Éditeur(s) : Physiomar 08 Physilogical aspects of reproduction, nutrition and growth "Marine molluscs in a changing environment"
Résumé : Bonamiosis is a parasitic disease (causative agent: Bonamia ostreae) affecting the European flat oyster Ostrea edulis, responsible for a drastic decline in the aquaculture production of this oyster species. Therefore a selective breeding program for resistance to bonamiosis has been undertaken since 1985 bu Ifremer, leading to the production of several selected oyster families. In the present study, a 6-month cohabitation challenge experiment was performed in order to transmit the disease from wild oysters (injected with the parasite) to two tested families of oysters originating from the selective breeding program. Mortalities were checked daily, and ventricular heart smears were performed on dying or moribund oysters to detect the level of infection to B. ostreae. The first infections occurred after 4 months of challenge in the tested oysters (Family 1 and Family 2). The cumulative mortalities after 5 monts were 58% for the wil oysters, 9% for Family 1 (20-month old at the beginning of the experiment) and 20% for Family 2 (8-month, old). The parasite could be detected in 66.8% of the dying wild oysters, 67.5% of the dying oysters of Family 1, 89% of the dying oysters of Family 2 and only 11% of the surviving oysters of Family 2. The mortality was significantly higher in Family 2 thant in Family 1 (x2= 20.87, p<0.001, d.f.) as well as the level of infection by the parasite found in heart smear (x2=24.34, p<0.001, 4 d.f.). This result demonstrates that prespawning oysters as yong as 1 year-old can become infected with the parasite and die from bonamiosis. This result is inconsistent with the commonly accepted critical age of 2 years-old for the disease development. The most probable cause of the dscrepancy in the development of bonamiosis between the 2 tested families is a difference in genetic background.

Droits : info:eu-repo/semantics/openAccess
http://archimer.ifremer.fr/doc/2008/acte-4535.pdf
http://archimer.ifremer.fr/doc/00000/4535/

Éditeur(s) : HAL CCSD Elsevier
Résumé : We report a preliminary analysis on the relationships between drainage basin structure and genetic structure of populations of the European vector of fasciolosis, Galba truncatula. In the study area, 251 snails belonging to 12 populations were collected along different ditches of a same river network. Each snail was genotyped at six variable microsatellite loci. Our results show that all sample sites are characterized by a low level of polymorphism and a very high and significant heterozygote deficiency. Our data reveal a significant genetic differentiation, even at a small scale, and failed to delimit clear patterns of isolation by euclidian distance. Our study shows that genetic differentiation significantly increases with hydrographic distance along the streams (p < 0.002), in consistence with the hypothesis that dispersion along the stream is dependent on the direction of water flow. This study shows that relationships can exist between the organization of the hydrological network and population biology of a disease vector, which has strong potential applications to drainage network management issues.
ISSN: 1567-1348

hal-00496374
https://hal.archives-ouvertes.fr/hal-00496374
DOI : 10.1016/j.meegid.2010.01.005

Éditeur(s) : EDP Sciences
Résumé : Bonamiosis is a parasitic disease (causative agent: Bonamia ostreae) affecting the European flat oyster Ostrea edulis, responsible for a drastic decline in its aquaculture production. Selective breeding programs for resistance to bonamiosis have been undertaken to counter this disease. In the present study, a 6-month cohabitation challenge experiment was performed in order to transmit the disease from wild oysters injected with the parasite to two tested families of oysters (20 and 8-month old at the beginning of the experiment, with different genetic backgrounds) originating from a selective breeding program developed by IFREMER in France. Mortalities were checked daily and ventricular heart smears were performed on dying or moribund oysters to detect the level of infection by B. ostreae. Mortality started after 4 months of cohabitation in the tested oysters. The cumulative mortalities after 6 months were 58% for the wild oysters, 9% for Family 1 (20-month old) and 20% for Family 2 (8-month old). In the dying oysters, the parasite could be detected in 67% of the wild oysters, 68% of Family 1 and 89% of Family 2. It was detected in only 11% of the surviving oysters of Family 2. The mortality and the level of infection by the parasite were significantly higher in Family 2 than in Family 1. Our results demonstrate that prespawning oysters as young as 1 year-old can become infected with the parasite and, most importantly, can die from bonamiosis. This result is inconsistent with the commonly accepted critical age of 2 years-old for the disease development. Additionally, no clear relationship between shell length and level of infection was observed. We also review the different methods for infection of the European flat oyster O. edulis with B. ostreae under experimental conditions and their main results.
La bonamiose est une maladie parasitaire (agent causal : Bonamia ostreae) affectant l'huître plate européenne Ostrea edulis, responsable d'un déclin drastique de sa production aquacole. Des programmes de sélection pour la résistance à la bonamiose ont été entrepris pour contrer cette maladie. Dans cette étude, une expérience de 6 mois d'infection par cohabitation a été réalisée de manière à transmettre la maladie à partir d'huîtres sauvages injectées avec le parasite vers deux familles testées d'huîtres (âgées de 20 et 8 mois en début d'expérience, avec des origines génétiques différentes) issues du programme de sélection développé par IFREMER en France. Les mortalités ont été vérifiées quotidiennement et des frottis de coeur ventriculaire réalisés sur les huîtres mortes ou moribondes pour détecter le niveau d'infection par B. ostreae. La mortalité a commencé chez les huîtres testées après 4 mois de cohabitation. Les mortalités cumulées après 6 mois étaient de 58 % chez les huîtres sauvages, 9 % chez la Famille 1 (âgées de 20 mois) et 20 % chez la Famille 2 (âgées de 8 mois). Chez les huîtres mourantes, le parasite a pu être détecté chez 67 % des huîtres sauvages, 68 % de la Famille 1 et 89 % de la Famille 2. Il n'a pu être détecté que chez 11 % des huîtres survivantes de la Famille 2. La mortalité et le niveau d'infection par le parasite étaient significativement plus élevés chez la Famille 2 que chez la Famille 1. Nos résultats démontrent que des huîtres âgées de un an peuvent devenir infectées par le parasite et surtout, peuvent mourir de bonamiose. Ce résultat contraste avec l'âge critique de développement de la maladie communément accepté de 2 ans. De plus, aucune relation claire entre la longueur de la coquille et le niveau d'infection n'a été observée. Nous faisons également la revue des différentes méthodes d'infection de l'huître plate européenne O. edulis avec B. ostreae en conditions expérimentales et leurs principaux résultats.
Aquatic Living Resources (0990-7440) (EDP Sciences), 2008-12 , Vol. 21 , P. 423-439

Droits : EDP Sciences, IFREMER, IRD 2008
http://archimer.ifremer.fr/doc/2008/publication-4783.pdf
DOI:10.1051/alr:2008053
http://archimer.ifremer.fr/doc/00000/4783/

Éditeur(s) : Université des Antilles Études caribéennes
Résumé : L’étude des représentations de la drépanocytose dans une population scolarisée de l’île de Marie-Galante (N=267), en Guadeloupe, est ici réalisée à partir du traitement des réponses à une question d’association libre qui s’inscrivait dans un questionnaire plus large. L’analyse des occurrences et des co-occurrences spontanément associées à la drépanocytose montre le flou qui entoure cette maladie dans la population étudiée, attestant d’une faible maîtrise des représentations biomédicales. Ce sont finalement le statut et la signification du sang, ainsi que la notion même de maladie génétique, qui paraissent mal assurés, car réinscrits dans l’univers des représentations culturelles et sociales liées à l’identité/altérité et à la filiation.
This paper presents a part of the results of a research on the representation on SCD (Sickle Cell Disease) among a schooled population living in Marie-Galante (Guadeloupe). It treats free associations of the respondents concerning SCD. The analysis of occurrencies and co-occurrencies spontaniously associated to the disease reveals the incertitude surrounding it, attesting thus of a small control of biomedical representations. The status and signification of blood, even as the notion of genetic disease, seem to be ambigious in their answers. They are in fact imbedded in the universe of social and cultural representations related to identity/alterity and filiation problematics.
Guadeloupe

Droits : info:eu-repo/semantics/openAccess
urn:doi:10.4000/etudescaribeennes.3684
http://journals.openedition.org/etudescaribeennes/3684

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
Background: Heterogeneous patterns of malaria transmission are thought to be driven by factors including host genetics, distance to mosquito breeding sites, housing construction, and socio-behavioural characteristics. Evaluation of local transmission epidemiology to characterize malaria risk is essential for planning malaria control and elimination programmes. The use of geographical information systems (GIS) techniques has been a major asset to this approach. To assess time and space distribution of malaria disease in Bandiagara, Mali, within a transmission season, data were used from an ongoing malaria incidence study that enrolled 300 participants aged under six years old ". Methods: Children's households were georeferenced using a handheld global position system. Clinical malaria was defined as a positive blood slide for Plasmodium falciparum asexual stages associated with at least one of the following signs: headache, body aches, fever, chills and weakness. Daily rainfall was measured at the local weather station. Landscape features of Bandiagara were obtained from satellite images and field survey. QGIS™ software was used to map malaria cases, affected and non-affected children, and the number of malaria episodes per child in each block of Bandiagara. Clusters of high or low risk were identified under SaTScan W software according to a Bernoulli model. Results: From June 2009 to May 2010, 296 clinical malaria cases were recorded. Though clearly temporally related to the rains, Plasmodium falciparum occurrence persisted late in the dry season. Two " hot spots " of malaria transmission also found, notably along the Yamé River, characterized by higher than expected numbers of malaria cases, and high numbers of clinical episodes per child. Conversely, the northeastern sector of the town had fewer cases despite its proximity to a large body of standing water which was mosquito habitat. Conclusion: These results confirm the existence of a marked spatial heterogeneity of malaria transmission in Bandiagara, providing support for implementation of targeted interventions. Background Malaria is one of the leading causes of morbidity and mortality in the world, with an estimated 3.3 billion people at risk of malaria [1]. The incidence of malaria worldwide is estimated to be 216 million cases per year, with 81% of these cases occurring in sub-Saharan Africa. Malaria kills approximately 655,000 people per year; 91% of deaths occur in sub-Saharan Africa [1], mostly in children under five years of age. In Mali, West Africa, malaria represents 36.5% of consultation motives in health center, it is a leading cause of morbidity and mortality children of less than five years of age and the first reason of anaemia in pregnant women [2]. Malaria transmission is seasonal. Malaria parasite transmission and clinical disease are characterized by important microgeographic variation, often between adjacent villages, households or families [3-8]. This local heterogeneity is driven by a variety of factors including human genetics [9,10], distance to potential breeding sites [11,12], housing construction
ISSN: 1475-2875

hal-01307672
https://hal-amu.archives-ouvertes.fr/hal-01307672
https://hal-amu.archives-ouvertes.fr/hal-01307672/document
https://hal-amu.archives-ouvertes.fr/hal-01307672/file/1475-2875-12-82.pdf
DOI : 10.1186/1476-072X-2-5

Éditeur(s) : Université de Paris 6 – Pierre et Marie Curie
Résumé : Since 1997, a new pathology seasonally occurs in new caledonian shrimp farms during the warm season and was named Summer Syndrome. Diseased Litopenaeus stylirostris shrimp suffer from a septicemic vibriosis which was attributed to V. nigripulchritudo. Preliminary studies based on a collection of V. nigripulchritudo strains have brought to light different virulence levels according to experimental infections results; three virulence statuses were defined: highly (HP), moderately (MP) and non pathogenic (NP). The aim of this work was to genetically characterize virulent V. nigripulchritudo strains. In a first step the genetic diversity of 58 V. nigripulchritudo strains was analyzed by MLST and AP-PCR, revealing a cluster of HP and MP strains, characterized by a low genetic variability and that includes all Summer Syndrome-associated isolates. This confirms the emergence of one cluster of pathogenic V. nigripulchritudo simultaneously with the emergence of the Summer Syndrome ; in a second step, 368 genetic markers of virulence were identified by a Suppressive Subtractive Hybridization performed between the genomes of a HP strain and a genetically close, NP isolate; the distribution of the screened SSH fragments was studied in 58 V. nigripulchritudo isolates by macro-array: 78 DNA fragments were selected, allowing to characterize clusters identified and pathogenic statuses; 13 are specific of the HP strains involved in Summer Syndrome. Interestingly, 10 of these markers are carried by a plasmid pSFn1 that contains sequences highly similar to those of a plasmid pAK1, detected in Vibrio shilonii, a coral pathogen. The origin and consequences of this plasmid acquisition are discussed.
Depuis 1997, les élevages de crevettes en Nouvelle-Calédonie sont confrontés à une nouvelle maladie, le Syndrome d'été, une vibriose septicémique dont l'agent étiologique est Vibrio nigripulchritudo. Les résultats d'infection expérimentale sur une collection de souches, ont montré l'existence de trois pathotypes distincts : hautement (HP), moyennement (MP) et non pathogène (NP). L'étude du polymorphisme génétique de 58 souches par typage moléculaire en MLST et AP-PCR, a mis en évidence un groupe phylogénétique particulier caractérisé par un très faible degré de variabilité génétique (confirmant l'émergence de ce groupe en parallèle à l'émergence du Syndrome d'été) et constitué uniquement de souches HP (dont toutes celles associées au Syndromed'été) et de souches MP. Afin d'identifier des marqueurs génétiques de la virulence des souches responsables du Syndrome d'été, et parmi ces marqueurs des gènes codant potentiellement pour des effecteurs de la virulence, une approche soustractive par SSH a été développée entre une souche HP de type Syndrome d'été et une souche NP : 368 marqueurs génétiques ont ainsi été mis en évidence ; la distribution de ces marqueurs a été étudiée chez les 58 souches de la collection par une approche en macroarray : 78 marqueurs ont été sélectionnés, qui permettent de caractériser les différents groupes phylogénétiques et les différents pathotypes, dont 13 fragments spécifiques des souches HP type Syndrome d'été. Parmi ces 13 fragments, 10 ont été localisés sur le plasmide pSFn1 qui a été entièrement séquencé. Ce même plasmide a été purifié uniquement des souches HP de type Syndrome d'été. Par ailleurs, une très forte homologie a été mise en évidence entre pSFn1 et pAK1, un autre plasmide également séquencé et retrouvé chez la souche V. shilonii AK1, responsable du blanchiment du corail Oculina patagonica en Méditerranée. Ces résultats ont ouvert la discussion sur le rôle de pSFn1 dans la virulence de V. nigripulchritudo.

Droits : info:eu-repo/semantics/openAccess
http://archimer.ifremer.fr/doc/2008/these-3906.pdf
http://archimer.ifremer.fr/doc/00000/3906/

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
BACKGROUND: African Americans with head and neck squamous cell carcinoma (HNSCC) have a lower survival rate than whites. This study investigated the functional importance of ancestry-informative single-nucleotide polymorphisms (SNPs) in HNSCC and also examined the effect of functionally important genetic elements on racial disparities in HNSCC survival. METHODS: Ancestry-informative SNPs, RNA sequencing, methylation, and copy number variation data for 316 oral cavity and laryngeal cancer patients were analyzed across 178 DNA repair genes. The results of expression quantitative trait locus (eQTL) analyses were also replicated with a Gene Expression Omnibus (GEO) data set. The effects of eQTLs on overall survival (OS) and disease-free survival (DFS) were evaluated. RESULTS: Five ancestry-related SNPs were identified as cis-eQTLs in the DNA polymerase beta (POLB) gene (false discovery rate [FDR]<0.01). The homozygous/heterozygous genotypes containing the African allele showed higher POLB expression than the homozygous white allele genotype (P<.001). A replication study using a GEO data set validated all 5 eQTLs and also showed a statistically significant difference in POLB expression based on genetic ancestry (P=.002). An association was observed between these eQTLs and OS (P<.037; FDR<0.0363) as well as DFS (P=.018 to.0629; FDR<0.079) for oral cavity and laryngeal cancer patients treated with platinum-based chemotherapy and/or radiotherapy. Genotypes containing the African allele were associated with poor OS/DFS in comparison with homozygous genotypes harboring the white allele. CONCLUSIONS: Analyses show that ancestry-related alleles could act as eQTLs in HNSCC and support the association of ancestry-related genetic factors with survival disparities in patients diagnosed with oral cavity and laryngeal cancer. (C) 2016 American Cancer Society.
ISSN: 0008-543X

hal-01519253
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01519253
DOI : 10.1002/cncr.30457
PUBMED : 27906459

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Purpose The purpose of this review was to examine the comprehensively accumulated data regarding potential therapeutic aspects of exogenous administration of interleukin 33 (IL-33) or its antagonists in allergic, cancerous, infectious, and inflammatory diseases. Methods A selected review was undertaken of publications that examined the protective and exacerbating effects of IL-33 or its inhibitors in different diseases. Mechanisms of action are summarized to examine the putative role of IL-33 in various diseases. Findings IL-33 promoted antibacterial, antiviral, anti-inflammatory, and vaccine adjuvant functions. However, in TH2-biased respiratory, allergic, parasitic, and inflammatory conditions, IL-33 exhibited disease-sensitizing effects. The alarmin cytokine IL-33 induced protective effects in diseases via recruitment of regulatory T cells; antiviral CD8+ cells, natural killer cells, γδ T cells, and nuocytes; antibacterial and antifungal neutrophils or macrophages; vaccine-associated B/T cells; and inhibition of nuclear factor–κB–mediated gene transcription. In contrast, IL-33 exacerbated the disease process by increasing TH2 cytokines, IgE and eosinophilic immune responses, and inhibition of leukocyte recruitment in various diseases. Implications The protective or exacerbated aspects of use of IL-33 or its inhibitors are dependent on the type of infection or inflammatory condition, duration of disease (acute or chronic), organ involved, cytokine microenvironment, dose or kinetics of IL-33, and genetic predisposition. The alarmin cytokine IL-33 acts at cellular, molecular, and transcriptional levels to mediate pluripotent functions in various diseases and has potential therapeutic value to mitigate the disease process
ISSN: 0149-2918

hal-01295637
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01295637
PUBMED : 26992663
DOI : 10.1016/j.clinthera.2016.02.021

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
Holoprosencephaly (HPE) is the most common congenital cerebral malformation, characterized by impaired forebrain cleavage and midline facial anomalies. Heterozygous mutations in 14 genes have been associated with HPE, and are often inherited from an unaffected parent underlying complex genetic bases. It is now emerging that HPE may result from a combination of multiple genetic events, rather than from a single heterozygous mutation. To explore this hypothesis, we undertook whole exome sequencing (WES) and targeted high-throughput sequencing approaches to identify mutations in HPE subjects. We report here two HPE families in which two mutations are implicated in the disease. In the first family presenting two fetuses with alobar and semi-lobar HPE, we found mutations in two genes involved in HPE, SHH and DISP1, inherited respectively from the father and the mother. The second reported case is a family with a 9-year old girl presenting lobar HPE, harbouring two compound heterozygous mutations in DISP1. Together, these cases of digenic inheritance SHH/DISP1 and autosomal recessive HPE suggest that in some families, several genetic events are necessary to cause HPE. This study highlights the complexity of HPE inheritance and has to be taken into account by clinicians to improve HPE genetic counseling.
ISSN: 0009-9163

hal-01259228
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01259228
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01259228/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01259228/file/Complex%20mode%20of%20inheritance%20in%20holoprosencephaly_accepted.pdf
DOI : 10.1111/cge.12722

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
IntroductionLeishmania RNA virus type 1 (LRV1) is an endosymbiont of some Leishmania (Vianna) species in South America. Presence of LRV1 in parasites exacerbates disease severity in animal models and humans, related to a disproportioned innate immune response, and is correlated with drug treatment failures in humans. Although the virus was identified decades ago, its genomic diversity has been overlooked until now.Methodology/Principles findingsWe subjected LRV1 strains from 19 L. (V.) guyanensis and one L. (V.) braziliensis isolates obtained from cutaneous leishmaniasis samples identified throughout French Guiana with next-generation sequencing and de novo sequence assembly. We generated and analyzed 24 unique LRV1 sequences over their full-length coding regions. Multiple alignment of these new sequences revealed variability (0.5%±23.5%) across the entire sequence except for highly conserved motifs within the 5' untranslated region. Phylogenetic analyses showed that viral genomes of L. (V.) guyanensis grouped into five distinct clusters. They further showed a species-dependent clustering between viral genomes of L. (V.) guyanensis and L. (V.) braziliensis, confirming a long-term co-evolutionary history. Noteworthy, we identified cases of multiple LRV1 infections in three of the 20 Leishmania isolates.Conclusions/SignificanceHere, we present the first-ever estimate of LRV1 genomic diversity that exists in Leishmania (V.) guyanensis parasites. Genetic characterization and phylogenetic analyses of these viruses has shed light on their evolutionary relationships. To our knowledge, this study is also the first to report cases of multiple LRV1 infections in some parasites. Finally, this work has made it possible to develop molecular tools for adequate identification and genotyping of LRV1 strains for diagnostic purposes. Given the suspected worsening role of LRV1 infection in the pathogenesis of human leishmaniasis, these data have a major impact from a clinical viewpoint and for the management of Leishmania-infected patients.
ISSN: 1935-2727

pasteur-01583523
https://hal-riip.archives-ouvertes.fr/pasteur-01583523
DOI : 10.1371/journal.pntd.0005764
PUBMED : 28715422

Résumé : The New-Caledonian shrimp industry is based on the controlled reproduction of the shrimp Litopenaeus stylirostris, a species which was introduced in the 80s. The major difficulty to which the industry has been faced for 10 years is the occurrence of the “Syndrome 93”, which corresponds to mortality phases when the temperature falls down in April-May-June. This mortality is associated to the pathogenic bacteria Vibrio penaecida. An experiment of genetic selection based on the criterion ofsurvival to Syndrome 93 has been conducted at the Laboratory of Aquaculture of New Caledonia. The 3rd selected generation had demonstrated very encouraging results (survival rates improved by around 20% in experimental infections with V. penaeicida). These results have not been confirmed at the 4th generation and no difference in terms of physiology and immunology appears between the selected population and the non-selected control population. The potential causes of these results are examined and proposals for protocol improvements are given.
La filière crevette de Nouvelle-Calédonie reposesur la maîtrise de la reproduction contrôlée de la crevette Litopenaeus stylirostris, espèce introduite dans les années 1980. La difficulté majeure que rencontre la filière depuis une dizaine d’années est la récurrence du « Syndrome 93 », qui s’exprime sous forme d’épisodes de mortalités lors des baisses de température aux intersaisons. Ces mortalités sont associées à la bactérie pathogène Vibrio penaeicida Une expérience de sélection sur un critère de survie à des épisodes de Syndrome 93 a été menée au Laboratoire Aquacole de Calédonie. La 3èmegénération sélectionnée avait montré des résultats très encourageants (survies améliorées de l’ordre de 20% lors d’infections expérimentales à V. penaeicida). Ces résultats ne sont pas confirmés en 4ème génération et aucune différence en termes physio-et immunologique n’apparaît entre la population sélectionnée et la population témoin non sélectionnée. Les causes potentielles de ces résultats sont examinées et des propositions d’amélioration de protocoles sont avancées.

Droits : 2004 Université de la Rochelle, Ifremer
http://archimer.ifremer.fr/doc/00204/31527/29943.pdf
http://archimer.ifremer.fr/doc/00204/31527/

Éditeur(s) : Styli 2003. Trente ans de crevetticulture en Nouvelle-Calédonie. Nouméa - Koné, 2-6 juin 2003. 2004. Gorarant C, Harache Y, Herbland A, Mugnier C. Ed. Ifremer, Actes de Colloque, n°38, pp.113-120
Résumé : Two oyster species are currently present along the French coasts : the indigenous European flat oyster (Ostrea edulis), and the Pacific cupped oyster (Crassostrea gigas), that has been introduced from Japan since the beginning of the 70ies. The flat oyster successively suffered from two protozoan diseases during the 60ies and its production decreased from 20 000 tons/year by that time to 1 500 tons/year nowadays. Consequently, the oyster production is principally (99%) based upon the Pacific oyster species with approximately 150 000 tons/year among which 90% are grown from the natural spat. However, the hatchery production of this species is developing and was estimated to 400 to 800 millions spat in 2002. Moreover, strengthened relationships between IFREMER and the 5 commercial hatcheries, that all joined the SYSAAF (Union of the French poultry, shellfish and fish farming selectors), allow to plan for new genetic breeding programs. At the end of the 80ies, IFREMER initiated a genetic breeding program for the resistance of the European flat oyster to the bonamiosis, and obtained strains more tolerant to this disease. After two generations of massal selection, molecular markers had identified a reduced genetic basis in this program. It was then reoriented to an intra-familial selection. However, we were confronted to a zootechnic problem to manage such a scheme and we compromised by an intra-cohorts of families selection scheme managed using molecular markers. The program has now reached the transfer level with experimentation at a professional scale. Concerning the Pacific cupped oyster, and in parallel with the obtaining and the study of polyploids, performance of different Asian cupped oyster strains were compared to the one introduced in France thirty years ago and currently suffering from summer mortalities. The local strain exhibited better performance, certainly based upon a good local adaptation. In other respects, although early growth is a relevant criteria for selection for growth to commercial stage, it is not to be privileged in the context of an oyster producing region with a limited food availability. Contrary, the spat summer mortality became a priority for numerous teams (genetic, physiology, pathology, ecology,...) joined in the MOREST program. The first results showed important survival differences between fullsib and halsib families. They indicate a genetic determinism to this character "survival" and promote for its selection.
Deux espèces d'huîtres sont aujourd'hui présentes sur les côtes françaises : l'huître plate européenne (Ostrea edulis), indigène, et l'huître creuse du Pacifique (Crassostrea gigas), introduite du Japon dans le début des années 1970. L'huître plate a subi coup sur coup, dans les années 1960, deux maladies dues à des protozoaires parasites et sa production est ainsi passée de 20 000 t/an dans les années 1960 à 1500 t/an aujourd'hui en France. Il en résulte que la filière ostréicole française repose quasiment exclusivement (99%) sur la production de l'huître creuse, C. gigas, avec 150 000 tonnes en 2000 dont environ 90% est issu du captage naturel. Cependant, la reproduction de cette espèce en écloserie est actuellement en expansion avec une estimation de 400 à 800 millions de naissains commercialisés en 2002. Des rapports renforcés entre l'IFREMER et les cinq écloseries françaises de la filière ostréicole, qui adhèrent toutes au SYSAAF (SYndicat des Sélectionneurs Avicoles et Aquacoles Français), permettent désormais d'envisager le développement de nouveaux programmes d'amélioration génétique. A la fin des années 1980, un programme de sélection pour la résistance de l'huître plate à la bonamiose a été initié au sein de l'IFREMER, et a permis d'obtenir des souches plus tolérantes à cette maladie. Après deux générations en sélection massale, les marqueurs moléculaires avaient mis en évidence une base génétique réduite au sein de ce programme qui s'était alors orienté vers une sélection intra-familiale. Devant la lourdeur zootechnique d'un tel schéma, un compromis a été trouvé en réalisant une sélection au sein de cohortes de familles biparentales, la gestion de ces cohortes étant permise par les analyses moléculaires. Le programme est maintenant dans sa phase de transfert, avec des expérimentations à plus grande échelle en partenariat avec la profession. En ce qui concerne l'huître creuse, et en parallèle de l'obtention et l'étude de polyploïdes, les performances de différentes souches d'huîtres creuses provenant d'Asie ont été comparées à celles de la souche introduite en France il y a trente ans, sujette à des mortalités estivales. La souche locale présente de meilleures performances, vraisemblablement grâce à une adaptation bien réalisée. Par ailleurs, bien que l'amélioration de la croissance jusqu'à la taille commerciale s'avère possible par une sélection précoce au stade larvaire, le critère de croissance n'est pas nécessairement à privilégier dans le contexte d'un bassin ostréicole disposant de ressources trophiques limitées. En revanche, les importantes mortalités rencontrées par le naissain en périodes estivales constituent le sujet d'étude prioritaire sur lequel se sont penchées de nombreuses équipes (génétique, physiologie, pathologie, écologie, ...) dans le cadre du grand défi MOREST. Les premiers résultats ont mis en évidence de fortes différences de survie entre des familles biparentales d'animaux indiquant un déterminisme génétique du caractère « survie », et encourageant dans la voie d'une sélection pour ce caractère.

Droits : 2004 Ifremer
http://archimer.ifremer.fr/doc/2003/acte-3491.pdf
http://archimer.ifremer.fr/doc/00000/3491/

Éditeur(s) : HAL CCSD
Résumé : International audience
Background Orodental diseases include several clinically and genetically heterogeneous disorders that can present in isolation or as part of a genetic syndrome. Due to the vast number of genes implicated in these disorders, establishing a molecular diagnosis can be challenging. We aimed to develop a targeted next-generation sequencing (NGS) assay to diagnose mutations and potentially identify novel genes mutated in this group of disorders. Methods We designed an NGS gene panel that targets 585 known and candidate genes in orodental disease. We screened a cohort of 101 unrelated patients without a molecular diagnosis referred to the Reference Centre for Oro-Dental Manifestations of Rare Diseases, Strasbourg, France, for a variety of orodental disorders including isolated and syndromic amelogenesis imperfecta (AI), isolated and syndromic selective tooth agenesis (STHAG), isolated and syndromic dentinogenesis imperfecta, isolated dentin dysplasia, otodental dysplasia and primary failure of tooth eruption. Results We discovered 21 novel pathogenic variants and identified the causative mutation in 39 unrelated patients in known genes (overall diagnostic rate: 39%). Among the largest subcohorts of patients with isolated AI (50 unrelated patients) and isolated STHAG (21 unrelated patients), we had a definitive diagnosis in 14 (27%) and 15 cases (71%), respectively. Surprisingly, COL17A1 mutations accounted for the majority of autosomal-dominant AI cases. Conclusions We have developed a novel targeted NGS assay for the efficient molecular diagnosis of a wide variety of orodental diseases. Furthermore, our panel will contribute to better understanding the contribution of these genes to orodental disease. Trial registration numbers NCT01746121 and NCT02397824
Journal of Medical Genetics

hal-01272929
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01272929
DOI : 10.1136/jmedgenet-2015-103302
PUBMED : 26502894

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 American Society for Biochemistry and Molecular Biology
Résumé : International audience
Background: We used evolutionary analysis of alkaline phosphatase (tissue nonspecific alkaline phosphatase, TNSALP) to predict missense mutations leading to hypophosphatasia. Results: We found 469 sensitive positions and validated 99% of the 204 known mutations. Conclusion: It is a more powerful method than in silico models to validate missense mutations in TNSALP. Significance: Such an approach should be widely used to support genetic diagnostics. ALPL encodes the tissue nonspecific alkaline phosphatase (TNSALP), which removes phosphate groups from various substrates. Its function is essential for bone and tooth mineralization. In humans, ALPL mutations lead to hypophosphatasia, a genetic disorder characterized by defective bone and/or tooth mineralization. To date, 275 ALPL mutations have been reported to cause hypophosphatasia, of which 204 were simple missense mutations. Molecular evolutionary analysis has proved to be an efficient method to highlight residues important for the protein function and to predict or validate sensitive positions for genetic disease. Here we analyzed 58 mammalian TNSALP to identify amino acids unchanged, or only substituted by residues sharing similar properties, through 220 millions years of mammalian evolution. We found 469 sensitive positions of the 524 residues of human TNSALP, which indicates a highly constrained protein. Any substitution occurring at one of these positions is predicted to lead to hypophosphatasia. We tested the 204 missense mutations resulting in hypophosphatasia against our predictive chart, and validated 99% of them. Most sensitive positions were located in functionally important regions of TNSALP (active site, homodimeric interface, crown domain, calcium site, ...). However, some important positions are located in regions, the structure and/or biological function of which are still unknown. Our chart of sensitive positions in human TNSALP (i) enables to validate or invalidate at low cost any ALPL mutation, which would be suspected to be responsible for hypophosphatasia, by contrast with time consuming and expensive functional tests, and (ii) displays higher predictive power than in silico models of prediction.
ISSN: 0021-9258

hal-01545479
https://hal.archives-ouvertes.fr/hal-01545479
DOI : 10.1074/jbc.M114.576843

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Hemorheological abnormalities have been well characterized in sickle cell disease (SCD) and seem to modulate the clinical severity [1]. For instance, increased blood viscosity raises the risk for frequent vaso-occlusive crisis (VOC) and increased red blood cell (RBC) aggregates robustness (i.e., RBC disaggregation threshold) enhances the risks for acute chest syndrome (ACS) [2]. Moreover, patients with the most rigid RBCs are characterized by high hemolytic rate, which increases the risks to develop leg ulcers or glomerulopathy [3]. However, except few studies supporting an effect of alpha-thalassemia and oxidative stress [1] on RBC rheological properties of SCD patients, very few experiments focused on the genetic and cellular factors modulating blood rheology in this disease.
ISSN: 1079-9796

hal-01263890
https://hal.archives-ouvertes.fr/hal-01263890
https://hal.archives-ouvertes.fr/hal-01263890/document
https://hal.archives-ouvertes.fr/hal-01263890/file/Ferdinand%20et%20al.%20eNOS%20and%20RBC%20rheology%20in%20SCD_BCMD.pdf
PUBMED : 26142331

Éditeur(s) : HAL CCSD BMJ Publishing Group
Résumé : International audience
BACKGROUND: Mutations in the leucine-rich-repeat kinase 2 (LRRK2) gene have been identified in families with autosomal dominant Parkinson's disease (ADPD), the most common of which is the p.G2019S substitution that has been found at varying frequencies worldwide. Because of the size of the LRRK2 gene, few studies have analysed the entire gene in large series of ADPD families. METHODS: We performed extensive mutation analyses of all 51 coding exons of the LRRK2 gene in index cases from 226 Parkinson's disease families compatible with autosomal dominant inheritance, mostly from France (n = 182) and North Africa (n = 14). RESULTS: We found 79 sequence variants, 29 of which were novel. Eight potentially or proven pathogenic mutations were found in 22 probands (9.7%). There were four novel amino acid substitutions that are potentially pathogenic (p.S52F, p.N363S, p.I810V, p.R1325Q) and two novel variants, p.H1216R and p.T1410M, that are probably not causative. The common p.G2019S mutation was identified in 13 probands (5.8%) including six from North Africa (43%). The known heterozygous p.R1441H and p.I1371V mutations were found in two probands each, and the p.E334K variant was identified in one single patient. Most potentially or proven pathogenic mutations were located in the functional domains of the Lrrk2 protein. CONCLUSION: This study leads us to conclude that LRRK2 mutations are a common cause of autosomal dominant Parkinson's disease in Europe and North Africa.
ISSN: 0022-2593

inserm-00529272
http://www.hal.inserm.fr/inserm-00529272
DOI : 10.1136/jmg.2008.062612
PUBMED : 19357115

Éditeur(s) : PSIC 11 - 11th Pacific Science Inter-Congress : Pacific Countries and their Ocean: Facing Local and Global Changes / 2nd Symposium on French Research in the Pacific. March 2 - 6, 2009 Tahiti, French Polynesia
Résumé : Shrimp farming in New Caledonia relies on the culture of a domesticated strain of Litopenaeus stylirostris introduced from Mexico at a time when genetic principles were of little or no consideration. Since then, advances in agriculture and for some aquatic species of importance led caledonian shrimp farmers to reconsider the appropriateness of a genetic improvement strategy adapted to local biotechnical and economical constraints. This questioning involves many different and interrelated aspects: scientific and technologic (genetics, biosecurity, quarantine, ), economic and organizational (financing, diffusion of genetic improvement) and pedagogic (awareness of farmers). Local institutions, producers associations, research centre and sanitary services associated to carry on the test of a first improvement strategy based on the crossing of different strains of L. stylirostris. This conceptually simple approach aimed at eliminating inbreeding, the first genetic limitating factor of improvement in captive populations. A second domesticated strain was obtained from Hawaii by the caledonian farmers, imported through a quarantine under the control of the zoosanitary local authorities, and reproduced and tested as pure or crossbred stocks by Ifremer within the framework of an interdisciplinary research project financed by caledonian institutions. Present results for hybrids (better growth and survival in the absence of virus) demonstrate the validity of this approach. They also bring out the importance to simultaneously integrate in a development scheme, a breeding centre to maintain and reproduce disease free breeders. This strategy and organization, tested in New Caledonia, could possibly be of benefit to other small scale aquaculture activities in the pacific islands.
La filière crevetticole de Nouvelle-Calédonie s’est développée jusqu’à aujourd’hui à partir d’un stock domestiqué de Litopenaeus stylirostris introduit d’Amérique à une époque où les principes de base en génétique n’étaient pas ou peu appliqués en aquaculture. Les avancées récentes en agriculture et chez quelques espèces aquacoles d’importance mondiale ont conduit les acteurs de cette filière à se poser la question de la mise en place d’une stratégie d’amélioration génétique adaptée aux contraintes biotechniques et économiques locales. Cette réflexion comportait à la fois des aspects scientifiques et technologiques (génétique, biosécurité, quarantaine, conservatoire), économiques et organisationnels (coût de l’opération, modalité de diffusion du progrès attendu), pédagogiques (sensibilisation des fermiers). Des acteurs d’horizons différents (institutions locales, association de producteurs, centre de recherche, police zoosanitaire) se sont associés pour monter une opération de testage d’une première stratégie d’amélioration par croisement de souches de la même espèce. Cette stratégie conceptuellement simple visait l’élimination du premier facteur génétique de limitation des performances d’élevage d’une population captive, à savoir une consanguinité d’autant plus élevée que le nombre de géniteurs fondateurs était faible. Une seconde souche domestiquée a ainsi été acquise à Hawaii par les producteurs calédoniens, contrôlée en quarantaine par les services vétérinaires calédoniens en charge de la réglementation sanitaire, reproduite et testée pure et en croisement par l’Ifremer dans le cadre d’un projet de recherche pluridisciplinaire plus large financé par les institutions du Pays. Les résultats obtenus démontrent l’intérêt de la démarche (meilleure croissance, meilleure survie en l’absence de virus). Mais ils montrent aussi l’utilité d’intégrer simultanément dans le plan de développement de la filière une stratégie de conservation des souches parentales afin de disposer de géniteurs exempts de pathogènes. Cette stratégie et cette organisation testées en Nouvelle-Calédonie pourraient vraisemblablement être profitables à d’autres filières aquacoles modestes, en particulier dans les pays insulaires du Pacifique.

Droits : info:eu-repo/semantics/openAccess
http://archimer.ifremer.fr/doc/00198/30879/29247.pdf
http://archimer.ifremer.fr/doc/00198/30879/

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
BACKGROUND: The genetic diversity of Plasmodium falciparum has been extensively studied in various parts of the world. However, limited data are available from Mauritania. The present study examined and compared the genetic diversity of P. falciparum isolates in Mauritania. METHODS: Plasmodium falciparum isolates blood samples were collected from 113 patients attending health facilities in Nouakchott and Hodh El Gharbi regions. K1, Mad20 and RO33 allelic family of msp-1 gene were determined by nested PCR amplification. RESULTS: K1 family was the predominant allelic type carried alone or in association with Ro33 and Mad20 types (90%; 102/113). Out of the 113 P. falciparum samples, 93(82.3%) harboured more than one parasite genotype. The overall multiplicity of infection was 3.2 genotypes per infection. There was no significant correlation between multiplicity of infection and age of patients. A significant increase of multiplicity of infection was correlated with parasite densities. CONCLUSIONS: The polymorphism of P. falciparum populations from Mauritania was high. Infection with multiple P. falciparum clones was observed, as well as a high multiplicity of infection reflecting both the high endemicity level and malaria transmission in Mauritania.
ISSN: 1475-2875

inserm-00936407
http://www.hal.inserm.fr/inserm-00936407
http://www.hal.inserm.fr/inserm-00936407/document
http://www.hal.inserm.fr/inserm-00936407/file/1475-2875-13-26.pdf
DOI : 10.1186/1475-2875-13-26

Éditeur(s) : HAL CCSD Frontiers Media
Résumé : The disease, Heartwater, caused by the Anaplasmataceae E. ruminantium, represents a major problem for tropical livestock and wild ruminants. Up to now, no effective vaccine has been available due to a limited cross protection of vaccinal strains on field strains and a high genetic diversity of Ehrlichia ruminantium within geographical locations. To address this issue, we inferred the genetic diversity and population structure of 194 E. ruminantium isolates circulating worldwide using Multilocus Sequence Typing based on lipA, lipB, secY, sodB, and sucA genes. Phylogenetic trees and networks were generated using BEAST and SplitsTree, respectively, and recombination between the different genetic groups was tested using the PHI test for recombination. Our study reveals the repeated occurrence of recombination between E. ruminantium strains, suggesting that it may occur frequently in the genome and has likely played an important role in the maintenance of genetic diversity and the evolution of E. ruminantium. Despite the unclear phylogeny and phylogeography, E. ruminantium isolates are clustered into two main groups: Group 1 (West Africa) and a Group 2 (worldwide) which is represented by West, East, and Southern Africa, Indian Ocean, and Caribbean strains. Some sequence types are common between West Africa and Caribbean and between Southern Africa and Indian Ocean strains. These common sequence types highlight two main introduction events due to the movement of cattle: from West Africa to Caribbean and from Southern Africa to the Indian Ocean islands. Due to the long branch lengths between Group 1 and Group 2, and the propensity for recombination between these groups, it seems that the West African clusters of Subgroup 2 arrived there more recently than the original divergence of the two groups, possibly with the original waves of domesticated ruminants that spread across the African continent several thousand years ago.
ISSN: 2235-2988

hal-01594501
https://hal.archives-ouvertes.fr/hal-01594501
https://hal.archives-ouvertes.fr/hal-01594501/document
https://hal.archives-ouvertes.fr/hal-01594501/file/paper_MLST_ER_2016_%7B51027B58-C2C7-41C8-9746-BD8A9F387C87%7D.pdf
DOI : 10.3389/fcimb.2016.00111