Éditeur(s) : HAL CCSD
Résumé : During the course of their life cycle organisms are exposed to natural environment variations capable of inducing physiological, morphological and behaviour changes, thus a phenotypic plasticity. Phenotypic plasticity is the ability of a genotype to generate a new phenotype following exogeneous or endogeneous stress. Here, we investigated the phenotypic plasticity of the non-calcifying symbiotic cnidarian Anemonia viridis at multiple levels of structural complexity, in vivo and in vitro. In vivo, we determined the mechanisms behind the phenotypic plasticity under expected future climate change (i.e. ocean acidification and ocean warming). Our results show physiological changes in the inorganic carbon use of the sea anemone A. viridis exposed to high pCO2 during a long-term stress in natura or a short-term stress in controlled conditions. We then observed an equivalent decrease in carbonic anhydrase activity, a key enzyme of cnidarian carbon concentrating mechanisms. Also, we demonstrated that an increase in seawater temperature modified the response observed during a high pCO2 scenario. In vitro, we established a viable primary cell culture from regenerating tentacles of A. viridis. We determined the gastrodermal tissue origin of the cultivated cells and validated the use of this new tool to the in vitro study of stress response at the cellular level. The set-up of this powerful in vitro tool will open a multitude of perspectives for the study of cellular responses to exogeneous stress (as global change perturbations) and to endogeneous stress (as the symbiosis constraints experienced by symbiotic cnidarians)
Durant leur cycle de vie, les organismes sont exposés à des variations environnementales capables d'induire des changements physiologiques, morphologiques et comportementaux, résultant d’une plasticité phénotypique. La plasticité phénotypique est la capacité d'un génotype à générer un nouveau phénotype suite à un stress. Ici, nous avons étudié la plasticité phénotypique d’un Cnidaire symbiotique et non-calcifiant, l’anémone de mer Anemonia viridis, à de multiples niveaux de complexité structurale, in vivo et in vitro. In vivo, nous avons identifié les mécanismes sous-jacents de la plasticité phénotypique potentiellement induits par les futurs changements climatiques (acidification et réchauffement des océans). Nos résultats montrent des modifications dans l'utilisation du carbone inorganique par A. viridis exposée à une forte pCO2 lors d’un stress chronique in natura ou lors d’un stress court en conditions contrôlées. Nous avons ainsi observé une diminution des activités anhydrase carbonique, une enzyme clé des mécanismes de concentration du carbone chez les Cnidaires. Nous avons aussi démontré que l'augmentation concomittante de la température modifie la réponse observée lors d'une élévation seule de la pCO2. In vitro, nous avons établi une culture de cellules primaires viables issue de tentacules d’A. viridis en régénération. Nous avons déterminé l'origine gastrodermale des cellules cultivées et validé l'utilisation de ce nouvel outil pour l'étude de la réponse au stress au niveau cellulaire. Ce nouvel outil ouvre une multitude de perspectives pour l'étude des réponses cellulaires aux stress exogènes (changement climatique) et endogènes (contraintes dues à la symbiose)
https://tel.archives-ouvertes.fr/tel-01674220

Droits : info:eu-repo/semantics/OpenAccess
NNT : 2016AZUR4136
tel-01674220
https://tel.archives-ouvertes.fr/tel-01674220
https://tel.archives-ouvertes.fr/tel-01674220/document
https://tel.archives-ouvertes.fr/tel-01674220/file/2016AZUR4136.pdf

Éditeur(s) : INRA : Institut National de la Recherche Agronomique Université des Antilles. Service commun de la documentation
Extrait de : 52e congrès annuel de la Société caribéenne des plantes alimentaires / 52nd annual meeting of the Caribbean food crops society (CFCS), du 10 au 16 juillet 2016. INRA, CFCS
Description : The Creole pig has always been part of the rural and suburban landscape of Martinique. Currently, this breed is not integrated into a research and conservation program. The Natural Park of Martinique Region (PNRM) has the objective to maintain and valorize the genetic heritage of Martinique?s Creole pig and develop a niche business. Based on PNRM knowledge, some Creole pigs live freely in the mountains in the North, in the South coast and in a few disparate traditional breeders located in the countryside. It is essential to carry out an inventory of the local pig population to propose a scheme for conservation and economic development. In order to favour the appropriation of the Creole pig niche, the PNRM, as a decision maker, acts in a systemic and holistic way by considering the whole Martinican territory and the pig sub-sector: producers involved in the COOPMAR pig farmers? cooperative, researchers of INRA (FWI), the food chain and at least (in a second phase) the consumers and the Martinican society. First of all, the pig farmers are involved (private family farms and specialised pig producers). Researchers and technicians from PNRM and INRA- URZ (Animal production research unit) and INRA-PTEA (Tropical platform in animal experimentation) are performing experimental studies both in controlled conditions and in farms, in order to: i) determine phenotypic and genetic characteristics of Martinique?s Creole pigs in comparison with other pig breeds from the Caribbean area; ii) help at designing genetic management to maintain the population and avoiding inbreeding; iii) help at defining feeding management by a) establishing, at the whole territorial food chain, an inventory of co or by-products available for pig feeding; b) implementing experimental studies in technology for conservation; c) implementing feeding and growing experiments and finally iv) help at defining eco-friendly production systems a) aiming at generate an adequate revenue and b) focusing on ecosystem services such as meat quality, socio-cultural services and circular economy. Le porc créole a toujours fait partie du paysage rural et suburbain de la Martinique. Actuellement, cette race n'est pas intégrée dans un programme de recherches et de conservation. Le parc naturel de la région de la Martinique (PNRM) a l'objectif pour maintenir et valoriser l'héritage génétique du porc créole de la Martinique et pour développer des créneaux. Basé sur la connaissance de PNRM, quelques porcs créoles vivent librement dans les montagnes dans le nord, dans la côte sud et chez quelques éleveurs traditionnels disparates situés dans la campagne. Il est essentiel d'effectuer un inventaire de la population locale de porc pour proposer un plan pour la conservation et le développement économique. Afin de favoriser l'appropriation du créneau créole de porc, le PNRM, comme décideur, agit d'une manière systémique et holistique en considérant tout le territoire de la Martinique et sous-secteur de porc : producteurs impliqués dans la coopérative d'agriculteurs de porc de COOPMAR, les chercheurs d'AICN (FWI), la chaîne alimentaire et au moins (dans une deuxième phase) les consommateurs et la société Martiniquaise. Tout d'abord, les agriculteurs de porc sont impliqués (les fermes privées de famille et les producteurs de porc spécialisés). Les chercheurs et les techniciens de PNRM et AICN URZ (unité de recherches de production animale) et INRA-PTEA (plate-forme tropicale chez l'expérimentation animale) réalisent des études expérimentales dans des conditions commandées et dans les fermes : i) déterminent des caractéristiques phénotypiques et génétiques des porcs créoles de la Martinique en comparaison d'autres races de porc à partir du secteur des Caraïbes ; ii) aide à concevoir la gestion génétique pour maintenir la population et à éviter l'endogamie ; iii) aide à définir la gestion de alimentation a) en établissant, à la chaîne alimentaire territoriale de totalité, à un inventaire de Co ou aux sous-produits disponibles pour l'alimentation de porc ; b) mise en oeuvre des études expérimentales en technologie pour la conservation ; c) mettant en application des expériences de alimentation et croissantes et finalement iv) aide à définir viser qui respecte l'environnement des systèmes de production a) produisent de à revenu approprié et b) se concentrant sur des services d'écosystème tels que la qualité de viande, des services socioculturels et l'économie circulaire.
Siècle(s) traité(s) : 21
Droits : CC-BY-NC-ND - Attribution - Pas d'utilisation commerciale - Pas de modification
Permalien : http://www.manioc.org/fichiers/V16263
V16263

Éditeur(s) : HAL CCSD
Résumé : International audience
The prevalence of bone deformities, particularly linked with mineral deficiency, is an important issue for fish production. Juvenile triploid rainbow trout (Oncorhynchus mykiss) were fed a low-phosphorus (P) diet for 27 weeks (60 to 630 g body mass). At study termination, 24.9% of the fish fed the low-P diet displayed homogeneous biconcave vertebrae (deformed vertebrae phenotype), while 5.5% displayed normal vertebral phenotypes for the entire experiment. The aim of our study was to characterize the deformed phenotype and identify the putative genes involved in the appearance of P deficiency-induced deformities. Both P status and biomechanical measurements showed that deformed vertebrae were significantly less mineralized (55.0 ± 0.4 and 59.4 ± 0.5,% ash DM, for deformed and normal vertebrae, respectively) resulting in a lower stiffness (80.3 ± 9.0 and 140.2 ± 6.3 N/mm, for deformed and normal phenotypes, respectively). The bone profiles based on μCT observations showed no difference in the osteoclastic resorption while no difference in matrix production was observed between deformed (total bone area 5442.0 ± 110.1 μm2) and normal vertebrae (total bone area 5931.2 ± 249.8 μm2) in this study. Consequently, the lower P content rather results from a reduced degree of mineralization in the deformed phenotype. Finally, we quantified differential gene expression between deformed vertebrae (pronounced biconcave) and normal phenotype by employing deep RNA-sequencing and mapping against a reference bone transcriptome for rainbow trout. In total, 1289 genes were differentially expressed. Among them, in deformed fish we observed that BGLAP, MGP and NOG, an inhibitor of BMP signalling pathway, were up-regulated while COL11a1 was down-regulated. These genes are central actors involved in the reduced degree of mineralization triggering vertebral deformities. These results will further the understanding of P deficiency-induced deformities; hence providing new tools for improved P management in production settings
Journal of Next Generation Sequencing & Applications

hal-01545768
https://hal.archives-ouvertes.fr/hal-01545768
DOI : 10.4172/2469-9853.1000112

Éditeur(s) : HAL CCSD
Résumé : Understanding of the mechanisms driving diversification of species is a significant way to improve the management of ecosystems, predict the impacts of climate change and understand the actual and past biodiversity level. The aim of this thesis is to understand and comprehend genetic mechanisms behind the diversification of species in the presence of gene flow. This thesis is focused on the biological model Symphonia globulifera, which presents two ecotypes: the S.globulifera, specialist of seasonally flooded lowlands and S.sp1, specialist of terra firme. These two ecotypes show low genetic differentiation, despite the presence of two apparent phenotypes. A first part of this thesis was to test the presence of local adaptation of this using reciprocal transplant experiment gardens, allowing the understanding of the ecotypes distributions in their natural habitats. Then, this local adaptation in the presence of gene flow, directed me to the regulation of gene methylation in order to see the role this brand of epigenetics can have in the divergence of the ecotypes. In a third part of the thesis, new generation sequencing of the transcriptome ecotypes in reciprocal gardens transplantations allowed me to show the evidence of gene regulation to differentiate the ecotypes. This work thesis is based on phenotype records data, AFLP genotyping and high-throughput sequencing of the transcriptome, in order to show the important value of gene regulation in the divergence of the locally adapted ecotypes, and a weak role of DNA methylation in the establishment of local adaptation.
Connaitre et appréhender les mécanismes de la diversification des espèces est important pour la gestion des écosystèmes, la prévision des impacts des changements climatiques et la compréhension de la biodiversité actuelle et passée. Le but de cette thèse est de comprendre et de déceler les mécanismes génétiques à l’origine de la diversification des espèces en présence de flux de gènes. Cette thèse se focalise sur le modèle biologique Symphonia globulifera, qui compte deux écotypes : le S.globulifera spécialiste de la terra firme et le S.sp1, spécialiste des bas-fonds. Ces deux écotypes montrent une faible différenciation génétique, malgré la présence de deux phénotypes différents.Une première étape a été de mettre en évidence la présence d’une adaptation locale au sein de cette espèce, par le biais d’une expérimentation de jardins de transplantation réciproques, permettant d’expliquer la répartition des écotypes dans leur habitat naturel. Ensuite, dans le but d’identifier les mécanismes sous-jacent à cette adaptation locale, j’ai testé l’hypothèse que la méthylation des gènes pourrait être une marque de l’épigénétique contribuant à la divergence des écotypes, par l’utilisation d’enzyme sensibles à la méthylation dans un protocole de génotypage AFLP. Enfin, un séquençage haut-débit du transcriptome des écotypes en jardins de transplantation réciproques m’a permis de mettre en évidence une expression différentielle des gènes entre les écotypes, qui pourrait expliquer les différences phénotypiques observées entre les écotypes malgré une faible différentiation génétique. Ces travaux de thèse s’appuie, ainsi, sur des données de traits phénotypiques, de génotypage AFLP et de séquençage à haut débit du transcriptome pour montrer la valeur importante de la régulation des gènes dans la divergence des écotypes adaptés localement, et un faible rôle de la méthylation de l’ADN dans l’établissement cette adaptation locale.
https://tel.archives-ouvertes.fr/tel-01405400

NNT : 2015YANE0005
tel-01405400
https://tel.archives-ouvertes.fr/tel-01405400
https://tel.archives-ouvertes.fr/tel-01405400/document
https://tel.archives-ouvertes.fr/tel-01405400/file/these_-_tinaut.pdf

Éditeur(s) : HAL CCSD Instituto Oswaldo Cruz, Ministério da Saúde
Résumé : International audience
Leishmania are protozoan parasites that show remarkable diversity, as revealed by the various clinical forms of leishmaniasis,which can range from mild skin lesions to severe metastatic cutaneous/mucosal lesions. The exact nature andextent of Leishmania phenotypic diversity in establishing infection is not fully understood. In order to try to understandsome aspects of this diversity, we subcutaneously infected BALB/c mice with first and second generation subclones of aL. amazonensis strain isolated from a patient (BA125) and examined in vivo lesion growth rate and antimony susceptibility.In vivo fast-, medium- and slow-growing subclones were obtained; moreover, fast-growing subclones could generateslow-growing subclones and inversely, revealing the continuous generation of diversity after passage into mice. Noantimony-resistant subclone appeared, probably a rare occurrence. By tagging subclone cells with a L. amazonensisgenomic cosmid library, we found that only a very small number of founding cells could produce lesions. Leishmaniaclones transfected with in vivo selected individual cosmids were also diverse in terms of lesion growth rate, revealing thecosmid-independent intrinsic characteristics of each clone. Our results suggest that only a few of the infecting parasitesare able to grow and produce lesions; later, within the cell mixture of each lesion, there coexist several parasite populationswith different potentialities to grow lesions during the next infection round. This may reflect a sort of programmedheterogeneity of individual parasites, favoring the survival of some individuals in various environmental conditions.
ISSN: 0074-0276

hal-01557855
https://hal-univ-perp.archives-ouvertes.fr/hal-01557855
DOI : 10.1590/0074-02760160280

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
The pearl oyster Pinctada margaritifera has the specific ability to produce pearls with the widest range of coloursamong all pearl oyster species. This pearl colour diversity originates from the mantle biomineralising tissue(graft) of the donor oyster, which is originally responsible for the variety of colours of the inner shell surface.This study aimed to: 1) assess the geographic distribution and establish a first stocklist of the colourful oysterphenotypes used as donors in French Polynesia, and 2) investigate the phenotypic relation between inner shellcolouration and the corresponding colour of harvested pearls. With the support of a pearl farmers' network,we investigated the different donor phenotype frequencies among five collection sites (Ahe, Apataki, Takaroa,TakumeandMangareva). This donor evaluation was made during grafting of pearl oysters (N=49,938) obtainedfrom collector stations. Results showed that pearl production is mainly based on six common colourful donorphenotypes classified as monochromatic and polychromatic profiles, which shown different frequenciesamong the collection sites. Experimental grafts (N=4640)were then realised and subsequent culture conductedat a single site in order to avoid pearl colour variation due to environmental influences. Traceability between donors(N=232) and pearls (N=2776), revealed that: 1) yellow (gold) and aubergine (reddish) pearls could bemostly obtained by using the monochromatic yellowand red donor phenotypes, respectively, and 2) one third toone quarter of grey pearlswas inevitably harvested, whatever the polychromatic phenotype chosen as the donor,which leaves at least half the harvest composed of the attractive green and peacock colours. This preliminarystocklist of colour range together with analysis of the colour phenotype transmission between inner shell andpearl provide the basis for producing multiple pearl oyster “colour lines” through hatchery propagation andwould be helpful for future selective breeding programs.Statement of relevance: Donor shell colour selection predict colours of pearls
ISSN: 0044-8486

hal-01489153
https://hal-univ-perp.archives-ouvertes.fr/hal-01489153
DOI : 10.1016/j.aquaculture.2016.10.017

Éditeur(s) : HAL CCSD Instituto Oswaldo Cruz, Ministério da Saúde
Résumé : International audience
Leishmania are protozoan parasites that show remarkable diversity, as revealed by the various clinical forms of leishmaniasis, which can range from mild skin lesions to severe metastatic cutaneous/mucosal lesions. The exact nature and extent of Leishmania phenotypic diversity in establishing infection is not fully understood. In order to try to understand some aspects of this diversity, we subcutaneously infected BALB/c mice with first and second generation subclones of a L. amazonensis strain isolated from a patient (BA125) and examined in vivo lesion growth rate and antimony susceptibility. In vivo fast-, medium- and slow-growing subclones were obtained; moreover, fast-growing subclones could generate slow-growing subclones and inversely, revealing the continuous generation of diversity after passage into mice. No antimony-resistant subclone appeared, probably a rare occurrence. By tagging subclone cells with a L. amazonensis genomic cosmid library, we found that only a very small number of founding cells could produce lesions. Leishmania clones transfected with in vivo selected individual cosmids were also diverse in terms of lesion growth rate, revealing the cosmid-independent intrinsic characteristics of each clone. Our results suggest that only a few of the infecting parasites are able to grow and produce lesions; later, within the cell mixture of each lesion, there coexist several parasite populations with different potentialities to grow lesions during the next infection round. This may reflect a sort of programmed heterogeneity of individual parasites, favoring the survival of some individuals in various environmental conditions.
ISSN: 0074-0276

hal-01489008
https://hal-univ-perp.archives-ouvertes.fr/hal-01489008

Éditeur(s) : Actes du 6e colloque national BRG, La Rochelle, 2-3-4 octobre 2006
Résumé : Previous studies have shown heritable variation in larval developmental traits in the Pacific oyster Crassostrea gigas. In order to study the genetic consequences of production of oyster larvae in hatcheries, two factors, specific to hatcheries, were examined: the effect of discarding the smallest larvae (i.e. culling) and the effect of temperature (20°C versus 26°C). A mixed-family approach was used in order to infer the genetic composition of larval populations and family assignment, limiting possible environmental bias and allowing the study of a relatively large number of families using a limited number of larval tanks. Our results show that three multiplexed highly polymorphic microsatellite markers are a powerful tool for family assignment and, consequently, for the study of bivalve larvae genetics. Culling, by selective sieving of the smallest larvae is an advantageous practice at a phenotypic scale as it reduced variance in larval size, variance of developmental rate and time to settlement. Culling of 50% of the larval population only led to 15% less spat, showing a positive phenotypic correlation between larval growth and settlement success. However, culling represents a substantial risk for diversity loss, because it increases the variance of reproductive success among parental oysters. The effective population sizes of early settling cohorts of settlement were lower than those of later ones. Our results show that the settlement of slow growing larvae significantly contributes to minimizing the variability of reproductive success and therefore to maximizing genetic diversity. These results corroborate the low estimations of variability of broodstocks sampled in several French commercial hatcheries, relative to natural populations. The genetic composition of the larval population and the resulting spat was significantly different between the two tested temperatures, revealing genotype x environment interaction for survival. Similarly, genotype x environment interaction was also observed for larval growth as a higher temperature exerted a positive influence on the expression of genetic variability for this trait. Consequently, we can conclude that a temperature of 26°C coupled with culling, to common practice in oyster hatcheries, is likely to amplify the selection pressure for fast growing larvae. To test for this hypothesis, we compared larval developmental traits in the progeny of a hatchery broodstock closed for 7 generations, with the progeny of wild oysters and the two possible hybrids. Our results show that selection of fast growing larvae can counteract presumed inbreeding depression, due to higher mean relatedness among hatchery broodstock than in the wild. Genetic effects of intensive rearing conditions at larval stage are significant and should be taken into account in hatchery practices, especially in terms of genetic diversity management.
Afin d'étudier les conséquences génétiques des pratiques de production en écloserie d'huître creuse, deux facteurs ont été examinés : l'élimination des petites larves et la température. Nos résultats montrent que l'assignation de parenté par marqueurs microsatellites est un outil performant pour les études génétiques en phase larvaire de familles élevées en mélange. Bien qu'avantageux d'un point de vue phénotypique, le tamisage sélectif représente un risque de perte de diversité. La fixation des larves à croissance lente permet en effet de minimiser la variabilité du succès reproducteur et de fait, de maximiser la variabilité génétique. Ces résultats corroborent les estimations de variabilité sur les stocks d'écloseries françaises où l'on constate une diversité allélique inférieure à celle de populations issues du milieu naturel. La température exerce également une influence sur la précocité de l'expression de la variabilité génétique pour la croissance larvaire. Ainsi une température élevée associée à une procédure de tamisage peut amplifier l'effet sélectif. Enfin, la sélection de larves à croissance rapide semble démontrée, s'opposant à la dépression de consanguinité présumée. Les conditions d'élevage peuvent donc avoir un effet génétique significatif qui devrait être pris en considération dans les pratiques d'écloserie, notamment dans la gestion de la diversité génétique.

Droits : info:eu-repo/semantics/openAccess
http://archimer.ifremer.fr/doc/2006/acte-1505.pdf
http://archimer.ifremer.fr/doc/00000/1505/

Résumé : Les pathologies inflammatoires démyélinisantes primitives du système nerveux central (SNC) sont dominées par deux entités : la sclérose en plaques (SEP) et la neuromyélite optique (NMO). Ces deux pathologies se différencient par : 1. leur phénotype, la NMO se caractérisant par une myélite extensive dans le plan transversal et longitudinal et peu de lésions encéphaliques initiales ; 2. leur sévérité, le pronostic de la NMO étant moins bon que celui de la SEP ; 3. leur mécanisme immunologique, puisque l’immunité humorale domine nettement dans la NMO, cette pathologie répondant peu ou pas aux traitementshabituellement prescrits dans la SEP. Un anticorps sérique (IgG-NMO) a été retrouvé chez les patients atteints de NMO avec une sensibilité de 50-70% et une spécificité de 90-100%. Cet anticorps a pour cible le principal canal hydrique du SNC, l’aquaporine-4 (AQP4), qui se situe principalement sur les pieds astrocytaires jalonnant la barrière hémato-encéphalique. La SEP est relativement familière des neurologues car décrite sur le plan épidémiologique et dans son histoire naturelle depuis plus d’un siècle à travers de larges séries réalisées parfois en population générale. Son approche thérapeutique progresse suite à des essais contrôlés qui s’accumulent depuis maintenant près de 20 ans. Toutefois, la majorité des travaux ont été effectués chez les populations Caucasiennes en raison de sa plus grande fréquence dans ces populations. A l’inverse, la NMO garde encore un relatif mystère à cause de sa relative rareté, l’établissement très récent de critères diagnostiques et une physiopathologie très récemment éclaircie par la découverte de l’IgG-NMO qui a indiscutablement suscité un regain d’intérêt de cette affection. Ainsi, son incidence est quasiment inconnue de même que sa susceptibilité génétique. La progression du handicap de la NMO qu’il soit visuel ou moteur à l’évidence sévère, ne repose toujours pas sur des chiffres précis, la description des lésions neuroradiologiques reste encore très embryonnaire. Enfin, même s’il existe un consensus pour traiter énergiquement les poussées de NMO et les espacer, il n’existe quasiment aucune étude prospective.
Introduction: Aim of the study is to describe épidemiology, phenotype and treatment of demyelinating inflammatory diseases of the central nervous system (CNS) namely multiple sclerosis (MS) and neuromyelitis optica (NMO) in French West Indies.Epidemiology: MS emerged in the French West Indian (FWI) population with an incidence of 1.27/100 000 (CI 95%: 1.16-1.38) for the period 1992-2007 while incidence of NMO remained stable at 0.19/100,000 (CI 95%: 0.15–0.23). Both migration in Metropolitean France (MF) and decrease of sun exposure were risk factors for MS acquisition in FWI. Phenotype and treatment of NMO: NMO is a very rapidly disabling disease with median times to reach DSS 3, 6 and 8 of one year, 8 years and 22 years respectively. However, treatment by plasma exchanges were shown to reduce sequellae of NMO attacks ; mitoxantrone and rituximab reduced significantly annualized relapse rate (ARR) from 1.7 to 0.29 (p<10-4) and from 1,34 to 0,56 (p=0.0005) respectively, improving dramatically natural course of NMO.Phenotype and treatment of MS: Absence of Migration in MF in MS patients was found to be the strongest independent predictive factor of disability progression to DSS 6 (hazard ratio, 2.59; p=0.0002); beside short time to DSS3 (p=0.005), later age at onset (p=0.005), and multi-symptomatic onset (p=0.03). Treatment of MS by interferon beta-1 had a moderate impact in MS while natalizimab proved to be highly effective by reducing drastically ARR and inflammatory parameters on magnetic resonance imaging. Conclusion: Spectrum of demyelinating inflammatory disorders of CNS has reversed in French West Indies with overrepresentation of MS. Agressive therapy is needed to improve prognosis of NMO. Rapidly increasing of its incidence makes MS a new public health problem in French West Indies.

http://www.theses.fr/2012AGUY0511/document

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
BACKGROUND: Mammalian spermatogenesis is a process that involves a complex expression program in both somatic and germ cells present in the male gonad. A number of studies have attempted to define the transcriptome of male meiosis and gametogenesis in rodents and primates. Few human transcripts, however, have been associated with testicular somatic cells and germ cells at different post-natal developmental stages and little is known about their level of germline-specificity compared with non-testicular tissues. METHODS: We quantified human transcripts using GeneChips and a total of 47 biopsies from prepubertal children diagnosed with undescended testis, infertile adult patients whose spermatogenesis is arrested at consecutive stages and fertile control individuals. These results were integrated with data from enriched normal germ cells, non-testicular expression data, phenotype information, predicted regulatory DNA-binding motifs and interactome data. RESULTS: Among 3580 genes for which we found differential transcript concentrations in somatic and germ cells present in human testis, 933 were undetectable in 45 embryonic and adult non-testicular tissues, including many that were corroborated at protein level by published gene annotation data and histological high-throughput protein immunodetection assays. Using motif enrichment analyses, we identified regulatory promoter elements likely involved in germline development. Finally, we constructed a regulatory disease network for human fertility by integrating expression signals, interactome information, phenotypes and functional annotation data. CONCLUSIONS: Our results provide broad insight into the post-natal human testicular transcriptome at the level of cell populations and in a global somatic tissular context. Furthermore, they yield clues for genetic causes of male infertility and will facilitate the identification of novel cancer/testis genes as targets for cancer immunotherapies.
ISSN: 0268-1161

hal-00877243
https://hal.archives-ouvertes.fr/hal-00877243
DOI : 10.1093/humrep/des301
PUBMED : 22926843

Éditeur(s) : HAL CCSD
Résumé : Macrophages (MΦ), well-known to play a key role in immune response, also respond to environmental toxic chemicals such as diesel exhaust particles (DEP), an air pollutant recently classified as carcinogenic to humans. MΦ are heterogeneous and plastic cells which activate according to their microenvironment into either an M1 subtype (so called classically activated or pro-inflammatory) under IFNγ and LPS stimulation or an M2 subtype (so called alternatively activated or anti-inflammatory) under IL-4 and/or IL-13 stimulation. However, potential effects of DEPs on M1/M2 MΦ polarization remain poorly documented. First, we characterized the expression marker of in vitro M-CSF-differentiated MΦ from human monocytes and activated into the M1 or M2 subtypes. Our main results show that M-CSF-generated MΦ considered as anti-inflammatory are actually able to switch to an M1 phenotype after IFNγ/LPS stimulation. Furthermore, the markers identified in this study were used to assess the impact of organic extracts of DEP (DEPe) on MΦ polarization and more generally on their physiology. DEPe alter some M1 and M2 markers expressed by polarized MΦ, without causing the overall inhibition of the M1 and M2 polarization process or the switch to a different phenotype. This phenotype alteration is associated with a decrease in the LPS-dependent inflammatory response in M1 MΦ and the chemotactic capacities in M2 MΦ. DEPe decrease the secretion of some cytokines and chemokines such as IL-6, IL-12p40 and CCL18 via AhR and/or Nrf2 activation. At the same time, we show that M1 and M2 MΦ in response to DEPe are able to secrete a sufficient level of a pro-fibrotic growth factor, the platelet derived growth factor B (PDGF-B) via AhR activation, leading to stimulation of lung fibroblast proliferation. Finally, these works show that DEPe have immunotoxic properties with regards to the physiology of human in vitro polarized MΦ. This immunotoxicity may then contribute to the deleterious effects of these urban environmental contaminants on human health.
Les macrophages (MΦ), des cellules clefs de la réponse immunitaire peuvent répondre à des contaminants environnementaux comme les particules diesel (DEP), des polluants atmosphériques récemment classés cancérigènes pour l'Homme. Les MΦ sont des cellules hétérogènes et plastiques qui s'activent en fonction de leur microenvironnement soit en MΦ M1 (dits classiquement activés ou pro-inflammatoires) sous l'effet de l'INFγ et du LPS soit en MΦ M2 (dits alternativement activés ou réparateurs) sous l'effet de l'IL-4 et/ou de l'IL-13. Les effets des DEP sur la polarisation M1/M2 des MΦ restent peu documentés. Nous avons dans un premier temps caractérisé l'expression des marqueurs des MΦ différenciés in vitro en présence de M-CSF à partir de monocytes humains et polarisés en sous-type M1 ou M2. Nos principaux résultats montrent que les MΦ différenciés au M-CSF considérés comme des MΦ anti-inflammatoires, sont en réalité capables de s'activer vers un phénotype M1 après une stimulation au LPS/IFNγ. De plus, les marqueurs mis en évidence au cours de ce travail ont permis d'évaluer l'impact d'extraits organiques de DEP (DEPe) sur la polarisation des MΦ et plus généralement sur leur physiologie. Les DEPe altèrent l'expression de certains marqueurs M1 et M2 des MΦ, sans toutefois provoquer d'inhibition globale des processus de polarisation M1 et M2 ou de transition d'un phénotype vers un autre. Cette altération du phénotype est associée à une diminution de la réponse inflammatoire LPS-dépendante dans les MΦ M1 et des capacités chimiotactiques des MΦ M2. Les DEPe diminuent la sécrétion de certaines cytokines et chimiokines comme l'IL-6, l'IL-12p40 et le CCL18 via l'activation d'AhR et/ou de Nrf2. Parallèlement, nous montrons que les MΦ M1 et M2 exposés aux DEPe sécrètent le platelet deried growth factor B (PDGF-B), un facteur de croissance profibrosant, via l'activation d'AhR en quantité suffisante pour stimuler la prolifération de fibroblastes pulmonaires. Au total, ces travaux démontrent que les DEP possèdent des propriétés immunotoxiques vis-à-vis de la physiologie des macrophages humains polarisés in vitro. Cette immunotoxicité pourrait participer aux effets délétères de ces contaminants environnementaux urbains sur la santé humaine.
https://tel.archives-ouvertes.fr/tel-01188679

NNT : 2015REN1S011
tel-01188679
https://tel.archives-ouvertes.fr/tel-01188679
https://tel.archives-ouvertes.fr/tel-01188679/document
https://tel.archives-ouvertes.fr/tel-01188679/file/JAGUIN_Marie.pdf

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
Background We conducted this systematic review and meta-analysis to address the open question of a possible association between the socioeconomic level of the neighborhoods in which pregnant women live and the risk of Congenital Heart Defects (CHDs), Neural Tube Defects (NTDs) and OroFacial Clefts (OFCs). Methods We searched MEDLINE from its inception to December 20th, 2015 for case-control, cohort and ecological studies assessing the association between neighborhood socioeconomic level and the risk of CHDs, NTDs and the specific phenotypes Cleft Lip with or without Cleft Palate (CLP) and Cleft Palate (CP). Study-specific risk estimates were pooled according to random-effect and fixed-effect models. Results Out of 245 references, a total of seven case-control studies, two cohort studies and two ecological studies were assessed in the systematic review; all studies were enrolled in the meta-analysis with the exception of the two cohort studies. No significant association has been revealed between CHDs or NTDs and neighborhood deprivation index. For CLP phenotype subgroups, we found a significantly higher rate in deprived neighborhoods (Odds Ratios (OR) = 1.22, 95% CI: 1.10, 1.36) whereas this was not significant for CP phenotype subgroups (OR = 1.20, 95%CI: 0.89, 1.61). Conclusion In spite of the small number of epidemiological studies included in the present literature review, our findings suggest that neighborhood socioeconomic level where mothers live is associated only with an increased risk of CLP phenotype subgroups. This finding has methodological limitations that impede the formulation of firm conclusions, and further investigations should confirm this association. © 2016 Deguen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
ISSN: 1932-6203

hal-01406070
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01406070
DOI : 10.1371/journal.pone.0159039
PUBMED : 27783616

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
Background: Color polymorphism in the nacre of pteriomorphian bivalves is of great interest for the pearl culture industry. The nacreous layer of the Polynesian black-lipped pearl oyster Pinctada margaritifera exhibits a large array of color variation among individuals including reflections of blue, green, yellow and pink in all possible gradients. Although the heritability of nacre color variation patterns has been demonstrated by experimental crossing, little isknown about the genes involved in these patterns. In this study, we identify a set of genes differentially expressed among extreme color phenotypes of P. margaritifera using a suppressive and subtractive hybridization (SSH) method comparing black phenotypes with full and half albino individuals.Results: Out of the 358 and 346 expressed sequence tags (ESTs) obtained by conducting two SSH libraries respectively, the expression patterns of 37 genes were tested with a real-time quantitative PCR (RT-qPCR) approach by pooling five individuals of each phenotype. The expression of 11 genes was subsequently estimated for each individual in order to detect inter-individual variation. Our results suggest that the color of the nacre is partiallyunder the influence of genes involved in the biomineralization of the calcitic layer. A few genes involved in the formation of the aragonite tablets of the nacre layer and in the biosynthesis chain of melanin also showed differential expression patterns. Finally, high variability in gene expression levels were observed within the black phenotypes.Conclusions: Our results revealed that three main genetic processes were involved in color polymorphisms: the biomineralization of the nacreous and calcitic layers and the synthesis of pigments such as melanin, suggesting that color polymorphism takes place at different levels in the shell structure. The high variability of gene expression found within black phenotypes suggests that the present work should serve as a basis for future studies exploringmore thoroughly the expression patterns of candidate genes within black phenotypes with different dominant iridescent colors.
ISSN: 1471-2164

hal-01260141
https://hal.archives-ouvertes.fr/hal-01260141
https://hal.archives-ouvertes.fr/hal-01260141/document
https://hal.archives-ouvertes.fr/hal-01260141/file/Lemer-2015-BMCGenom-Identification.pdf
DOI : 10.1186/s12864-015-1776-x

Résumé : Nous avons étudié les marqueurs hémorhéologiques, hématologiques et biochimiques chez des sujets drépanocytaires homozygotes SS (HbS/HbS) et hétérozygotes composites SC (HbS/HbC) dans deux cohortes, pédiatriques et adultes, de patients drépanocytaires, et ce, à travers 7 complications récurrentes de la drépanocytose : 2 appartenant au profil hémolytique (l’ulcère de jambes et la glomérulopathie) et 5 appartenant au phénotype visqueux/vaso-occlusif (l’hypertension artérielle, le syndrome thoracique aigu (STA), la crise vaso-occlusive (CVO), la rétinopathie et l’ostéonécrose). Nous avons montré que : 1) une viscosité sanguine et une déformabilité érythrocytaire élevées sont des facteurs de risques de CVO chez les enfants homozygotes ; 2) Une viscosité sanguine élevée est associée à une hypertension artérielle systémique relative chez des adultes SS ; 3) les enfants SC présente une fonction vasculaire mieux préservée que les enfants SS pour faire face à une augmentation de la viscosité sanguine ; 4) les patients adultes SS avec une ostéonécrose présentent une déformabilité érythrocytaire plus élevée que les patients sans ostéonécrose ; 5) une viscosité sanguine élevée est associée à la présence d’une rétinopathie chez les adultes SC mais pas chez les SS ; 6) les patients adultes SS présentant une glomérulopathie ont un taux d’hémolyse élevé, une déformabilité érythrocytaire réduite et des agrégats érythrocytaires très robustes ; 7) les patients adultes SS avec des ulcères de jambes récurrents ont un taux d’hémolyse accru et une déformabilité érythrocytaire réduite. De plus, nos travaux confirment que l’-thalassémie module les propriétés de déformabilité érythrocytaire, mais montrent pour la première fois qu’elle module aussi les propriétés d’agrégation érythrocytaire, et notamment la force des agrégats érythrocytaires. En conclusion, ces travaux permettent de préciser le rôle de la rhéologie sanguine dans un certain nombre de complications de la drépanocytose et d’enrichir le modèle préexistant divisant les complications de la drépanocytose selon 2 phénotypes : hémolytique versus visqueux/vaso-occlusif. Nous montrons pour la première fois que le phénotype hémolytique est caractérisé aussi par des anomalies de la rhéologie du globule rouge : rigidité accrue et agrégats érythrocytaire robustes.
Hemorheological, hemathological, and biochemical marquers of patients with sickle cell anemia (SS) and patients with sickle cell SC disease (SC) were studied in 2 cohorts: children and adults. We focused on 7 recurrent complications: 5 belonging to the viscosity/vaso-occlusion phenotype (systemic hypertension, acute chest syndrome (ACS), vaso-occlusive crisis (VOC), retinopathy and osteonecrosis) and 2 belonging to the hemolytic phenotype (leg ulcer and glomerulopathy). Our results show that 1) high viscosity is associated with increased risk for VOC in SS children; 2) blood viscosity is increased in SS adults with systemic relative hypertension; 3) SC children have preserved vascular function compared to SS children; 4) SS adults with osteonecrosis are characterized by higher red blood cell (RBC) deformability than SS adults without osteonecrosis; 5) high blood viscosity is associated with retinopathy in SC adults but not in SS adults; 6) SS adults affected by glomerulopathy have high hemolytic rate, low RBC deformability and increased RBC aggregates strenght; 7) SS adults with recurrent leg ulcers have high hemolytic rate and reduced RBC deformability. Moreover, our studies shows that alpha-thalassemia modulate RBC deformability and RBC aggregation properties. In conclusion, this work shows for the first time that the hemolytic phenotype is characterized by an abnormal RBC rheology which may play a role in several sickle cell complications.

http://www.theses.fr/2013AGUY0684/document

Éditeur(s) : HAL CCSD
Résumé : In Martinique in the eighteenth century, the "free people of color", both those free by birth and freedmen, black or mixed race, form a legal category, which was distinct from those of whites and slaves. Comparative studies with Spanish or English territories show that no legal regulation formalized a shift - from the category of free colored people to that of White - in the French colonies between the late seventeenth century and the French Revolution. Also, this thesis proposes to show the informal process that enabled some people - the "assimilated" - to cross the color barrier. I analysed the color prejudice, a racist system, whose ideology, supported by local regulations, legitimized the collective construction of a public and social order. In a second step, I examined the development of the color bar. The free colored people were the first to bear the brunt of the impermeability of the demarcation line and of the problems posed by the purity of blood; but some whites, through interracial unions, and Native Americans have also been targeted. Finally I thought about what made the whiteness, and the strategies to achieve whiteness, change in status. Notarial acts and 33,000 acts of parish registers treaties led to the reconstitution of genealogies, in order to examine individuals and families over generations; I observed the importance of the phenotype, whitening, legitimacy relations, privileged partners, choice of networks, wealth levels and the use of space.
À la Martinique au XVIIIe siècle, les « libres de couleur », qu’ils soient nés libres ou affranchis, noirs ou métis, forment une catégorie juridique distincte des Blancs et des esclaves. L’étude comparée, avec les territoires espagnols ou anglais, montre qu’aucune réglementation légale n’a officialisé un passage de la catégorie Libre de couleur à celle de Blanc dans les colonies françaises de la fin du XVIIe siècle à la Révolution française. Aussi, cette thèse se propose de montrer les processus officieux qui ont permis à certaines personnes – les « assimilés » – de franchir la barrière de couleur. Une réflexion a été menée sur le préjugé de couleur, système raciste dont l’idéologie, soutenue par la réglementation locale, a légitimé la construction collective d’un ordre public et social. Puis, on a examiné l’élaboration de la barrière de couleur. Les libres de couleur ont été les premiers à faire les frais de l’imperméabilisation de la ligne de démarcation et des problèmes posés par la pureté de sang ; mais les Blancs mésalliés, dans le cadre d’unions interraciales, et les Amérindiens ont aussi été visés. Enfin nous avons réfléchi à ce qui faisait la blancheur et aux stratégies adoptées pour réussir ce changement de statut. Le notariat et les 33 000 actes des registres paroissiaux traités ont donné lieu à la reconstitution de généalogies pour examiner des individus et des familles sur plusieurs générations ; on a ainsi observé l’importance du phénotype, le blanchiment, la légitimité des relations, les conjoints privilégiés, le choix des réseaux, les niveaux de fortune et l’usage de l’espace.
https://tel.archives-ouvertes.fr/tel-01221063

NNT : 2015AGUY0847
tel-01221063
https://tel.archives-ouvertes.fr/tel-01221063
https://tel.archives-ouvertes.fr/tel-01221063/document
https://tel.archives-ouvertes.fr/tel-01221063/file/These_Pierre-Louis.pdf

Éditeur(s) : HAL CCSD Instituto Oswaldo Cruz, Ministério da Saúde
Résumé : International audience
Leishmania are protozoan parasites that show remarkable diversity, as revealed by the various clinical forms of leishmaniasis, which can range from mild skin lesions to severe metastatic cutaneous/mucosal lesions. The exact nature and extent of Leishmania phenotypic diversity in establishing infection is not fully understood. In order to try to understand some aspects of this diversity, we subcutaneously infected BALB/c mice with first and second generation subclones of a L. amazonensis strain isolated from a patient (BA125) and examined in vivo lesion growth rate and antimony susceptibility. In vivo fast-, medium- and slow-growing subclones were obtained; moreover, fast-growing subclones could generate slow-growing subclones and inversely, revealing the continuous generation of diversity after passage into mice. No antimony-resistant subclone appeared, probably a rare occurrence. By tagging subclone cells with a L. amazonensis genomic cosmid library, we found that only a very small number of founding cells could produce lesions. Leishmania clones transfected with in vivo selected individual cosmids were also diverse in terms of lesion growth rate, revealing the cosmid-independent intrinsic characteristics of each clone. Our results suggest that only a few of the infecting parasites are able to grow and produce lesions; later, within the cell mixture of each lesion, there coexist several parasite populations with different potentialities to grow lesions during the next infection round. This may reflect a sort of programmed heterogeneity of individual parasites, favoring the survival of some individuals in various environmental conditions.
ISSN: 0074-0276

hal-01489009
https://hal-univ-perp.archives-ouvertes.fr/hal-01489009

Éditeur(s) : HAL CCSD
Résumé : International audience
BACKGROUND AND AIM: The impact of basal core promoter (BCP) and precore (PC) mutants of the hepatitis B virus (HBV) on liver disease severity remains controversial. The aim of the present study was to screen BCP and PC mutations in 252 HBV surface antigen (HBsAg) positive carriers in France and to assess relationships between these mutations and severe fibrosis. METHODS: Direct sequencing of the precore/core gene was used to detect A1762T/G1764A and G1757A mutations in the BCP and G1896A and G1899A mutations in the PC region. RESULTS: The prevalences of A1762T/G1764A, G1757A, G1896A, and G1899A mutations were 34.1%, 38.7%, 54.9%, and 29.3% (P < 0.001), respectively. The independent predictors of severe fibrosis (>/=F3 Metavir) were older age (P < 0.001), male gender (P = 0.012), elevated alanine aminotransferase (P < 0.001), and the double A1762T/G1764A mutant with no other mutations (P = 0.011). Interestingly, the association of the G1899A mutation with the double A1762T/G1764A mutant significantly counteracted the deleterious effect of the sole double A1762T/G1764A mutant (odds ratio [OR] = 0.28 vs. OR = 3.55, respectively, P = 0.028). CONCLUSIONS: Patients with the A1762T/G1764A mutation have a higher risk of severe fibrosis. The G1899A mutation is a protective factor against severe fibrosis that counteracted the deleterious effect of the A1762T/G1764A mutation. Finally, host phenotypic and HBV genotypic markers independently predict fibrosis severity.
Journal of gastroenterology and hepatology

hal-01477209
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01477209
DOI : 10.1111/jgh.13338
PUBMED : 26992056

Résumé : As the emergence of new vibriosis in the European Atlantic coasts has been associated with mass mortalities of molluscs cuasing important economic losses, the project obectives are to provide knowledge and operational tools to evaluate the impact of vibriosis on farmed japenese oyster Crassostrea gigas. Facing the diversity of Vibrio species associated to bivalve disease outbreaks, the difficulties of identification and the detemrination of their pathogenic abilities we propose a double approach to correlate phenotype/geneotype of a bacteria with risk of disease : 1) by genotyping we will evaluate if specific strains are associated with disease. 2) by evaluating likely virulence mechanisms implicated in pathogenesis, we will characterise the genes involved. Therefore, new diagnostic test should be used in an epizootiological study to evaluate the importance of these emerging pathogens in farmed bivalves and will be supplied for further exploitation in aquaculture.
Les vibrioses sont les infections bactériennes les plus courantes chez les espèces marines d'intérêt aquacole. Certaines espèces sont pathogènes et ont été associées à d'importantes pertes économiques pour l'industrie aquacole dans le monde. L'objectif principal de mon projet de recherche est de développer des outils diagnostiques pertinents permettant d'évaluer l'impact des vibrioses dans des élevages d'huîtres creuses Crassostrea gigas. Le problème majeur est l'extraordinaire diversité des espèces appartenant à ce genre bactérien, compliquant considérablement leur caractérisation en terme de spéciation et de virulence. Nous développons une double approche pour corréler le phénotype et le génotype de pathogènes potentiels par : 1) une clarification taxonomique des souches de vibrions nous déterminons si certaines espèces sont systématiquement associées à de maladies; 2) une caractérisation des mécanismes de virulence, nous recherchons les gènes supports de la pathogénie. Les marqueurs génétiques ou de virulence mis au point pourront alors être utilisés pour une étude épidémiologique de ces maladies.

Droits : info:eu-repo/semantics/openAccess
http://archimer.ifremer.fr/doc/2004/these-3699.pdf
http://archimer.ifremer.fr/doc/00000/3699/

Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : International audience
Treacher Collins/Franceschetti syndrome (TCS; OMIM 154500) is a disorder of craniofacial development belonging to the heterogeneous group of mandibulofacial dysostoses. TCS is classically characterized by bilateral mandibular and malar hypoplasia, downward-slanting palpebral fissures, and microtia. To date, three genes have been identified in TCS:,TCOF1, POLR1D, and POLR1C. We report a clinical and extensive molecular study, including TCOF1, POLR1D, POLR1C, and EFTUD2 genes, in a series of 146 patients with TCS. Phenotype-genotype correlations were investigated for 19 clinical features, between TCOF1 and POLR1D, and the type of mutation or its localization in the TCOF1 gene. We identified 92/146 patients (63%) with a molecular anomaly within TCOF1, 9/146 (6%) within POLR1D, and none within POLR1C. Among the atypical negative patients (with intellectual disability and/or microcephaly), we identified four patients carrying a mutation in EFTUD2 and two patients with 5q32 deletion encompassing TCOF1 and CAMK2A in particular. Congenital cardiac defects occurred more frequently among patients with TCOF1 mutation (7/92, 8%) than reported in the literature. Even though TCOF1 and POLR1D were associated with extreme clinical variability, we found no phenotype-genotype correlation. In cases with a typical phenotype of TCS, 6/146 (4%) remained with an unidentified molecular defect.
ISSN: 1098-3600

hal-01134364
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01134364
DOI : 10.1038/gim.2015.29
PUBMED : 25790162

Éditeur(s) : HAL CCSD Society for the Study of Reproduction
Résumé : International audience
Spermmotility notably depends on the structural integrity of the flagellum and the regulation ofmicrotubule dynamics. Although researchers have started to use " omics" techniques to characterize the human sperm's molecular landscape, the constituents responsible for the assembly, organization, and dynamics of the flagellum microtubule have yet to be fully defined. In this study, we defined a core set of 116 gene products associated with the human sperm microtubulome (including products potentially involved in abnormal ciliary phenotypes and male infertility disorders). To this end, we designed and applied an integrated genomics workflow and combined relevant proteomics, transcriptomics, and interactomics datasets to reconstruct a dynamic interactome map. By further integrating phenotypic information, we defined a disease-interaction network; this enabled us to highlight a number of novel factors potentially associated with altered sperm motility and male fertility. Lastly, we experimentally validated the expression pattern of two candidate genes (CUL3 and DCDC2C) that had never previously been associated with male germline differentiation. Our analysis suggested that CUL3 and DCDC2C's products have important roles in the sperm flagellum. Taken as a whole, our results demonstrate that an integrated genomics strategy can highlight relevant molecular factors in specific sperm components. This approach could be easily extended by including other " omics" data (from asthenozoospermic men, for example) and identifying other critical proteins from the human sperm microtubulome. Summary Sentence Although researchers have started to use "omics" techniques to characterize the human sperm's molecular landscape, the constituents responsible for the assembly, organization, and dynamics of the flagellum microtubule have yet to be fully defined.
ISSN: 0006-3363

hal-01515563
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01515563
DOI : 10.1095/biolreprod.116.143479
PUBMED : 28395323