats montrent les disparités existant entre les populations de patients tuberculeux des 3 départements français d'Amérique (DFA) ainsi que les similitudes génotypiques existant entre les bacilles tuberculeux. Par ailleurs le rôle majeur joué par les cas d'importation dans l'épidémie de tuberculose a été montré aussi bien dans les DFA qu'en Suède. Nous nous sommes ensuite intéressés à une utilisation optimale des minisatellites pour une meilleure discrimination de la famille génotypique émergeante « Beijing» circulant au Japon (Osaka, Kobe et Okinawa), ainsi qu'en Russie. Nous avons constaté le faible pouvoir discriminant du format classique 12-locus MIRU (Mycobacterial lnterspersed Repetitive Units) et proposons plusieurs nouvelles stratégies de typage basées plusieurs marqueurs minisatellites incluant certains locus hypervariables. Enfin, dans un troisième volet, nous avons étudié la diversité génétique des bacilles tuberculeux circulant actuellement dans la Caraïbe. laquelle semble refléter le passé historique très particulier de cette zone géographique au croisement d'une multitude de peuplements.
This thesis entitled "Evaluation of genetic markers of Mycobacterium tuberculosis combined with the use of bioinformatics tools: input for epidemiology and phylogeny of tuberculosis" deals with the selection and evaluation of minisatellite markers in the context of epidemiological and phylogenetic studies of the tubercle bacillus M. tuberculosis. The first part of the present work has focused on the epidemic of tuberculosis in Guadeloupe, Martinique and French Guiana as well as in a low incidence continental country, i.e Sweden. The results show differences between populations of TB patients in the three French Departments of America and similarities between the genotypes of the circulating tubercle bacilli Moreover, results highlight the important role played by imported cases for TB epidemic the three French departments of America and Sweden. ln a second part, minisatellite markers have been evaluated for a better discrimination of strains of the emerging genotype "Beijing" circulating in Japan (Osaka, Kobe and Okinawa), and Russia. A low discriminatory power of classical format 12-locus MIRU (Mycobacterial lnterspersed Repetitive Units) was observed and new combinations of minisatellites have also been proposed including hypervariable locus. Finally, the genetic diversity of tubercle bacilli circulating in the Caribbean was investigated which currently seem to reflect historical past of this very special region at the intersection of a multitude of cultures and peoples.

http://www.theses.fr/2011AGUY0427/document

Éditeur(s) : HAL CCSD Royal Society, The
Résumé : International audience
Determining the conditions under which populations may persist requires accurate estimates of demographic parameters, including immigration, local reproductive success, and mortality rates. In marine populations, empirical estimates of these parameters are rare, due at least in part to the pelagic dispersal stage common to most marine organisms. Here, we evaluate population persistence and turnover for a population of orange clownfish, Amphiprion percula, at Kimbe Island in Papua New Guinea. All fish in the population were sampled and genotyped on five occasions at 2-year intervals spanning eight years. The genetic data enabled estimates of reproductive success retained in the same population (reproductive success to self-recruitment), reproductive success exported to other subpopulations (reproductive success to local connectivity), and immigration and mortality rates of sub-adults and adults. Approximately 50% of the recruits were assigned to parents from the Kimbe Island population and this was stable through the sampling period. Stability in the proportion of local and immigrant settlers is likely due to: low annual mortality rates and stable egg production rates, and the short larval stages and sensory capacities of reef fish larvae. Biannual mortality rates ranged from 0.09 to 0.55 and varied significantly spatially. We used these data to parametrize a model that estimated the probability of the Kimbe Island population persisting in the absence of immigration. The Kimbe Island population was found to persist without significant immigration. Model results suggest the island population persists because the largest of the subpopulations are maintained due to having low mortality and high self-recruitment rates. Our results enable managers to appropriately target and scale actions to maximize persistence likelihood as disturbance frequencies increase.
ISSN: 0962-8452

hal-01239322
https://hal-univ-perp.archives-ouvertes.fr/hal-01239322
DOI : 10.1098/rspb.2015.1311

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
PCR is the most widely applied technique for large scale screening of bacterial clones, mouse genotypes, virus genomes etc. A drawback of large PCR screening is that amplicon analysis is usually performed using gel electrophoresis, a step that is very labor intensive, tedious and chemical waste generating. Single genome amplification (SGA) is used to characterize the diversity and evolutionary dynamics of virus populations within infected hosts. SGA is based on the isolation of single template molecule using limiting dilution followed by nested PCR amplification and requires the analysis of hundreds of reactions per sample, making large scale SGA studies very challenging. Here we present a novel approach entitled Long Amplicon Melt Profiling (LAMP) based on the analysis of the melting profile of the PCR reactions using SYBR Green and/or EvaGreen fluorescent dyes. The LAMP method represents an attractive alternative to gel electrophoresis and enables the quick discrimination of positive reactions. We validate LAMP for SIV and HIV env-SGA, in 96- and 384-well plate formats. Because the melt profiling allows the screening of several thousands of PCR reactions in a cost-effective, rapid and robust way, we believe it will greatly facilitate any large scale PCR screening
ISSN: 1932-6203

hal-01163756
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01163756
DOI : 10.1371/journal.pone.0128188
PUBMED : 26053379

Éditeur(s) : HAL CCSD European Centre for Disease Prevention and Control
Résumé : International audience
Leishmaniasis is endemic in southern Europe, and in other European countries cases are diagnosed in travellers who have visited affected areas both within the continent and beyond. Prompt and accurate diagnosis poses a challenge in clinical practice in Europe. Different methods exist for identification of the infecting Leishmania species. Sixteen clinical laboratories in 10 European countries, plus Israel and Turkey, conducted a study to assess their genotyping performance. DNA from 21 promastigote cultures of 13 species was analysed blindly by the routinely used typing method. Five different molecular targets were used, which were analysed with PCR-based methods. Different levels of identification were achieved, and either the Leishmania subgenus, species complex, or actual species were reported. The overall error rate of strains placed in the wrong complex or species was 8.5%. Various reasons for incorrect typing were identified. The study shows there is considerable room for improvement and standardisation of Leishmania typing. The use of well validated standard operating procedures is recommended, covering testing, interpretation, and reporting guidelines. Application of the internal transcribed spacer 1 of the rDNA array should be restricted to Old World samples, while the heat-shock protein 70 gene and the mini-exon can be applied globally.
ISSN: 1560-7917

hal-01460743
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01460743
DOI : 10.2807/1560-7917.ES.2016.21.49.30418
PUBMED : 27983510

Éditeur(s) : HAL CCSD Springer Verlag
Résumé : The area of forest plantations is increasing worldwide helping to meet timber demand and protect natural forests. However, with global change, monospecific plantations are increasingly vulnerable to abiotic and biotic disturbances. As an adaption measure we need to move to plantations that are more diverse in genotypes, species, and structure, with a design underpinned by science. TreeDivNet, a global network of tree diversity experiments, responds to this need by assessing the advantages and disadvantages of mixed species plantations. The network currently consists of 18 experiments, distributed over 36 sites and five ecoregions. With plantations 1-15 years old, TreeDivNet can already provide relevant data for forest policy and management. In this paper, we highlight some early results on the carbon sequestration and pest resistance potential of more diverse plantations. Finally, suggestions are made for new, innovative experiments in understudied regions to complement the existing network.
ISSN: 0044-7447

hal-01204232
https://hal.archives-ouvertes.fr/hal-01204232
DOI : 10.1007/s13280-015-0685-1
PRODINRA : 324368
PUBMED : 26264716

Éditeur(s) : HAL CCSD Springer Verlag
Résumé : International audience
Purpose Human papillomavirus (HPV) is known to play a role in the development of head and neck squamous cell carcinomas (HNSCC) and to date, no study has reported on the association between oral HPV infection and HNSCC in the Caribbean. The objective was to determine the prevalence of oral HPV infection in the French West Indies (FWI), overall and by HPV genotype, among HNSCC cases and healthy population controls. Method We used data from a population-based case-control study conducted in the FWI. The prevalence of oral HPV was estimated separately among 100 HNSCC cases (mean age 59 years) and 308 population controls (mean age 57 years). Odds ratios (OR) and 95% confidence intervals (CI) were estimated using a logistic regression adjusting for age, sex, tobacco, and alcohol consumption, to assess the association between oral HPV infection and HNSCC. Results Prevalence of oral HPV infections was 26% in controls (30% in men and 14% in women) and 36% in HNSCC cases (36% in men, 33% in women). HPV52 was the most commonly detected genotype, in cases and in controls. The prevalence of HPV16, HPV33, and HPV51 was significantly higher in cases than in controls (p = 0.0340, p = 0.0472, and 0.0144, respectively). Oral infection with high-risk HPV was associated with an increase in risk of HNSCC (OR 1.99, 95% CI 0.95-4.15). HPV16 was only associated with oropharyngeal cancer (OR 16.01, 95% CI 1.67-153.64). Conclusion This study revealed a high prevalence of oral HPV infection in this middle-aged Afro-Caribbean population, and a specific distribution of HPV genotypes. These findings may provide insight into HNSCC etiology specific to the FWI.
ISSN: 0957-5243

hal-01659247
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01659247
DOI : 10.1007/s10552-017-0966-z
PUBMED : 28948421

Éditeur(s) : HAL CCSD Elsevier
Résumé : Over-exploitation and fragmentation are serious problems for tropical forests. Most sustainable forest management practices avoid clear-cuts and apply selective logging systems focused on a few commercial species. We applied a simulation model to estimate the impact of such selective logging scenarios on the genetic diversity and demography of four tropical tree species from French Guiana. The simulations used data on genetic and demographic composition, growth, phenology and pollen and seed dispersal obtained for Dicorynia guianensis, Sextonia rubra, Symphonia globulifera and Vouacapoua americana at the experimental site in Paracou. Whereas Symphonia globulifera serves as a model for a species with low logging pressure, the other three species represent the most exploited tree species in French Guiana. In simulations with moderate logging, typical for French Guiana, with large cutting diameter (>60 cm diameter) and long cutting cycles (65 years), the two species V. americana and Sextonia rubra were not able to recover their initial stock at the end of the rotation period, with a large decrease in the number of individuals and in basal area. Under a more intensive logging system (cutting diameter >45 cm diameter, cutting cycles of 30 years) that is common practice in the Brazilian Amazon, only Symphonia globulifera showed no negative impact. Generally, the differences between the genetic parameters in the control scenarios without logging and the logging scenarios were surprisingly small. The main reasons for this were the overlapping of generations and the effective dispersal ability of gene vectors in all species, which guarantee relative homogeneity of the genetic structure in different age classes. Nevertheless, decreasing the population size by logging reduced the number of genotypes and caused higher genetic distances between the original population and the population at the end of the logging cycles. Sensitivity analysis showed that genetic changes in the logging scenarios were principally determined by the growth, densities and cutting diameter of each species, and only to a very small extent by the reproductive system including factors such as pollen and seed dispersal and flowering phenology
ISSN: 0006-3207

hal-01032050
https://hal.archives-ouvertes.fr/hal-01032050
DOI : 10.1016/j.biocon.2006.02.014

Éditeur(s) : HAL CCSD Wiley
Résumé : Outcrossing rates, pollen dispersal and male mating success were assessed in Dicorynia guianensis Amshoff, a neotropical tree endemic to the Guiana shield. All adult trees within a continuous area of 40 ha (n = 157) were mapped, and were genotyped with six microsatellite loci. In addition, progenies were genotyped from 22 mature trees. At the population level, the species was mostly outcrossing (tm = 0.89) but there was marked variation among individuals. One tree exhibited mixed mating, confirming earlier results obtained with isozymes that D. guianensis can tolerate selfing. A Bayesian extension of the fractional paternity method was used for paternity analysis, and was compared with the neighbourhood method used widely for forest trees. Both methods indicated that pollen dispersal was only weakly related to distance between trees within the study area, and that the majority (62%) of pollen came from outside the study stand. Using maximum likelihood, male potential population size was estimated to be 1119, corresponding to a neighbourhood size of 560 hectares. Male mating success was, however, related to the diameter of the stem and to flowering intensity assessed visually. The mating behaviour of D. guianensis is a combination of long-distance pollen flow and occasional selfing. The species can still reproduce when it is extremely rare, either by selfing or by dispersing pollen at long distances. These results, together with the observation that male mating success was correlated with the size of the trees, could be implemented in management procedures aiming at regenerating the species
ISSN: 0962-1083

hal-01032227
https://hal.archives-ouvertes.fr/hal-01032227
DOI : 10.1111/j.1365-294X.2004.02127.x

Éditeur(s) : World Aquaculture Society, Aquaculture 2006
Résumé : Oysters are among the most familiar of all marine invertebrate taxa. However our knowledge of oyster phylogeny and systematics is fragmentary. This is principally due to the plastic growth patterns of these animals, which result in a wide range of overlapping, ecophenotypic variants that greatly reduce the value of analysis based on shell morphology. Besides that, many intentional or accidental anthropogenic transfers have emphasised this situation. In several cases of misclassification or misidentification of oysters, DNA molecular data, have provided valuable new insights on the tracing of introductions or more generally on the phylogeographic relationships between oyster species. We will illustrate this issue with recent case studies from our lab on several flat and cupped oysters: (1) the Crassostrea gigas – Crassostrea angulata couple of Asian species and their successive introductions in Europe, (2) the new species of cupped oysters, Crassostrea honkongensis, described in Hong-Kong and very divergent from the species Crassostrea gigas it was initially supposed to be, (3) the mangrove oyster Crassostrea gasar that was shown not only to be present along the coasts of Western Africa but also along the Atlantic coasts of South America, and (4) the geographic disjunction between Ostreola stentina, described in the Mediterranean Sea, and the genetically closely related species Ostrea aupouria (from New Zealand) and Ostreola equestris (from Mexico Gulf/Atlantic). At the intra specific level, we will focus on one of the main documented case in Europe, the flat oyster, Ostrea edulis. It is a marine bivalve whose natural geographical distribution ranges along the European Atlantic coast from Norway to Morocco, in addition to the Mediterranean and Black Sea. Studies of allozymes, microsatellites and mitochondrial differentiation over the whole range concluded that a significant divergence existed between Mediterranean and Atlantic populations, together with an isolation-by-distance pattern. However, the average mitochondrial haplotypic diversity displayed a high among populations variance, reflecting smaller effective population size in some locations. Additionally, a ten-fold quantitative difference was observed in the same study in Fst between the mitochondrial and the nuclear genomes, which could be due to sex biased differential reproductive success between males and females. In order to further document this hypothesis, two experiments at the population level were conducted. First, brooding females were sampled in a wild population and the number of males fertilizing a given female estimated. Then, parentage analyses were achieved under experimental conditions: successive mass spawnings were collected from a population of potential genitors kept in hatchery, whose genotypes were known, in order to infer a posteriori the relative contribution of each genitor. Moreover, we aimed to better understand the reproduction dynamics of this species. Several patterns of spawning could be distinguished: unique, successive or extended in time. The different parental contributions and reproductive behaviors observed in these experiments are discussed in the context of the hypothesis of a variance in the reproductive success of males and females and consequences in local and temporal reduced effective population sizes.

Droits : info:eu-repo/semantics/openAccess
http://archimer.ifremer.fr/doc/2006/acte-3475.pdf
http://archimer.ifremer.fr/doc/00000/3475/

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
BACKGROUND: Estrogens are thought to play a critical role in prostate carcinogenesis. It has been suggested that polymorphisms of genes encoding enzymes involved in estrogen metabolism are risk factors for prostate cancer. However, few studies have been performed on populations of African ancestry, which are known to have a high risk of prostate cancer.OBJECTIVE: We investigated whether functional polymorphisms of CYP17, CYP19, CYP1B1, COMT and UGT1A1 affected the risk of prostate cancer in two different populations of African ancestry.METHODS: In Guadeloupe (French West Indies), we compared 498 prostate cancer patients and 565 control subjects. In Kinshasa (Democratic Republic of Congo), 162 prostate cancer patients were compared with 144 controls. Gene polymorphisms were determined by the SNaPshot technique or short tandem repeat PCR analysis. Logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI).RESULTS: The AA genotype and the A allele of rs4680 (COMT) appeared to be inversely associated with the risk of prostate cancer in adjusted models for both Afro-Caribbean and native African men. For the A allele, a significant inverse association was observed among cases with low-grade Gleason scores and localized clinical stage, in both populations.CONCLUSIONS: These preliminary results support the hypothesis that polymorphisms of genes encoding enzymes involved in estrogen metabolism may modulate the risk of prostate cancer in populations of African ancestry.
ISSN: 1932-6203

hal-01668333
https://hal.univ-antilles.fr/hal-01668333
DOI : 10.1371/journal.pone.0153609
PUBMED : 27074016

Éditeur(s) : HAL CCSD WB Saunders
Résumé : International audience
: The apicomplexan parasite Toxoplasma gondii was discovered a little over one hundred years ago and was soon recognized as a pathogen responsible for congenital infection. But detailed understanding of its epidemiology emerged only after 1970 with the discovery of its life cycle. In the last ten years, high resolution molecular tools have allowed the characterization of various strain types with different virulence patterns, and current studies are exploring the distribution of these different genotypes. In parallel, sophisticated diagnostic tools have been developed and awareness of disease burden has led some European countries with high prevalence rates to implement screening of pregnant women. In this article, the screening options and therapies used to prevent congenital toxoplasmosis are dissected in the light of recent data from cohort studies and other epidemiological data.
ISSN: 0163-4453

hal-00875492
https://hal.archives-ouvertes.fr/hal-00875492
https://hal.archives-ouvertes.fr/hal-00875492/document
https://hal.archives-ouvertes.fr/hal-00875492/file/Robert-Gangneux_-_It_is_not_only_the_cat_that_did_it_-_how_to_prevent_and_treat_congenital_toxoplasmosis_HAL.d.pdf
DOI : 10.1016/j.jinf.2013.09.023

Éditeur(s) : HAL CCSD Saint-Maurice (Val de Marne) : Institut de veille sanitaire
Résumé : National audience
Introduction – Le nombre d’accès palustres diminue globalement en Guyane, alors que les orpailleurs travaillantsur les sites illégaux semblent particulièrement touchés par cette pathologie. Les objectifs de cette étudeétaient de déterminer la prévalence du paludisme dans cette population, les comportements associés ainsi quele niveau de résistance des parasites vis-à-vis des dérivés de l’artémisinine.Matériel et méthodes – Les inclusions ont eu lieu sur les sites de repli fréquentés par les orpailleurs le long dufleuve Maroni. Ont été effectués : un test de diagnostic rapide du paludisme, un questionnaire, un prélèvementsanguin pour PCR et un génotypage du gène pfK13 pour les PCR positives à Plasmodium falciparum.Résultats – De janvier à juin 2015, 421 orpailleurs ont été inclus, majoritairement des hommes (70,6%) brésiliens(93,8%). La prévalence du portage de plasmodies déterminée par PCR était en moyenne de 22,3%(IC95%: [18,3-26,3]), à 84% asymptomatiques. Les espèces identifiées étaient principalement P. falciparum(47,9%) puis P. vivax (37,2%), plus 10,6% de co-infections. Lors du dernier accès palustre, 52,4% des orpailleursavaient eu recours à l’automédication, majoritairement avec des dérivés de l’artémisinine (93,8%) avecune mauvaise observance (37,8%). L’analyse du gène pfK13 n’a pas mis en évidence de mutations associéesà la résistance à P. falciparumDiscussion – La prévalence élevée de porteurs asymptomatiques de plasmodies constitue un réservoir importantde transmission dans la région. L’utilisation massive de dérivés de l’artémisinine associée à une mauvaise observancedes traitements sont des facteurs de risque d’émergence de résistance imposant des mesures rapides
ISSN: 0245-7466

inserm-01491193
http://www.hal.inserm.fr/inserm-01491193
http://www.hal.inserm.fr/inserm-01491193/document
http://www.hal.inserm.fr/inserm-01491193/file/2017%2C%20Douine%20-%20Paludisme%20et%20orpaillage%20ill%C3%A9gal%20en%20Guyane.pdf

Éditeur(s) : HAL CCSD
Résumé : Mon document "Titres et travaux" contient 5 articles au format éditeur.
Mes premiers travaux de recherche, me permettant de soutenir une thèse de doctorat en décembre 1999, ont été effectués au sein du laboratoire du professeur Bernard GRANDCHAMP (unité 409 de l'INSERM) sous la direction du docteur Marie-Christine LECOMTE. Mon travail s'est intégré dans l'étude fonctionnelle et structurale de certains domaines des spectrines érythroïdes et non érythroïdes, principalement le site de tétramérisation et le domaine SH3. Concernant la tétramérisation de la spectrine érythroïde j'ai identifié les régions minimales nécessaires et suffisantes pour former le tétramère puis j'ai mis en évidence une relation entre certaines mutations de la spectrine associées à des anomalies membranaires du globule rouge et la sévérité du défaut de formation du tétramère. J'ai ensuite identifié plusieurs ligands du domaine SH3 de la spectrine non érythroïde. L'un d'entre eux m'a permis de définir une régulation de la protéolyse ciblée de cette spectrine faisant intervenir un mécanisme de phosphorylation/déphosphorylation. Ma formation initiale fut donc celle d'un biochimiste que j'ai étendue peu à peu vers la biologie moléculaire et la biologie cellulaire.
Puis, souhaitant acquérir les connaissances nécessaires au développement de modèles murins, j'ai décidé d'effectuer mon stage post-doctoral à l'Institut COCHIN (unité 567 de l'INSERM) dans une équipe co-dirigée par le docteur Sophie VAULONT et le professeur Axel KAHN. Je me suis ainsi familiarisé avec la souris comme « outil » de recherche (gestion d'un élevage, établissement de nouvelles lignées, génotypage, phénotypage). Je travaillais initialement sur le métabolisme du glucose mais j'ai complètement réorienté ma thématique de recherche au bout d'un an pour finalement identifier et caractériser une hormone, l'hepcidine, contrôlant l'homéostasie du fer.
J'ai été nommé chargé de recherche de grade 2 dans l'unité 409 de l'INSERM en octobre 2002 pour y développer une souche de souris exprimant une spectrine non érythroïde résistante à des mécanismes de protéolyse ciblée. Il s'agit donc toujours d'appréhender certaines fonctions des spectrines mais dans un contexte in vivo. En janvier 2005 j'ai intégré l'unité 665 de l'INSERM dirigée par Yves COLIN afin de poursuivre ce projet. Aujourd'hui, je suis chargé de recherche de grade 1.
Le chapitre scientifique de ce mémoire est divisé en deux parties distinctes : la première traite de mon travail sur la spectrine tandis que la seconde porte sur l'hepcidine. Chaque partie est composée d'une introduction au sujet suivie d'un résumé des travaux que j'ai effectués et/ou dirigés.
https://tel.archives-ouvertes.fr/tel-00285035

Droits : info:eu-repo/semantics/OpenAccess
tel-00285035
https://tel.archives-ouvertes.fr/tel-00285035
https://tel.archives-ouvertes.fr/tel-00285035/document
https://tel.archives-ouvertes.fr/tel-00285035/file/HDR_Titre_et_travaux_-_Gael_Nicolas.pdf

Résumé : La tuberculose (TB), maladie infectieuse contagieuse, est causée par une mycobactérie appartenant au complexe Mycobacterium tuberculosis (MTBC). Malgré de nombreuses campagnes de vaccination par le BCG (Bacilles de Calmette et Guérin) et les traitements antituberculeux, on observe une réémergence de la maladie depuis les années 80. Ce bouleversement s’explique par la coïnfection avec le virus du VIH/SIDA, la désorganisation des systèmes de santé et par l’apparition des bactéries résistantes aux principaux antibiotiques antituberculeux. Dans ce contexte une meilleure connaissance des mouvements et de l’évolution des clones circulants du bacille tuberculeux permettrait de détecter plus rapidement et de façon plus pertinente l’émergence d’épidémies. Le contrôle et la surveillance de la maladie représentent des moyens essentiels pour lutter contre l’expansion mondiale de la tuberculose. C’est ainsi que l’unité de la Tuberculose et des Mycobactéries de l’Institut Pasteur de la Guadeloupe (IPG) a mis en place une base de données de profils génotypiques pour l’étude de l’épidémiologie globale de la tuberculose. Dans le cadre de cette thèse, nous décrirons les méthodes de bioinformatique qui ont été utilisées pour la gestion et l’exploitation de la 6ème version (SITVIT2) de cette base de données des génotypes pour mieux comprendre l’évolution et la dissémination mondiale du bacille tuberculeux. Cette base intègre aussi plusieurs marqueurs moléculaires tels que les MIRU-VNTRs (« mycobacterial interspersed repetitive units-variable number of tandem repeats ») et le Spoligotype43 servant à mieux décrire et identifier les familles de profils génotypiques du MTBC. La banque de données SITVIT2 ne cesse d’évoluer, et elle contient actuellement des informations épidémiologiques sur 111 635 isolats cliniques. Cette base de données est consultable en ligne à l’adresse suivante : http://www.pasteur-guadeloupe.fr:8081/SITVIT2/. Nous avons également réalisé une base de données nommée SITVITBovis qui est dédiée à la tuberculose bovine. Cette base de données sera accessible à l’adresse : http://www.pasteur-guadeloupe.fr:8081/SITVIT_Bovis/. Parallèlement au développement et à la gestion des bases de données, ce travail de thèse s’est appuyé sur plusieurs études épidémiologiques et phylogéographiques mettant en corrélation les données disponibles sur la résistance aux médicaments ou les caractéristiques démographiques (dont le sexe, l’âge, le statut VIH, et l’origine du patient). Notre initiative de recherche permet ainsi d’améliorer la caractérisation phylogénétique détaillée des lignées du MTBC, ainsi que l’épidémiologie des clones en circulation, afin d’élaborer une cartographie géographique des isolats cliniques prédominants pour les bacilles tuberculeux principalement impliqués dans la maladie, à l’échelle nationale, régionale et mondiale. La superposition ultérieure de ces cartes avec des données sociopolitiques, économiques et démographiques obtenues auprès de Systèmes d’information géographique (SIG) ont permis de dresser un portrait précis des disparités actuelles par pays ou sous-région. Cette thèse représente une importante collaboration avec plusieurs équipes de chercheurs travaillant également dans le domaine de l’épidémiologie moléculaire de la tuberculose. L’objectif à long terme de ce travail, est d’optimiser la structure de la base, et de pérenniser l’enrichissement de celle-ci (notamment par l’automatisation et la facilité de la saisie de données). Une représentation optimale et une meilleure accessibilité des données de la base conforteraient les efforts faits pour le contrôle et la surveillance de la TB dans monde.
Tuberculosis (TB) is a contagious infectious disease caused by mycobacteria belonging to the Mycobacterium tuberculosis complex (MTBC). Despite numerous campaigns of vaccination by the BCG (Bacillus Calmette-Guérin) vaccine, and TB treatments, there was a resurgence of the disease since the 80s. This disruption is due to coinfection with HIV/AIDS, disorganization of health systems and the emergence of bacteria resistant to anti-TB drugs. In this context, a better understanding of the movements and changes of circulating clones of tubercle bacilli would detect faster and more relevant emerging epidemics. The control and monitoring of the disease are essential means to fight against the worldwide spread of tuberculosis. Thus the TB and Mycobacteria unit of the Pasteur Institute of Guadeloupe (IPG) has developed a database of genotypic profiles for the study of global epidemiology of tuberculosis.In this thesis, we discuss the Bioinformatical methods that have been used for the management and development of the 6th version (SITVIT2) of this database of genotypes to better understand the evolution and global dissemination of the tubercle bacillus. The database also includes several molecular markers such as MIRU-VNTRs (mycobacterial interspersed repetitive units- variable number of tandem repeats) and Spoligotype43 allowing a better description and identification of the families of genotypic profiles of Mycobacterium tuberculosis complex. SITVIT2 database is constantly evolving, and it currently contains epidemiological information on 111,635 clinical isolates. This database is available online at the following address: http://www.pasteur-guadeloupe.fr:8081/SITVIT2/. We also developed a database named "SITVITBovis", which is dedicated to bovine tuberculosis. This database will be accessible at: http://www.pasteur-guadeloupe.fr:8081/SITVIT_Bovis/.Alongside the development and management of databases, this work was based on several epidemiological and phylogeographic studies correlating data on drug resistance or demographic characteristics (including sex, age, HIV status, and the origin of the patient). Our research initiative is thus focused to further improve in depth phylogenetic characterization of MTBC lineages, as well as the epidemiological analysis of circulating clones to generate evidence-based geographical mapping of predominant clinical isolates of tubercle bacilli causing the bulk of the disease both at country and regional level. Further superposition of these maps with socio-political, economical and demographical available through Geographic Information Systems (GIS) allows to have a precise view of prevailing disparities at the level of country or sub-region. This thesis represents an important collaboration with several researchers teams also working in the field of molecular epidemiology of tuberculosis.The long-term goal of this work is to further optimize the database structure, and sustain enriching it (including automation and ease of data entry). Optimum performance and accessibility of data in the database would reinforce efforts to control and surveillance of TB in the world.

http://www.theses.fr/2014AGUY0791/document

Éditeur(s) : HAL CCSD
Résumé :  
For a comprehensive evaluation of human influences on the genetic system, the simulation model EGO-GENE was developed. The model combines population genetic and population dynamic processes with forest growth models. The dynamics of genetic structures (single locus and multilocus genotypes up to 200 loci) can be simulated. Spatial and temporal genetic dynamics are included in the model. Overlapping or separated generations can be created and different modes of mating systems can be implemented. The model can be run with empirical and fictitious input data. The simulated genetic structures can be directly analysed with established genetic analysis programmes. An example demonstrates the use of the model far validation of interactions among components of the mating system. Another example demonstrates the applicability of the model in decision-making for seed sampling strategies. The genetic differences between the adult trees and the harvested seeds and the danger of genetic drift regarding to different seed sampling strategies are investigated by use of the genetic distance and the reproductively effective population size.
Silvae genetica

hal-01032083
https://hal.archives-ouvertes.fr/hal-01032083

Éditeur(s) : HAL CCSD National Academy of Sciences
Résumé : International audience
Natal philopatry, the return of individuals to their natal area for reproduction, has advantages and disadvantages for animal populations. Natal philopatry may generate local genetic adaptation, but it may also increase the probability of inbreeding that can compromise persistence. Although natal philopatry is well documented in anadromous fishes, marine fish may also return to their birth site to spawn. How philopatry shapes wild fish populations is, however, unclear because it requires constructing multigenerational pedigrees that are currently lacking for marine fishes. Here we present the first multigenerational pedigree for a marine fish population by repeatedly genotyping all individuals in a population of the orange clownfish (Amphiprion percula) at Kimbe Island (Papua New Guinea) during a 10-y period. Based on 2927 individuals, our pedigree analysis revealed that longitudinal philopatry was recurrent over five generations. Progeny tended to settle close to their parents, with related individuals often sharing the same colony. However, successful inbreeding was rare, and genetic diversity remained high, suggesting occasional inbreeding does not impair local population persistence. Local reproductive success was dependent on the habitat larvae settled into, rather than the habitat they came from. Our study suggests that longitudinal philopatry can influence both population replenishment and local adaptation of marine fishes. Resolving multigenerational pedigrees during a relatively short period, as we present here, provides a framework for assessing the ability of marine populations to persist and adapt to accelerating climate change.
ISSN: 0027-8424

hal-01417471
https://hal-univ-perp.archives-ouvertes.fr/hal-01417471
DOI : 10.1073/pnas.1611797113

Éditeur(s) : Wiley-blackwell
Résumé : The history of colonization and dispersal in fauna distributed among deep-sea chemosynthetic ecosystems remains enigmatic and poorly understood because of an inability to mark and track individuals. A combination of molecular, morphological and environmental data improves understanding of spatial and temporal scales at which panmixia, disruption of gene flow or even speciation may occur. Vestimentiferan tubeworms of the genus Escarpia are important components of deep -sea cold seep ecosystems, as they provide long-term habitat for many other taxa. Three species of Escarpia, Escarpia spicata [Gulf of California (GoC)], Escarpia laminata [Gulf of Mexico (GoM)] and Escarpia southwardae (West African Cold Seeps), have been described based on morphology, but are not discriminated through the use of mitochondrial markers (cytochrome oxidase subunit 1; large ribosomal subunit rDNA, 16S; cytochrome b). Here, we also sequenced the exon-primed intron-crossing Haemoglobin subunit B2 intron and genotyped 28 microsatellites to (i) determine the level of genetic differentiation, if any, among the three geographically separated entities and (ii) identify possible population structure at the regional scale within the GoM and West Africa. Results at the global scale support the occurrence of three genetically distinct groups. At the regional scale among eight sampling sites of E. laminata (n=129) and among three sampling sites of E. southwardae (n=80), no population structure was detected. These findings suggest that despite the patchiness and isolation of seep habitats, connectivity is high on regional scales.
Molecular Ecology (0962-1083) (Wiley-blackwell), 2013-08 , Vol. 22 , N. 16 , P. 4147-4162

Droits : 2013 John Wiley & Sons Ltd
http://archimer.ifremer.fr/doc/00152/26354/24515.pdf
DOI:10.1111/mec.12379
http://archimer.ifremer.fr/doc/00152/26354/

Éditeur(s) : HAL CCSD Wiley
Résumé : The extent of gene dispersal is a fundamental factor of the population and evolutionary dynamics of tropical tree species, but directly monitoring seed and pollen movement is a difficult task. However, indirect estimates of historical gene dispersal can be obtained from the fine-scale spatial genetic structure of populations at drift-dispersal equilibrium. Using an approach that is based on the slope of the regression of pairwise kinship coefficients on spatial distance and estimates of the effective population density, we compare indirect gene dispersal estimates of sympatric populations of 10 tropical tree species. We re-analysed 26 data sets consisting of mapped allozyme, SSR (simple sequence repeat), RAPD (random amplified polymorphic DNA) or AFLP (amplified fragment length polymorphism) genotypes from two rainforest sites in French Guiana. Gene dispersal estimates were obtained for at least one marker in each species, although the estimation procedure failed under insufficient marker polymorphism, limited sample size, or inappropriate sampling area. Estimates generally suffered low precision and were affected by assumptions regarding the effective population density. Averaging estimates over data sets, the extent of gene dispersal ranged from 150 m to 1200 m according to species. Smaller gene dispersal estimates were obtained in species with heavy diaspores, which are presumably not well dispersed, and in populations with high local adult density. We suggest that limited seed dispersal could indirectly limit effective pollen dispersal by creating higher local tree densities, thereby increasing the positive correlation between pollen and seed dispersal distances. We discuss the potential and limitations of our indirect estimation procedure and suggest guidelines for future studies
ISSN: 0962-1083

hal-01031603
https://hal.archives-ouvertes.fr/hal-01031603
DOI : 10.1111/j.1365-294X.2005.02785.x

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
Sickle cell anemia (SCA) and hemoglobin SC (HbSC) disease are the two most common forms of sickle cell disease (SCD), a frequent hemoglobinopathy which exhibits a highly variable clinical course. Although high levels of microparticles (MPs) have been consistently reported in SCA and evidence of their harmful impact on the SCA complication occurrences have been provided, no data on MP pattern in HbSC patients has been reported so far. In this study, we determined and compared the MP patterns of 84 HbSC and 96 SCA children, all at steady-state, using flow cytometry. Most of circulating MPs were derived from platelets (PLTs) and red blood cells (RBCs) in the two SCD syndromes. Moreover, we showed that HbSC patients exhibited lower blood concentration of total MPs compared to SCA patients, resulting mainly from a decrease of MP levels originated from RBCs and to a lesser extent from PLTs. We did not detect any association between blood MP concentrations and the occurrence of painful vaso-occlusive crises, acute chest syndrome and pulmonary hyper-tension in both patient groups. We also demonstrated for the first time, that whatever the considered genotype, RBC-derived MPs exhibited higher externalized phosphatidylserine level and were larger than PLT-derived MPs.
ISSN: 1932-6203

hal-01668322
https://hal.univ-antilles.fr/hal-01668322
https://hal.univ-antilles.fr/hal-01668322/document
https://hal.univ-antilles.fr/hal-01668322/file/journal.pone.0177397.pdf
DOI : 10.1371/journal.pone.0177397

Éditeur(s) : Springer
Résumé : Clonality and genetic structure of the coral Pocillopora damicornis sensu lato were assessed using five microsatellites in 12 populations from four islands of the Society Archipelago (French Polynesia) sampled in June 2008. The 427 analysed specimens fell into 132 multilocus genotypes (MLGs), suggesting that asexual reproduction plays an important role in the maintenance of these populations. A haploweb analysis of ITS2 sequences of each MLG was consistent with all of them being conspecific. Genetic differentiation was detected both between and within islands, but when a single sample per MLG was included in the analyses, the populations turned out to be nearly panmictic. These observations provide further evidence of the marked variability in reproductive strategies and genetic structure of P. damicornis throughout its geographic range; comparison with results previously obtained for the congeneric species Pocillopora meandrina underlines the importance of life history traits in shaping the genetic structure of coral populations
Marine Biology (0025-3162) (Springer), 2014-03 , Vol. 161 , N. 3 , P. 531-541

Droits : Springer-Verlag Berlin Heidelberg 2013
http://archimer.ifremer.fr/doc/00171/28209/26518.pdf
DOI:10.1007/s00227-013-2355-9
http://archimer.ifremer.fr/doc/00171/28209/