Molecular Diagnosis of Neonatal Diabetes Mellitus Using Next-Generation Sequencing of the Whole Exome

Background: Accurate molecular diagnosis of monogenic non-autoimmune neonatal diabetes mellitus (NDM) is critical for patient care, as patients carrying a mutation in KCNJ11 or ABCC8 can be treated by oral sulfonylurea drugs instead of insulin therapy. This diagnosis is currently based on Sanger sequencing of at least 42 PCR fragments from the KCNJ11, ABCC8, and INS genes. Here, we assessed the feasibility of using the next-generation whole exome sequencing (WES) for the NDM molecular diagnosis. Methodology/Principal Findings: We carried out WES for a patient presenting with permanent NDM, for whom mutations in KCNJ11, ABCC8 and INS and abnormalities in chromosome 6q24 had been previously excluded. A solution hybridization selection was performed to generate WES in 76 bp paired-end reads, by using two channels of the sequencing instrument. WES quality was assessed using a high-resolution oligonucleotide whole-genome genotyping array. From our WES with high-quality reads, we identified a novel non-synonymous mutation in ABCC8 (c.1455G.C/p.Q485H), despite a previous negative sequencing of this gene. This mutation, confirmed by Sanger sequencing, was not present in 348 controls and in the patient’s mother, father and young brother, all of whom are normoglycemic. Conclusions/Significance: WES identified a novel de novo ABCC8 mutation in a NDM patient. Compared to the current Sanger protocol, WES is a comprehensive, cost-efficient and rapid method to identify mutations in NDM patients. W

A comprehensive assessment of somatic mutation detection in cancer using whole-genome sequencing.

As whole-genome sequencing for cancer genome analysis becomes a clinical tool, a full understanding of the variables affecting sequencing analysis output is required. Here using tumour-normal sample pairs from two different types of cancer, chronic lymphocytic leukaemia and medulloblastoma, we conduct a benchmarking exercise within the context of the International Cancer Genome Consortium. We compare sequencing methods, analysis pipelines and validation methods. We show that using PCR-free methods and increasing sequencing depth to ∼ 100 × shows benefits, as long as the tumour:control coverage ratio remains balanced. We observe widely varying mutation call rates and low concordance among analysis pipelines, reflecting the artefact-prone nature of the raw data and lack of standards for dealing with the artefacts. However, we show that, using the benchmark mutation set we have created, many issues are in fact easy to remedy and have an immediate positive impact on mutation detection accuracy.We thank the DKFZ Genomics and Proteomics Core Facility and the OICR Genome Technologies Platform for provision of sequencing services. Financial support was provided by the consortium projects READNA under grant agreement FP7 Health-F4-2008-201418, ESGI under grant agreement 262055, GEUVADIS under grant agreement 261123 of the European Commission Framework Programme 7, ICGC-CLL through the Spanish Ministry of Science and Innovation (MICINN), the Instituto de Salud Carlos III (ISCIII) and the Generalitat de Catalunya. Additional financial support was provided by the PedBrain Tumor Project contributing to the International Cancer Genome Consortium, funded by German Cancer Aid (109252) and by the German Federal Ministry of Education and Research (BMBF, grants #01KU1201A, MedSys #0315416C and NGFNplus #01GS0883; the Ontario Institute for Cancer Research to PCB and JDM through funding provided by the Government of Ontario, Ministry of Research and Innovation; Genome Canada; the Canada Foundation for Innovation and Prostate Cancer Canada with funding from the Movember Foundation (PCB). PCB was also supported by a Terry Fox Research Institute New Investigator Award, a CIHR New Investigator Award and a Genome Canada Large-Scale Applied Project Contract. The Synergie Lyon Cancer platform has received support from the French National Institute of Cancer (INCa) and from the ABS4NGS ANR project (ANR-11-BINF-0001-06). The ICGC RIKEN study was supported partially by RIKEN President’s Fund 2011, and the supercomputing resource for the RIKEN study was provided by the Human Genome Center, University of Tokyo. MDE, LB, AGL and CLA were supported by Cancer Research UK, the University of Cambridge and Hutchison-Whampoa Limited. SD is supported by the Torres Quevedo subprogram (MI CINN) under grant agreement PTQ-12-05391. EH is supported by the Research Council of Norway under grant agreements 221580 and 218241 and by the Norwegian Cancer Society under grant agreement 71220-PR-2006-0433. Very special thanks go to Jennifer Jennings for administrating the activity of the ICGC Verification Working Group and Anna Borrell for administrative support.This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/ncomms1000

Vocabulaire de la création d’entreprise par essaimage

« Les langues vivantes se modifient en synergie avec leur environnement, avec les découvertes, les innovations, les transformations économiques et sociales. La langue française se modifie et s'enrichit au rythme de l'évolution des modalités de création d'entreprise, et il nous incombe à tous de suivre cette transformation dans un esprit innovateur et progressiste. » — La directrice générale adjointe des services linguistiques de l'Office québécois de la langue française, Danielle Turcotte Ce livre présente : • Les concepts et les termes fondamentaux de la création d'entreprise par essaimage • La terminologie de la restructuration par scission • Un lexique bilingue français-anglai

La problématique éthique du développement de l’aquaculture industrielle au Canada : analyse mésologique d’un nouveau rapport possible à l’océan

Aquaculture development in Canada is a recent and important phenomenon. As an economic activity, aquaculture has the potential to compensate for the rapid loss of marine resources that have made the country’s reputation for centuries. But the development of aquaculture farms and the possibility to introduce new biotechnological techniques and products – such as the transgenic salmon – has provoked social opposition from various organizations and interest groups directed towards the investors and promoters of this new industry. This article aims at analyzing, from an ethical perspective, the possibilities of aquaculture in this context. The method involved is inspired from a « mesology », meaning that it focuses primarily on the human beings’ relation to nature. We argue that the development of aquaculture in Canada could be a beneficial strategy because it creates new places of contact between men and nature through a relation of domestication. Nevertheless, the introduction of high-tech methods such as transgenic manipulations can reduce the quality and the diversity of these relations because they are essentially modern techniques

La création d’entreprise par essaimage

1 aides personnalisées n. f. pl. personnalized assistance Concours qui est prêté à un salarié-essaimeur en fonction de ses besoins particuliers dans sa démarche de création d’entreprise. note Les aides personnalisées peuvent être psychologiques, administratives, commerciales, logistiques et financières. 2 cellule de soutien à l’essaimage n. f. synonyme cellule ..

La problématique éthique du développement de l’aquaculture industrielle au Canada : analyse mésologique d’un nouveau rapport possible à l’océan

Le développement des techniques d’aquaculture au Canada est un phénomène qui a récemment pris une importance considérable. Au plan économique, ces techniques de production peuvent potentiellement combler un vide laissé par la baisse des stocks naturels de poissons qui faisaient la réputation du pays. Mais au plan social, l’apparition des fermes de production aquacole et la possibilité de mettre en oeuvre des technologies de transgénèse pour en augmenter la productivité ont provoqué des conflits importants entre les promoteurs et d’autres groupes d’intérêts. Cet article vise à faire une analyse éthique des possibilités qu’offre l’aquaculture au Canada dans le contexte actuel. La méthode d’analyse s’inspire d’une approche mésologique, c’est-à-dire que le centre d’intérêt est la relation de l’être humain à la nature. Nous soutenons que le développement des fermes d’aquaculture au Canada peut être une stratégie bénéfique parce qu’il ouvre la voie à la création de lieux de rencontre entre l’être humain et la nature à travers une relation de domestication. Toutefois, la mise en oeuvre de techniques de pointe telle que la transgénèse menace de réduire la qualité et la diversité des relations instituées parce que ces techniques sont essentiellement des techniques modernes.Aquaculture development in Canada is a recent and important phenomenon. As an economic activity, aquaculture has the potential to compensate for the rapid loss of marine resources that have made the country’s reputation for centuries. But the development of aquaculture farms and the possibility to introduce new biotechnological techniques and products – such as the transgenic salmon – has provoked social opposition from various organizations and interest groups directed towards the investors and promoters of this new industry. This article aims at analyzing, from an ethical perspective, the possibilities of aquaculture in this context. The method involved is inspired from a « mesology », meaning that it focuses primarily on the human beings’ relation to nature. We argue that the development of aquaculture in Canada could be a beneficial strategy because it creates new places of contact between men and nature through a relation of domestication. Nevertheless, the introduction of high-tech methods such as transgenic manipulations can reduce the quality and the diversity of these relations because they are essentially modern techniques

La problématique éthique du développement de l’aquaculture industrielle au Canada : analyse mésologique d’un nouveau rapport possible à l’océan

Aquaculture development in Canada is a recent and important phenomenon. As an economic activity, aquaculture has the potential to compensate for the rapid loss of marine resources that have made the country’s reputation for centuries. But the development of aquaculture farms and the possibility to introduce new biotechnological techniques and products – such as the transgenic salmon – has provoked social opposition from various organizations and interest groups directed towards the investors and promoters of this new industry. This article aims at analyzing, from an ethical perspective, the possibilities of aquaculture in this context. The method involved is inspired from a « mesology », meaning that it focuses primarily on the human beings’ relation to nature. We argue that the development of aquaculture in Canada could be a beneficial strategy because it creates new places of contact between men and nature through a relation of domestication. Nevertheless, the introduction of high-tech methods such as transgenic manipulations can reduce the quality and the diversity of these relations because they are essentially modern techniques