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7 results on '"European Project: 201370,EC:FP7:HEALTH,FP7-HEALTH-2007-A,LUPA(2008)"'

1. PNPLA1 mutations cause autosomal recessive congenital ichthyosis in golden retriever dogs and humans

Author

Anais Grall, Céline Derbois, Matthieu Le Gallo, Ingrid Hausser, Laetitia Lagoutte, Sébastien Küry, Judith Fischer, Catherine André, Emmanuelle Bourrat, Emmanuel Bensignor, Sandrine Planchais, Franz P.W. Radner, Éric Guaguère, Francis Galibert, Rudolf Zechner, Susanne Grond, Jacques Fontaine, Robert Zimmermann, Gwang-Jin Kim, Mark Lathrop, Frédérique Degorce-Rubiales, Anne Thomas, Didier Pin, Christophe Hitte, Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Clinique Vétérinaire Saint Bernard, Institute of Molecular Biosciences, Karl-Franzens-Universität Graz, Service de dermatologie [Paris], Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Department of dermatology, University clinic Heidelberg, Electron Microscopy Core Facility, Universität Heidelberg [Heidelberg], Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut de Génomique d'Evry (IG), Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Institute for Human Genetics, University Clinic Freiburg, Faculty for Biology, University of Freiburg [Freiburg], Laboratoire d'Anatomie Pathologique Vétérinaire du Sud-Ouest, Animal Genetics Laboratory, Antagene, Service d'ORL et de Chirurgie Cervicofaciale, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Clinique Vétérinaire de la Boulais, Clinique vétérinaire, Clinique vétérinaire, Bruxelles, Interactions Cellules Environnement - UR (ICE), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Centre d'Etude du Polymorphisme Humain (CEPH), Université Paris Diderot - Paris 7 (UPD7)-Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Fondation Jean Dausset, Zentrum für Biosystemanalyse, Albert-Ludwigs-Universität Freiburg, This study was supported by CNRS, the European Commission (FP7-LUPA, GA-201370). R. Zechner and R. Zimmermann were supported by the FWF F30 SFB Lipotox, Z136 Wittgenstein, the GEN-AU project GOLD by the Austrian Ministry of Science and Research and FFG. I.H. was supported by the NIRK Network (German BMBF 01GM0904)., European Project: 201370,EC:FP7:HEALTH,FP7-HEALTH-2007-A,LUPA(2008), Institut de Génétique et Développement de Rennes ( IGDR ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Centre National de la Recherche Scientifique ( CNRS ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Assistance publique - Hôpitaux de Paris (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris]-Université Paris Diderot - Paris 7 ( UPD7 ), Centre National de Génotypage ( CNG ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), Institut de Génomique d'Evry ( IG ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -CHU Trousseau [APHP], Unité de Dermatologie, VetAgro Sup ( VAS ), Centre d'Etude du Polymorphisme Humain ( CEPH ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut Universitaire d'Hématologie ( IUH ), Université Paris Diderot - Paris 7 ( UPD7 ) -Fondation Jean Dausset, European Project : 201370,EC:FP7:HEALTH,FP7-HEALTH-2007-A,LUPA ( 2008 ), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Universität Heidelberg [Heidelberg] = Heidelberg University, Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), De Villemeur, Hervé, and Unravelling the molecular basis of common complex human disorders using the dog as a model system - LUPA - - EC:FP7:HEALTH2008-01-01 - 2012-06-30 - 201370 - VALID

Subjects
Male, MESH : Molecular Sequence Data, [SDV.GEN] Life Sciences [q-bio]/Genetics, MESH: Base Sequence, medicine.disease_cause, 0403 veterinary science, MESH: Dogs, MESH: INDEL Mutation, MESH: Lipase, MESH : Dogs, INDEL Mutation, Congenital ichthyosis, Missense mutation, MESH : Female, MESH: Animals, MESH: Codon, Nonsense, Cells, Cultured, Skin, Genetics, 0303 health sciences, Mutation, 04 agricultural and veterinary sciences, Lamellar ichthyosis, MESH : Adult, MESH : Lipase, MESH : Dermatologic Agents, MESH : Codon, Nonsense, MESH: Ichthyosis, Lamellar, Codon, Nonsense, Female, MESH : Genome-Wide Association Study, MESH: Cells, Cultured, Adult, 040301 veterinary sciences, MESH : Male, Nonsense mutation, Molecular Sequence Data, Mutation, Missense, ALOX12B, Golden Retriever, Genes, Recessive, MESH: Nitrendipine, Biology, 03 medical and health sciences, Dogs, MESH: Skin, MESH : Cells, Cultured, medicine, MESH : Skin, Animals, Humans, Indel, MESH : INDEL Mutation, MESH: Genes, Recessive, 030304 developmental biology, MESH: Mutation, Missense, [SDV.GEN]Life Sciences [q-bio]/Genetics, MESH: Humans, MESH: Molecular Sequence Data, Base Sequence, Nitrendipine, MESH : Humans, MESH : Ichthyosis, Lamellar, MESH : Genes, Recessive, MESH: Adult, Lipase, [SDV.MHEP.DERM] Life Sciences [q-bio]/Human health and pathology/Dermatology, medicine.disease, MESH : Nitrendipine, MESH: Male, MESH: Dermatologic Agents, MESH: Genome-Wide Association Study, MESH : Base Sequence, MESH : Animals, Dermatologic Agents, [ SDV.GEN ] Life Sciences [q-bio]/Genetics, [ SDV.MHEP.DERM ] Life Sciences [q-bio]/Human health and pathology/Dermatology, MESH: Female, MESH : Mutation, Missense, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology, Ichthyosis, Lamellar, Genome-Wide Association Study
Abstract

International audience; Ichthyoses comprise a heterogeneous group of genodermatoses characterized by abnormal desquamation over the whole body, for which the genetic causes of several human forms remain unknown. We used a spontaneous dog model in the golden retriever breed, which is affected by a lamellar ichthyosis resembling human autosomal recessive congenital ichthyoses (ARCI), to carry out a genome-wide association study. We identified a homozygous insertion-deletion (indel) mutation in PNPLA1 that leads to a premature stop codon in all affected golden retriever dogs. We subsequently found one missense and one nonsense mutation in the catalytic domain of human PNPLA1 in six individuals with ARCI from two families. Further experiments highlighted the importance of PNPLA1 in the formation of the epidermal lipid barrier. This study identifies a new gene involved in human ichthyoses and provides insights into the localization and function of this yet uncharacterized member of the PNPLA protein family.

Published
2011
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2. Genome wide association study of 40 clinical measurements in eight dog breeds

Author

Hannes Lohi, Eija H. Seppälä, Merete Fredholm, Jørgen Koch, Helle Friis Proschowsky, Yukihide Momozawa, Laurent Tiret, Vassiliki Gouni, Valérie Chetboul, Anne-Sophie Lequarré, Anne-Christine Merveille, Michel Georges, J.L. Willesen, Maria Wiberg, Géraldine Battaille, Université de Liège, RIKEN Center for Integrative Medical Sciences [Yokohama] (RIKEN IMS), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, University of Copenhagen = Københavns Universitet (UCPH), The Danish Kennel Club [Danemark] (DKC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Unité de Cardiologie d'Alfort [Maisons-Alfort] (UCA), École nationale vétérinaire - Alfort (ENVA)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Biologie du système neuromusculaire - Biology of the neuromuscular system [Maisons-Alfort] (BNMS - Team 10), École nationale vétérinaire - Alfort (ENVA)-Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), This work was funded by Grant from the European Commission (FP7-LUPA, GA-201370) to M.G., Mochida Memorial Foundation for Medical and Pharmaceutical Research to Y.M., and Jane and Aatos Erkko Foundation, The Academy of Finland and the Sigrid Juselius Foundation to H.L. Y.M. benefitted from fellowship from Grant-in-Aid for JSPS Fellows and Postdoctoral Fellowship for Research Abroad from JSPS., European Project: 201370,EC:FP7:HEALTH,FP7-HEALTH-2007-A,LUPA(2008), University of Helsinki, University of Copenhagen = Københavns Universitet (KU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, École nationale vétérinaire d'Alfort (ENVA)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), École nationale vétérinaire d'Alfort (ENVA)-Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Equine and Small Animal Medicine, Maria Wiberg / Principal Investigator, University Management, Department of Medical and Clinical Genetics, Veterinary Biosciences, Helsinki One Health (HOH), Hannes Tapani Lohi / Principal Investigator, Veterinary Genetics, Biosciences, Bodescot, Myriam, and Unravelling the molecular basis of common complex human disorders using the dog as a model system - LUPA - - EC:FP7:HEALTH2008-01-01 - 2012-06-30 - 201370 - VALID

Subjects
Male, Quantitative trait loci, GOLDEN RETRIEVER DOGS, LOCI, lcsh:Medicine, Genome-wide association study, Locus (genetics), [SDV.GEN.GA] Life Sciences [q-bio]/Genetics/Animal genetics, Disease, Breeding, Biology, 413 Veterinary science, Polymorphism, Single Nucleotide, Genome-wide association studies, DISEASE, Chromosomes, Article, 03 medical and health sciences, chemistry.chemical_compound, Dogs, 0302 clinical medicine, Animals, Humans, SNP, Genetic Predisposition to Disease, Dog Diseases, lcsh:Science, Animal breeding, 030304 developmental biology, Chromosome 13, Genetics, ARCHITECTURE, 0303 health sciences, COMPLEX, Multidisciplinary, lcsh:R, 1184 Genetics, developmental biology, physiology, Alanine Transaminase, [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics, SIZE, Phenotype, Fructosamine, chemistry, Cohort, Physical exam, lcsh:Q, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

The domestic dog represents an ideal model for identifying susceptibility genes, many of which are shared with humans. In this study, we investigated the genetic contribution to individual differences in 40 clinically important measurements by a genome-wide association study (GWAS) in a multinational cohort of 472 healthy dogs from eight breeds. Meta-analysis using the binary effects model after breed-specific GWAS, identified 13 genome-wide significant associations, three of them showed experimental-wide significant associations. We detected a signal at chromosome 13 for the serum concentration of alanine aminotransferase (ALT) in which we detected four breed-specific signals. A large proportion of the variance of ALT (18.1–47.7%) was explained by this locus. Similarly, a single SNP was also responsible for a large proportion of the variance (6.8–78.4%) for other measurements such as fructosamine, stress during physical exam, glucose, and morphometric measurements. The genetic contribution of single variant was much larger than in humans. These findings illustrate the importance of performing meta-analysis after breed-specific GWAS to reveal the genetic contribution to individual differences in clinically important measurements, which would lead to improvement of veterinary medicine.

Published
2020
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3. FEELnc: a tool for long non-coding RNA annotation and its application to the dog transcriptome

Author

Wucher, Valentin, Legeai, Fabrice, Hédan, Benoît, Rizk, Guillaume, Lagoutte, Lætitia, Leeb, Tosso, Jagannathan, Vidhya, Cadieu, Edouard, David, Audrey, Lohi, Hannes, Cirera, Susanna, Fredholm, Merete, Botherel, Nadine, Leegwater, Peter A J, Le Béguec, Céline, Fieten, Hille, Johnson, Jeremy, Alföldi, Jessica, André, Catherine, Lindblad-Toh, Kerstin, Hitte, Christophe, Derrien, Thomas, Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Scalable, Optimized and Parallel Algorithms for Genomics (GenScale), Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-GESTION DES DONNÉES ET DE LA CONNAISSANCE (IRISA-D7), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Institut de Génétique, Environnement et Protection des Plantes (IGEPP), Institut National de la Recherche Agronomique (INRA)-Université de Rennes (UR)-AGROCAMPUS OUEST, Institute of Genetics, University of Bern, Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Folkhälsan Institute of Genetics, Department of Veterinary Clinical and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), IT University of Copenhagen (ITU), Universiteit Utrecht, Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Science for Life Laboratory, Uppsala University-Department of Medical Biochemistry and Microbiology, 7th PCRD 'Health programs' LUPA consortium [FP7] [GA: 201370], French National Research Agency [ANR-11-INBS-0003], European Young Investigator Award from European Science Foundation, European Research Council, ANR-11-INBS-0003,CRB-Anim,Réseau de Centres de Ressources Biologiques pour les animaux domestiques(2011), European Project: 201370,EC:FP7:HEALTH,FP7-HEALTH-2007-A,LUPA(2008), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Bretagne Sud (UBS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National de Recherche en Informatique et en Automatique (Inria)-École normale supérieure - Rennes (ENS Rennes)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-CentraleSupélec-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Bretagne Sud (UBS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-École normale supérieure - Rennes (ENS Rennes)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Institut National de la Recherche Agronomique (INRA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-AGROCAMPUS OUEST, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), University of Helsinki, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), IT University of Copenhagen, Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes 1 (UR1), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), ANR-11-INBS-0003/11-INBS-0003,CRB-Anim,Réseau de Centres de Ressources Biologiques pour les animaux domestiques(2011), Research Programs Unit, Hannes Tapani Lohi / Principal Investigator, Veterinary Biosciences, Veterinary Genetics, and Research Programme for Molecular Neurology

Subjects
COMPARATIVE GENOMICS, PREDICTION, Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy), 610 Medicine & health, arn non codant, Mice, Open Reading Frames, Dogs, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Animals, Humans, RECONSTRUCTION, RNA, Messenger, analyse du transcriptome, Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci), Genome, IDENTIFICATION, Sequence Analysis, RNA, HUMAN-CELLS, génome, Decision Trees, Molecular Sequence Annotation, QUANTIFICATION, GENE, CANCER, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], EVOLUTION, Benchmarking, [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics, DIFFERENTIATION, Gene Expression Regulation, 1182 Biochemistry, cell and molecular biology, Methods Online, 570 Life sciences, biology, 590 Animals (Zoology), RNA, Long Noncoding, Transcriptome, Software
Abstract

International audience; Whole transcriptome sequencing (RNA-seq) has become a standard for cataloguing and monitoring RNA populations. One of the main bottlenecks, however, is to correctly identify the different classes of RNAs among the plethora of reconstructed transcripts, particularly those that will be translated (mRNAs) from the class of long non-coding RNAs (lncRNAs). Here, we present FEELnc (FlExible Extraction of LncRNAs), an alignment-free program that accurately annotates lncRNAs based on a Random Forest model trained with general features such as multi k-mer frequencies and relaxed open reading frames. Benchmarking versus five state-of-the-art tools shows that FEELnc achieves similar or better classification performance on GENCODE and NONCODE data sets. The program also provides specific modules that enable the user to fine-tune classification accuracy, to formalize the annotation of lncRNA classes and to identify lncRNAs even in the absence of a training set of non-coding RNAs. We used FEELnc on a real data set comprising 20 canine RNA-seq samples produced by the European LUPA consortium to substantially expand the canine genome annotation to include 10 374 novel lncRNAs and 58 640 mRNA transcripts. FEELnc moves beyond conventional coding potential classifiers by providing a standardized and complete solution for annotating lncRNAs and is freely available at https://github.com/tderrien/FEELnc.

Published
2017
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4. Novel origins of copy number variation in the dog genome

Author

Christophe Hitte, Michael C. Zody, Michele Perloski, Jonas Berglund, Matthew T. Webster, Hannes Lohi, Ted Sharpe, Elisa M. Nevalainen, Anna-Maja Molin, Catherine André, Kerstin Lindblad-Toh, Science for Life Laboratory, Uppsala University-Department of Medical Biochemistry and Microbiology, Department of Basic Veterinary Biosciences, HMNC Brain Health-Biomedicum Helsinki-Folkhälsan Institute of Genetics, Department of Animal Bredding and Genetics, Swedish University of Agricultural Sciences (SLU), Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Institut de Génétique et Développement de Rennes (IGDR), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), The LUPA consortium (lupa) (marilou.ramospamplona@ULG.AC.BE), European Project: 201370,EC:FP7:HEALTH,FP7-HEALTH-2007-A,LUPA(2008), De Villemeur, Hervé, Unravelling the molecular basis of common complex human disorders using the dog as a model system - LUPA - - EC:FP7:HEALTH2008-01-01 - 2012-06-30 - 201370 - VALID, and Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )

Subjects
Male, 0106 biological sciences, Genome instability, DNA Copy Number Variations, Genotype, Breeding, Biology, 01 natural sciences, Genome, Genomic Instability, Structural variation, 03 medical and health sciences, Dogs, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Naturvetenskap, Animals, Copy-number variation, Gene, PRDM9, 030304 developmental biology, Genetics, Comparative Genomic Hybridization, 0303 health sciences, Research, Reproducibility of Results, Phenotype, Genetic Loci, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Female, Natural Sciences, GC-content, 010606 plant biology & botany, Comparative genomic hybridization
Abstract

BACKGROUND: Copy number variants (CNVs) account for substantial variation between genomes and are a major source of normal and pathogenic phenotypic differences. The dog is an ideal model to investigate mutational mechanisms that generate CNVs as its genome lacks a functional ortholog of the PRDM9 gene implicated in recombination and CNV formation in humans. Here we comprehensively assay CNVs using high-density array comparative genomic hybridization in 50 dogs from 17 dog breeds and 3 gray wolves. RESULTS: We use a stringent new method to identify a total of 430 high-confidence CNV loci, which range in size from 9 kb to 1.6 Mb and span 26.4 Mb, or 1.08%, of the assayed dog genome, overlapping 413 annotated genes. Of CNVs observed in each breed, 98% are also observed in multiple breeds. CNVs predicted to disrupt gene function are significantly less common than expected by chance. We identify a significant overrepresentation of peaks of GC content, previously shown to be enriched in dog recombination hotspots, in the vicinity of CNV breakpoints. CONCLUSIONS: A number of the CNVs identified by this study are candidates for generating breed-specific phenotypes. Purifying selection seems to be a major factor shaping structural variation in the dog genome, suggesting that many CNVs are deleterious. Localized peaks of GC content appear to be novel sites of CNV formation in the dog genome by non-allelic homologous recombination, potentially activated by the loss of PRDM9. These sequence features may have driven genome instability and chromosomal rearrangements throughout canid evolution. Additional author: The LUPA Consortium (www.eurolupa.org)

Published
2012
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5. LUPA: a European initiative taking advantage of the canine genome architecture for unravelling complex disorders in both human and dogs

Author

Michel Georges, Christophe Hitte, Anne-Sophie Lequarré, Merete Fredholm, Tosso Leeb, Catherine André, Hannes Lohi, Leif Andersson, Kerstin Lindblad-Toh, Groupe Interdisciplinaire de Génoprotéomique Appliquée (GIGA-Research), Université de Liège, Science for Life Laboratory, Uppsala University-Department of Medical Biochemistry and Microbiology, Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Faculty of Life Sciences, Division of Genetics and Bioinformatics, Faculty of Life Science [Copenhagen], University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), Institute of Genetics, Vetsuisse Faculty-University of Bern, Folkhälsan Institute of Genetics, HMNC Brain Health-Department of Veterinary Biosciences-Program in Molecular Medicine-Biomedicum Helsinki, Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], European Project: 201370,EC:FP7:HEALTH,FP7-HEALTH-2007-A,LUPA(2008), Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), De Villemeur, Hervé, Unravelling the molecular basis of common complex human disorders using the dog as a model system - LUPA - - EC:FP7:HEALTH2008-01-01 - 2012-06-30 - 201370 - VALID, Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)

Subjects
International Cooperation, ved/biology.organism_classification_rank.species, [SDV.GEN] Life Sciences [q-bio]/Genetics, Disease, Canine, 0403 veterinary science, MESH: Dogs, Human health, Single nucleotide polymorphism arrays, MESH: Animals, Dog Diseases, Genetics, 0303 health sciences, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, MESH: Polymorphism, Single Nucleotide, MESH: DNA, Chromosome Mapping, 04 agricultural and veterinary sciences, Pedigree, Europe, LUPA, Canine genome, 040301 veterinary sciences, MESH: Pedigree, MESH: Dog Diseases, High density, Single-nucleotide polymorphism, Computational biology, Biology, Polymorphism, Single Nucleotide, 03 medical and health sciences, Dogs, Animals, Humans, SNP, Inherited disorders, Model organism, 030304 developmental biology, Genetic association, [SDV.GEN]Life Sciences [q-bio]/Genetics, MESH: Humans, General Veterinary, ved/biology, DNA, Disease Models, Animal, MESH: International Cooperation, MESH: Genome-Wide Association Study, Animal Science and Zoology, MESH: Europe, MESH: Disease Models, Animal, MESH: Chromosome Mapping, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Genome-Wide Association Study
Abstract

International audience; The domestic dog offers a unique opportunity to explore the genetic basis of disease, morphology and behaviour. Humans share many diseases with our canine companions, making dogs an ideal model organism for comparative disease genetics. Using newly developed resources, genome-wide association studies in dog breeds are proving to be exceptionally powerful. Towards this aim, veterinarians and geneticists from 12 European countries are collaborating to collect and analyse the DNA from large cohorts of dogs suffering from a range of carefully defined diseases of relevance to human health. This project, named LUPA, has already delivered considerable results. The consortium has collaborated to develop a new high density single nucleotide polymorphism (SNP) array. Mutations for four monogenic diseases have been identified and the information has been utilised to find mutations in human patients. Several complex diseases have been mapped and fine mapping is underway. These findings should ultimately lead to a better understanding of the molecular mechanisms underlying complex diseases in both humans and their best friend.

Published
2011
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6. Comparison of buccal and blood-derived canine DNA, either native or whole genome amplified, for array-based genome-wide association studies

Author

Kerstin Lindblad-Toh, Mark Hansen, Anne Thomas, Laetitia Lagoutte, Juan F. Medrano, Janelle M. Belanger, Anita M. Oberbauer, Katarina Tengvall, Gonzalo Rincon, Catherine André, Cindy Lawley, Department of Animal Science, University of California [Davis] (UC Davis), University of California-University of California, Science for Life Laboratory, Uppsala University-Department of Medical Biochemistry and Microbiology, Institut de Génétique et Développement de Rennes (IGDR), Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Animal Genetics Laboratory, Antagene, Illumina, Inc., Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], The study was partly supported by the European Commission (FP7-LUPA, GA-201370), the AKC Canine Health Foundation (#0225, 1236-A/B), and the Agricultural Experiment Station of California., European Project: 201370,EC:FP7:HEALTH,FP7-HEALTH-2007-A,LUPA(2008), University of California (UC)-University of California (UC), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), De Villemeur, Hervé, and Unravelling the molecular basis of common complex human disorders using the dog as a model system - LUPA - - EC:FP7:HEALTH2008-01-01 - 2012-06-30 - 201370 - VALID

Subjects
040301 veterinary sciences, Short Report, lcsh:Medicine, Single-nucleotide polymorphism, Genome-wide association study, [SDV.GEN] Life Sciences [q-bio]/Genetics, Biology, Genome, General Biochemistry, Genetics and Molecular Biology, 0403 veterinary science, Structural variation, 03 medical and health sciences, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Copy-number variation, lcsh:Science (General), Genotyping, lcsh:QH301-705.5, 030304 developmental biology, Genetics, Whole Genome Amplification, Medicine(all), 0303 health sciences, [SDV.GEN]Life Sciences [q-bio]/Genetics, Biochemistry, Genetics and Molecular Biology(all), lcsh:R, 04 agricultural and veterinary sciences, General Medicine, lcsh:Biology (General), [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], SNP array, lcsh:Q1-390
Abstract

Background The availability of array-based genotyping platforms for single nucleotide polymorphisms (SNPs) for the canine genome has expanded the opportunities to undertake genome-wide association (GWA) studies to identify the genetic basis for Mendelian and complex traits. Whole blood as the source of high quality DNA is undisputed but often proves impractical for collection of the large numbers of samples necessary to discover the loci underlying complex traits. Further, many countries prohibit the collection of blood from dogs unless medically necessary thereby restricting access to critical control samples from healthy dogs. Alternate sources of DNA, typically from buccal cytobrush extractions, while convenient, have been suggested to have low yield and perform poorly in GWA. Yet buccal cytobrushes provide a cost-effective means of collecting DNA, are readily accepted by dog owners, and represent a large resource base in many canine genetics laboratories. To increase the DNA quantities, whole genome amplification (WGA) can be performed. Thus, the present study assessed the utility of buccal-derived DNA as well as whole genome amplification in comparison to blood samples for use on the most recent iteration of the canine HD SNP array (Illumina). Findings In both buccal and blood samples, whether whole genome amplified or not, 97% of the samples had SNP call rates in excess of 80% indicating that the vast majority of the SNPs would be suitable to perform association studies regardless of the DNA source. Similarly, there were no significant differences in marker intensity measurements between buccal and blood samples for copy number variations (CNV) analysis. Conclusions All DNA samples assayed, buccal or blood, native or whole genome amplified, are appropriate for use in array-based genome-wide association studies. The concordance between subsets of dogs for which both buccal and blood samples, or those samples whole genome amplified, was shown to average >99%. Thus, the two DNA sources were comparable in the generation of SNP genotypes and intensity values to estimate structural variation indicating the utility for the use of buccal cytobrush samples and the reliability of whole genome amplification for genome-wide association and CNV studies.

Published
2011
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7. Identification of Genomic Regions Associated with Phenotypic Variation between Dog Breeds using Selection Mapping

Author

Vaysse, A., Ratnakumar, A., Derrien, T., Axelsson, E., Rosengren Pielberg, G., Sigurdsson, S., Fall, T., Seppälä, E.H., Hansen, M.S., Lawley, C.T., Karlsson, E.K., Bannasch, D.L., Vilà, C., Lohi, H., Galibert, F., Fredholm, M., Häggström, O., Hedhammar, A., André, C., Lindblad-Toh, K., Hitte, C., van Steenbeek, F.G., Fieten, H., Leegwater, P.A.J., LUPA Consortium, x, Webster, M.T., Advances in Veterinary Medicine, Tissue Repair, Geneeskunde van gezelschapsdieren, Research Programs Unit, Department of Medical and Clinical Genetics, Research Programme of Molecular Medicine, Veterinary Biosciences, Departments of Faculty of Veterinary Medicine, Broad Institute of MIT and Harvard, Sigurdsson, Snaever, Sigurdsson, Snaevar, Karlsson, Elinor K., Lindblad-Toh, Kerstin, Webster, Matthew T., Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS), Science for Life Laboratory, Uppsala University-Department of Medical Biochemistry and Microbiology, Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], Department of Basic Veterinary Biosciences, HMNC Brain Health-Biomedicum Helsinki-Folkhälsan Institute of Genetics, Illumina, Inc., FAS Center for Systems Biology, Harvard University [Cambridge], Department of Population Health and Reproduction, University of California [Davis] (UC Davis), University of California-University of California, Department of Integrative Ecology (CSIC), Estación Biológica de Doñana (EBD), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC)-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Faculty of Life Sciences, Division of Genetics and Bioinformatics, Faculty of Life Science [Copenhagen], University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), Swedish University of Agricultural Sciences (SLU), This research was mainly supported by The LUPA Consortium, which is a Collaborative Research Project funded by the European Commission under the 7th Research Framework Programme (www.eurolupa.org)., The LUPA Consortium, European Project: 201370,EC:FP7:HEALTH,FP7-HEALTH-2007-A,LUPA(2008), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Harvard University, University of California (UC)-University of California (UC), University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), De Villemeur, Hervé, and Unravelling the molecular basis of common complex human disorders using the dog as a model system - LUPA - - EC:FP7:HEALTH2008-01-01 - 2012-06-30 - 201370 - VALID

Subjects
POSITIVE SELECTION, Genotyping Techniques, Genome-wide association study, Breeding, 413 Veterinary science, MESH: Dogs, 0302 clinical medicine, MESH: Behavior, Animal, MESH: Animals, Genome Sequencing, MESH: Genetic Variation, mapping, MESH: Phylogeny, Genome Evolution, Phylogeny, 0303 health sciences, education.field_of_study, Behavior, Animal, MESH: Polymorphism, Single Nucleotide, 1184 Genetics, developmental biology, physiology, Genomics, Genome Scans, selection, dog, identification, genomic, Fixation (population genetics), COAT COLOR, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], PERSONALITY-TRAITS, Gene Flow, Genetics and Breeding, education, Single-nucleotide polymorphism, MESH: Breeding, MESH: Phenotype, 03 medical and health sciences, CANIS-FAMILIARIS, Effective Population Size, MESH: Genotyping Techniques, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Genome-Wide Association Studies, Genetics, Genetik, Biology, Molecular Biology, Ecology, Evolution, Behavior and Systematics, [SDV.GEN]Life Sciences [q-bio]/Genetics, Genetic Drift, MESH: Ear, Computational Biology, Genetic Variation, MESH: Haplotypes, Phenotypic trait, HAPLOTYPE STRUCTURE, variation phénotypique, Mutation, MESH: Genome-Wide Association Study, marqueur de sélection, Population Genetics, 030217 neurology & neurosurgery, Evolutionary Genetics, Cancer Research, cartographie génomique, LINKAGE DISEQUILIBRIUM, MESH: Selection, Genetic, [SDV.GEN] Life Sciences [q-bio]/Genetics, Natural Selection, Body Size, WIDE ASSOCIATION, Genetics (clinical), DOMESTIC DOG, MESH: Heterozygote, Gene Ontologies, Homozygote, race canine, 402 Animal and Dairy Science, Ear, Gene Pool, Phenotype, Research Article, MESH: Homozygote, Heterozygote, 403 Veterinary Science, lcsh:QH426-470, Population, Polymorphism, Single Nucleotide, Dogs, Genetic drift, Genome Analysis Tools, DNA-SEQUENCE, Evolutionary Modeling, Genetic variation, Animals, Selection, Genetic, Selection (genetic algorithm), 030304 developmental biology, Evolutionary Biology, MESH: Body Size, Genetic Maps, Comparative Genomics, GENE, lcsh:Genetics, Haplotypes, Neutral Theory, Genetic Polymorphism, Animal Genetics, Genome-Wide Association Study
Abstract

The extraordinary phenotypic diversity of dog breeds has been sculpted by a unique population history accompanied by selection for novel and desirable traits. Here we perform a comprehensive analysis using multiple test statistics to identify regions under selection in 509 dogs from 46 diverse breeds using a newly developed high-density genotyping array consisting of .170,000 evenly spaced SNPs. We first identify 44 genomic regions exhibiting extreme differentiation across multiple breeds. Genetic variation in these regions correlates with variation in several phenotypic traits that vary between breeds, and we identify novel associations with both morphological and behavioral traits. We next scan the genome for signatures of selective sweeps in single breeds, characterized by long regions of reduced heterozygosity and fixation of extended haplotypes. These scans identify hundreds of regions, including 22 blocks of homozygosity longer than one megabase in certain breeds. Candidate selection loci are strongly enriched for developmental genes. We chose one highly differentiated region, associated with body size and ear morphology, and characterized it using high-throughput sequencing to provide a list of variants that may directly affect these traits. This study provides a catalogue of genomic regions showing extreme reduction in genetic variation or population differentiation in dogs, including many linked to phenotypic variation. The many blocks of reduced haplotype diversity observed across the genome in dog breeds are the result of both selection and genetic drift, but extended blocks of homozygosity on a megabase scale appear to be best explained by selection. Further elucidation of the variants under selection will help to uncover the genetic basis of complex traits and disease.

Published
2011
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