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 Nature Publishing Group
Résumé : International audience
The main familial focal epilepsies are autosomal dominant nocturnal frontal lobe epilepsy, familial temporal lobe epilepsy and familial focal epilepsy with variable foci. A frameshift mutation in the DEPDC5 gene (encoding DEP domain-containing protein 5) was identified in a family with focal epilepsy with variable foci by linkage analysis and exome sequencing. Subsequent pyrosequencing of DEPDC5 in a cohort of 15 additional families with focal epilepsies identified 4 nonsense mutations and 1 missense mutation. Our findings provided evidence of frequent (37%) loss-of-function mutations in DEPDC5 associated with a broad spectrum of focal epilepsies. The implication of a DEP (Dishevelled, Egl-10 and Pleckstrin) domain-containing protein that may be involved in membrane trafficking and/or G protein signaling opens new avenues for research.
ISSN: 1061-4036

hal-01544763
https://hal.archives-ouvertes.fr/hal-01544763
DOI : 10.1038/ng.2601

Éditeur(s) : HAL CCSD Société géologique de France
Résumé : International audience
In this paper, we provide the first structural map of Les Saintes archipelago (Guadeloupe, Lesser Antilles). The finite strain pattern displays four families of fault systems characterized by their statistical structural orientations: N000-N020, N050-N070, N090-N110 and N130-N140 trending fault systems. Our onshore results thus underline a fault network much more complex than the one depicted by the previous offshore geophysical investigations around Les Saintes archipelago, which show only N120-N150 trending system. According to the available K-Ar dating of the volcanic rocks and the relative chronology of the faults defined in the field, we determine the deformation history in Les Saintes islands since the last 3 Ma. The four highlighted trending fault systems are already active since the Pliocene and are consistent with the present-day extensional tectonics in the Guadeloupe archipelago compatible with the reactiva-tion of inherited structures at the active arc scale. We interpret the tectonic evolution of Les Saintes islands as the result of interplay between subduction of aseismic ridges (Tiburon and Barracuda ridges) and oblique convergence. Furthermore , we recognized an exhumed geothermal paleo-system in Terre-de-Haut island which is a good analogue of the present-day active Bouillante geothermal system. Its duration is estimated at 400 k.y. during the Pliocene.
EISSN: 1777-5817

hal-01625778
https://hal.univ-antilles.fr/hal-01625778
https://hal.univ-antilles.fr/hal-01625778/document
https://hal.univ-antilles.fr/hal-01625778/file/VeratIEtAl_Final.pdf
DOI : 10.2113/gssgfbull.187.1.3

Éditeur(s) : HAL CCSD Météo et Climat
Résumé : International audience
Les risques hydrométéorologiques sont au coeur du programme de recherche HyMeX sur le cycle de l'eau en Méditerranée. HyMeX a pour ambition d'améliorer leur prévision, de mieux connaître leur variabilité à l'échelle pluriannuelle et de renseigner sur leur évolution, dans le contexte du changement climatique. À cette fin, deux campagnes de mesures dédiées à ces événements extrêmes (SOP1 : pluies intenses et crues rapides ; SOP2 : vents forts et formation d'eaux denses) sont organisées en Méditerranée nord-occidentale, entre septembre 2012 et mars 2013.
ISSN: 0026-1181

hal-00829760
https://hal.archives-ouvertes.fr/hal-00829760
DOI : 10.4267/2042/48793

Éditeur(s) : HAL CCSD Météo et Climat
Résumé : International audience
D'initiative française, le projet international HyMeX a pour objectif d'améliorer la compréhension du cycle de l'eau en Méditerranée, de sa variabilité, de l'échelle de l'événement météorologique aux échelles saisonnières et interannuelles, et de ses caractéristiques sur une décennie, dans un contexte de changement global. Le projet est motivé par le rôle déterminant des processus de mésoéchelle, couplés entre l'atmosphère, la mer et la terre, sur la variabilité du système climatique et sur le déclenchement d'événements hydrométéorologiques extrêmes (précipitations et inondations, vents forts et convection océanique, canicules et sécheresses). Le projet vise enfin à évaluer les conséquences de ces événements extrêmes sur la vulnérabilité sociale et économique de cette région et sa capacité d'adaptation.
ISSN: 0026-1181

hal-00828758
https://hal.archives-ouvertes.fr/hal-00828758
https://hal.archives-ouvertes.fr/hal-00828758/document
https://hal.archives-ouvertes.fr/hal-00828758/file/meteo_2013_80_23%20%281%29.pdf
DOI : 10.4267/2042/48792

Éditeur(s) : HAL CCSD Wiley/Blackwell
Résumé : International audience
This article documents the addition of 512 microsatellite marker loci and nine pairs of Single Nucleotide Polymorphism (SNP) sequencing primers to the Molecular Ecology Resources Database. Loci were developed for the following species: Alcippe morrisonia morrisonia, Bashania fangiana, Bashania fargesii, Chaetodon vagabundus, Colletes floralis, Coluber constrictor flaviventris, Coptotermes gestroi, Crotophaga major, Cyprinella lutrensis, Danaus plexippus, Fagus grandifolia, Falco tinnunculus, Fletcherimyia fletcheri, Hydrilla verticillata, Laterallus jamaicensis coturniculus, Leavenworthia alabamica, Marmosops incanus, Miichthys miiuy, Nasua nasua, Noturus exilis, Odontesthes bonariensis, Quadrula fragosa, Pinctada maxima, Pseudaletia separata, Pseudoperonospora cubensis, Podocarpus elatus, Portunus trituberculatus, Rhagoletis cerasi, Rhinella schneideri, Sarracenia alata, Skeletonema marinoi, Sminthurus viridis, Syngnathus abaster, Uroteuthis (Photololigo) chinensis, Verticillium dahliae, Wasmannia auropunctata, and Zygochlamys patagonica. These loci were cross-tested on the following species: Chaetodon baronessa, Falco columbarius, Falco eleonorae, Falco naumanni, Falco peregrinus, Falco subbuteo, Didelphis aurita, Gracilinanus microtarsus, Marmosops paulensis, Monodelphis Americana, Odontesthes hatcheri, Podocarpus grayi, Podocarpus lawrencei, Podocarpus smithii, Portunus pelagicus, Syngnathus acus, Syngnathus typhle,Uroteuthis (Photololigo) edulis, Uroteuthis (Photololigo) duvauceli and Verticillium albo-atrum. This article also documents the addition of nine sequencing primer pairs and sixteen allele specific primers or probes for Oncorhynchus mykiss and Oncorhynchus tshawytscha; these primers and assays were cross-tested in both species.
ISSN: 1755-098X

hal-01094222
https://hal-agroparistech.archives-ouvertes.fr/hal-01094222
DOI : 10.1111/j.1755-0998.2010.02916.x

Éditeur(s) : HAL CCSD
Résumé : Poster
The Lesser Caucasus in Armenia is an active volcanic and tectonic zone which resulted from the collision of the Arabian and the Eurasian plates since Neogene times. The During Quaternary, Lesser Caucasus was uplifted (0.3 mm/yr; Mitchell and Westaway, 1999) and experienced extensional tectonics times. Large lakes developed in graben structures. The diatomitic sequences of the Shamb paleo-lake (South Armenia) offer a rare opportunity to give new insights of Western Asia paleo-climate. Based on macroflora analysis, Bruch and Gabrielyan (2002) proposed a cooling and drying general climate trend through Pleistocene times in relation with a general uplift of the chain. Several questions have to be answer for this poorly investigated region. Did the climate record humid glacials and arid interglacials as suggested northward in Kazakhstan? What are the vegetation and climate responses to orbital parameters and to the monsoon? Moreover the lesser Caucasus is known as the entrance way used by the first hominids in Eurasia during Pleistocene time. How was the environment at this time? We present an integrated palynological, 40Ar/39Ar isotopic and magnetostratigraphic study for the most complete section (Joannin et al., in press). 40Ar/39Ar dating of two volcaniclastic layers provided ages of 1.24 ± 0.03 and 1.16 ± 0.02 Ma (2. Magnetostratigraphic data show that the entire Shamb section is of reversed polarity which correlates with part of the Matuyama period (1.785-1.070 Ma). Pollen assemblages and macroremains diversity revealed an alternation of glacial and interglacial phases that are compared with climate changes inferred from the global isotopic curve. The Shamb section ranges from approximately 1.300 to 1.080 Ma in age (marine isotopic stages 40 to 31). The vegetation of the Lesser Caucasus developed in a mosaic pattern in a Pleistocene continental, mostly arid climate, similar to the present-day climate. The vegetation changes record a dominant climate response to the obliquity orbital parameter. The influence of precession could not be established from the Shamb data. Pollen and macroflora both indicate that glacial periods were cold and dry and that interglacials were warm with local humidity. The early Pleistocene climatic model for Western Asia is thus similar to the climatic model for the Mediterranean area. Bruch, A., Gabrielyan, I.G., 2002. Quantitative data of the Neogene climatic development in Armenia and Nakhichevan. Acta Universitatis Carolinae – Geologica 46, 41–48. Joannin, S., Cornée, J.J., Münch, P., Fornari, M., Vasiliev, J., Krijgsman, W., Nahapetyan, S., Gabrielyan, Y., Ollivier, V., Roiron, P., Chataîgnier, C. In press. Early Pleistocene climatic cycles in continental deposits of the Lesser Caucasus of Armenia inferred from palynology, magnetostratigraphy, and 40Ar/39Ar dating. Earth and Planetary Science Letters. Mitchell, J., Westaway, R., 1999. Chronology of Neogene and Quaternary uplift and magmatism in the Caucasus: constraints from K-Ar dating of volcanism in Armenia. Tectonophysics 304, 157–186.
EGU Eurasian Climate and Tectonics
Vienne, Austria

hal-00481799
https://hal.archives-ouvertes.fr/hal-00481799

Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : International audience
The etiology of congenital heart defect (CHD) combines environmental and genetic factors. So far, there were studies reporting on the screening of a single gene on unselected CHD or on familial cases selected for specific CHD types. Our goal was to systematically screen a proband of familial cases of CHD on a set of genetic tests to evaluate the prevalence of disease-causing variant identification. A systematic screening of GATA4, NKX2-5, ZIC3 and Multiplex ligation-dependent probe amplification (MLPA) P311 Kit was setup on the proband of 154 families with at least two cases of non-syndromic CHD. Additionally, ELN screening was performed on families with supravalvular arterial stenosis. Twenty-two variants were found, but segregation analysis confirmed unambiguously the causality of 16 variants: GATA4 (1 x), NKX2-5 (6 x), ZIC3 (3 x), MLPA (2 x) and ELN (4 x). Therefore, this approach was able to identify the causal variant in 10.4% of familial CHD cases. This study demonstrated the existence of a de novo variant even in familial CHD cases and the impact of CHD variants on adult cardiac condition even in the absence of CHD. This study showed that the systematic screening of genetic factors is useful in familial CHD cases with up to 10.4% elucidated cases. When successful, it drastically improved genetic counseling by discovering unaffected variant carriers who are at risk of transmitting their variant and are also exposed to develop cardiac complications during adulthood thus prompting long-term cardiac follow-up. This study provides an important baseline at dawning of the next-generation sequencing era.
ISSN: 1018-4813

hal-01404211
https://hal-univ-bourgogne.archives-ouvertes.fr/hal-01404211
DOI : 10.1038/ejhg.2015.105
PUBMED : 26014430

Éditeur(s) : HAL CCSD Wiley/Blackwell
Résumé : International audience
Photosynthetic eukaryotes have a critical role as the main producers in most ecosystems of the biosphere. The ongoing environmental metabarcoding revolution opens the perspective for holistic ecosystems biological studies of these organisms, in particular the unicellular microalgae that often lack distinctive morphological characters and have complex life cycles. To interpret environmental sequences, metabarcoding necessarily relies on taxonomically curated databases containing reference sequences of the targeted gene (or barcode) from identified organisms. To date, no such reference framework exists for photosynthetic eukaryotes. In this study, we built the PhytoREF database that contains 6490 plastidial 16S rDNA reference sequences that originate from a large diversity of eukaryotes representing all known major photosynthetic lineages. We compiled 3333 amplicon sequences available from public databases and 879 sequences extracted from plastidial genomes, and generated 411 novel sequences from cultured marine microalgal strains belonging to different eukaryotic lineages. A total of 1867 environmental Sanger 16S rDNA sequences were also included in the database. Stringent quality filtering and a phylogeny-based taxonomic classification were applied for each 16S rDNA sequence. The database mainly focuses on marine microalgae, but sequences from land plants (representing half of the PhytoREF sequences) and freshwater taxa were also included to broaden the applicability of PhytoREF to different aquatic and terrestrial habitats. PhytoREF, accessible via a web interface (http://phytoref.fr), is a new resource in molecular ecology to foster the discovery, assessment and monitoring of the diversity of photosynthetic eukaryotes using high-throughput sequencing.
ISSN: 1755-098X

hal-01149047
http://hal.upmc.fr/hal-01149047
http://hal.upmc.fr/hal-01149047/document
http://hal.upmc.fr/hal-01149047/file/Decelle_2015_PhytoREF.pdf
DOI : 10.1111/1755-0998.12401

Éditeur(s) : HAL CCSD MDPI
Résumé : International audience
Lead in childhood is well known to be associated with poor neurodevelopment. As part of a study on maternal anemia and offspring neurodevelopment, we analyzed blood lead level (BLL) with no prior knowledge of lead exposure in 225 mothers and 685 offspring 1 to 2 years old from Allada, a semi-rural area in Benin, sub-Saharan Africa, between May 2011 and May 2013. Blood samples were analyzed by inductively coupled plasma mass spectrometry. Environmental assessments in households and isotopic ratio measurements were performed for eight children with BLL extgreater 100 µg/L. High lead levels (BLL extgreater 50 µg/L) were found in 44% of mothers and 58% of children. The median BLL was 55.1 (interquartile range 39.2-85.0) and 46.6 (36.5-60.1) µg/L, respectively. Maternal BLL was associated with offspring's consumption of piped water and animals killed by ammunition. Children's BLL was associated with presence of paint chips in the house and consumption of animals killed by ammunition. In this population, with 98% of children still breastfed, children's BLL was highly associated with maternal BLL on multivariate analyses. Environmental measures and isotopic ratios supported these findings. Offspring may be highly exposed to lead in utero and probably via breastfeeding in addition to lead paint exposure
ISSN: 1660-4601

hal-01296778
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01296778
DOI : 10.3390/ijerph13030316
PUBMED : 26978384

Éditeur(s) : HAL CCSD Société géologique de France
Résumé : International audience
EISSN: 1777-5817

hal-01672822
https://hal-amu.archives-ouvertes.fr/hal-01672822
DOI : 10.1051/bsgf/2017183