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102. ADAM23 is a common risk gene for canine idiopathic epilepsy

Author

Koskinen, Lotta L. E., primary, Seppälä, Eija H., additional, Weissl, Jutta, additional, Jokinen, Tarja S., additional, Viitmaa, Ranno, additional, Hänninen, Reetta L., additional, Quignon, Pascale, additional, Fischer, Andrea, additional, André, Catherine, additional, and Lohi, Hannes, additional

Published
2017
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103. A Point Mutation in a lincRNA Upstream of GDNF Is Associated to a Canine Insensitivity to Pain: A Spontaneous Model for Human Sensory Neuropathies

Author

Plassais, Jocelyn, primary, Lagoutte, Laetitia, additional, Correard, Solenne, additional, Paradis, Manon, additional, Guaguère, Eric, additional, Hédan, Benoit, additional, Pommier, Alix, additional, Botherel, Nadine, additional, Cadiergues, Marie-Christine, additional, Pilorge, Philippe, additional, Silversides, David, additional, Bizot, Maud, additional, Samuels, Mark, additional, Arnan, Carme, additional, Johnson, Rory, additional, Hitte, Christophe, additional, Salbert, Gilles, additional, Méreau, Agnès, additional, Quignon, Pascale, additional, Derrien, Thomas, additional, and André, Catherine, additional

Published
2016
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104. In vitro and in vivo characterization of immunomodulatory properties of MuStem cells

Author

Lorant, Judith, Jaulin, Nicolas, Larcher, Thibaut, Hédan, Benoît, Deschamps, Jack-Yves, Leroux, Isabelle, Zuber, Céline, Schleder, Cindy, Ledevin, Mireille, Dutilleul, Maeva, Goubin, Hélicia, Jounier, Corinne, André, Catherine, Cherel, Yan, Adjali, Oumeya, Rouger, Karl, Physiopathologie Animale et bioThérapie du muscle et du système nerveux (PAnTher), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), LUNAM Université [Nantes Angers Le Mans], Atlantic Gene Therapies, UMR1089, Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Boisbonne Gene and Cell Therapy Center, Partenaires INRAE, ESGCT., Institut National de la Recherche Agronomique (INRA)-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), 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
[SDV.IMM]Life Sciences [q-bio]/Immunology, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience

Published
2014

106. Dépistage génétique

Author

Abitbol, Marie, André, Catherine, Thomas, Anne, and Abitbol, Marie

Subjects
[SDV] Life Sciences [q-bio], [SDV.BA] Life Sciences [q-bio]/Animal biology, [SDV.BA.MVSA] Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, ComputingMilieux_MISCELLANEOUS
Published
2013

107. The MTAP-CDKN2A Locus Confers Susceptibility to a Naturally Occurring Canine Cancer

Author

Shearin, Abigail, Hédan, Benoît, Cadieu, Edouard, Erich, Suzanne, Schmidt, Emmett, Faden, Daniel, Cullen, John, Abadie, Jérôme, Kwon, Erika, Gröne, Andrea, Devauchelle, Patrick, Rimbault, Maud, Karyadi, Danielle, Lynch, Mary, Galibert, Francis, Breen, Matthew, Rutteman, Gerard, André, Catherine, Parker, Heidi, Ostrander, Elaine, De Villemeur, Hervé, Cancer Genetics Branch, National Institute of Health (NIH)-National Human Genome Research Institute (NHGRI), Howard Hughes Medical Institute [Chevy Chase] (HHMI), Howard Hughes Medical Institute (HHMI), Department of Molecular Biomedical Sciences, North Carolina State University [Raleigh] (NC State), University of North Carolina System (UNC)-University of North Carolina System (UNC)-College of Veterinary Medicine Raleigh, Department of Population Health and Pathobiology, 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 ), Faculty of Veterinary Medicine, Utrecht University [Utrecht], Cancer Research Center, Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], Immuno-Endocrinologie Cellulaire et Moléculaire (IECM), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire de Nantes-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Centre anti-cancereux, École nationale vétérinaire - Alfort (ENVA), Lineberger Comprehensive Cancer Center (UNC Lineberger), University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC)-University of North Carolina System (UNC), Intramural Program of the National Human Genome Research Institute at NIH, AKC-Canine Health Foundation (grant 2667, 935), CNRS and French Association for Swiss dogs, NIH NCI (R01 CA69069, NIH U01 AI07033), Harvard Breast Cancer SPORE (P50 CA89393), Alberto Vittoni Award, Committee of Preventive Health Care of the Netherlands Royal Society of Veterinary Medicine, breed societies for Bernese mountain dogs in the Netherlands, breed societies for Bernese mountain dogs in the Germany, breed societies for Bernese mountain dogs in the Austria, and breed societies for Bernese mountain dogs in the Belgium

Subjects
Dogs, Histiocytic sarcoma, [SDV.CAN] Life Sciences [q-bio]/Cancer, p16, [SDV.CAN]Life Sciences [q-bio]/Cancer, Genome Wide Association Study, Cancer
Abstract

International audience; BACKGROUND: Advantages offered by canine population substructure, combined with clinical similarity to human disease makes the dog a particularly attractive system for finding genes associated with cancer. Cancers that have been difficult to study in human families or populations are of particular interest, especially those associated with one or a small number of breeds and a high level of occurrence. Histiocytic sarcoma (HS) is a rare and poorly understood neoplasm in humans, however it occurs in 15-25% of Bernese Mountain Dogs (BMD). METHODS: Genomic DNA was collected from affected and unaffected BMD in both North America and Europe. Both independent and combined genome wide association studies (GWAS) from the two geographic populations were used to identify cancer associated loci. Fine mapping and sequencing was used to narrow the primary locus.RESULTS: GWAS revealed a cancer-associated locus shared by both populations. The locus contains a single haplotype spanning MTAP and part of CDKN2A that is present in 96% of all affected BMD. The haplotype is within the region homologous to human chromosome 9p21, which has been implicated in numerous complex genetic diseases including several cancers. CONCLUSIONS: We present the first GWAS for HS in any species. The data identify an associated haplotype in the highly cited tumor suppressor locus near CDKN2A. These data demonstrate the power of studying distinctive malignancies in highly predisposed dog breeds. Impact: Here, we establish a naturally-occurring model of cancer susceptibility due to CDKN2 dysregulation, thus providing insight regarding this cancer-associated, complex, and poorly understood genomic region.

Published
2012

108. Participation des habitants. Quel genre de ville durable?

Author

Hofmann, Elisabeth, André, Catherine, Palueau, Marie-Françoise, Les Afriques dans le monde (LAM), and Université Montesquieu - Bordeaux 4-Institut d'Études Politiques [IEP] - Bordeaux-Centre National de la Recherche Scientifique (CNRS)

Subjects
Participation des femmes, Femmes, [SHS.SCIPO] Humanities and Social Sciences/Political science, [SHS.SCIPO]Humanities and Social Sciences/Political science, ComputingMilieux_MISCELLANEOUS, Politique urbaine
Abstract

National audience

Published
2011

109. [Frequency of gene defects in selected European retriever populations]

Author

Owczarek-Lipska, M., Thomas, A., André, Catherine, Hölzer, S., Leeb, 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), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)

Subjects
[SDV.GEN]Life Sciences [q-bio]/Genetics, Inborn, Dogs, Genetic Diseases, Genetic Diseases, Inborn, Animals, Dog Diseases, Breeding, ComputingMilieux_MISCELLANEOUS, Switzerland
Abstract

International audience; no abstract

Published
2011

111. A Spontaneous KRT16 Mutation in a Dog Breed: A Model for Human Focal Non-Epidermolytic Palmoplantar Keratoderma (FNEPPK)

Author

Plassais, Jocelyn, primary, Guaguère, Eric, additional, Lagoutte, Laetitia, additional, Guillory, Anne-Sophie, additional, de Citres, Caroline Dufaure, additional, Degorce-Rubiales, Frédérique, additional, Delverdier, Maxence, additional, Vaysse, Amaury, additional, Quignon, Pascale, additional, Bleuart, Céline, additional, Hitte, Christophe, additional, Fautrel, Alain, additional, Kaerle, Cecile, additional, Bellaud, Pascale, additional, Bensignor, Emmanuel, additional, Queney, Guillaume, additional, Bourrat, Emmanuelle, additional, Thomas, Anne, additional, and André, Catherine, additional

Published
2015
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112. Screening for a canine model of choroideremia exclusively identifies nonpathogenic CHM variants

Author

Robert, Lorenne, Sénéchal, Audrey, Bocquet, Béatrice, Herbin, Laetitia, Chaudieu, Gilles, Kalatzis, Vasiliki, André, Catherine, Hamel, Christian, Physiopathologie et thérapie des déficits sensoriels et moteurs, Université Montpellier 2 - Sciences et Techniques ( UM2 ) -IFR76-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut de Génétique et Développement de Rennes ( IGDR ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -IFR140-Centre National de la Recherche Scientifique ( CNRS ), Clinique Vétérinaire Beaulieu, Institut de Génétique Moléculaire de Montpellier ( IGMM ), Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Université Montpellier 2 - Sciences et Techniques (UM2)-IFR76-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), and De Villemeur, Hervé

Subjects
Male, [SDV.GEN]Life Sciences [q-bio]/Genetics, Base Sequence, DNA Mutational Analysis, Molecular Sequence Data, [SDV.GEN] Life Sciences [q-bio]/Genetics, Sequence Analysis, DNA, Polymerase Chain Reaction, Pedigree, Disease Models, Animal, Dogs, [SDV.MHEP.OS] Life Sciences [q-bio]/Human health and pathology/Sensory Organs, rab GTP-Binding Proteins, [ SDV.MHEP.OS ] Life Sciences [q-bio]/Human health and pathology/Sensory Organs, Mutation, Animals, Female, Genetic Testing, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, [ SDV.GEN ] Life Sciences [q-bio]/Genetics, Choroideremia
Abstract

International audience; Choroideremia is an X-linked, progressive photoreceptor degeneration disorder due to mutations in CHM. In addition to an atrophy of the outer retina, affected individuals present with a characteristic atrophy of the choroid. To search for a canine model, we screened the CHM gene of 37 dogs (22 breeds) with various forms of retinal dystrophies. We found 21 variations in 13 breeds (17 detected in only one breed and 4 shared by two or more) with 43% segregating in the same pedigree, a Great Dane female and a female offspring. Of particular interest were an exonic missense variation and a 3-bp intronic deletion near a splice acceptor site. However, although not detected in unrelated healthy Great Danes, these variants were nonpathogenic since they did not segregate with the disease phenotype in the pedigree. These results suggest that a CHM dog model may not be viable, as is the case for mouse and zebrafish.

Published
2009

113. Comparative genomic mapping of uncharacterized canine retinal ESTs to identify novel candidate genes for hereditary retinal disorders

Author

Zangerl, Barbara, Johnson, Jennifer, Pillardy, Jarek, Sun, Qi, André, Catherine, Galibert, Francis, Acland, Gregory, Aguirre, Gustavo, Department of Clinical Studies, University of Pennsylvania [Philadelphia], J. A. Baker Institute, Cornell University [New York], Computational Biology Service Unit, 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), University of Pennsylvania, Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), and De Villemeur, Hervé

Subjects
MESH: Databases, Protein, MESH: Dog Diseases, MESH: Radiation Hybrid Mapping, [SDV.GEN] Life Sciences [q-bio]/Genetics, MESH: Expressed Sequence Tags, Retina, MESH: Dogs, Dogs, Retinal Diseases, MESH: Eye Proteins, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Animals, Humans, MESH: Animals, MESH: Genome, Dog Diseases, Databases, Protein, Eye Proteins, MESH: Retinal Diseases, MESH: Genome, Human, Expressed Sequence Tags, Radiation Hybrid Mapping, [SDV.GEN]Life Sciences [q-bio]/Genetics, Genome, MESH: Humans, Genome, Human, MESH: Retina, MESH: Research Design, Research Design, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Research Article
Abstract

International audience; PURPOSE: To identify the genomic location of previously uncharacterized canine retina-expressed expressed sequence tags (ESTs), and thus identify potential candidate genes for heritable retinal disorders. METHODS: A set of over 500 retinal canine ESTs were mapped onto the canine genome using the RHDF(5000-2) radiation hybrid (RH) panel, and the resulting map positions were compared to their respective localization in the CanFam2 assembly of the canine genome sequence. RESULTS: Unique map positions could be assigned for 99% of the mapped clones, of which only 29% showed significant homology to known RefSeq sequences. A comparison between RH map and sequence assembly indicated some areas of discrepancy. Retinal expressed genes were not concentrated in particular areas of the canine genome, and also were located on the canine Y chromosome (CFAY). Several of the EST clones were located within areas of conserved synteny to human retinal disease loci. CONCLUSIONS: RH mapping of canine retinal ESTs provides insight into the location of potential candidate genes for hereditary retinal disorders, and, by comparison with the assembled canine genome sequence, highlights inconsistencies with the current assembly. Regions of conserved synteny between the canine and the human genomes allow this information to be extrapolated to identify potential positional candidate genes for mapped human retinal disorders. Furthermore, these ESTs can help identify novel or uncharacterized genes of significance for better understanding of retinal morphology, physiology, and pathology.

Published
2009

114. Reactive and neoplastic hystiocytos of bernese mountain dogs : towards the identification of predisposing deries

Author

Abadie, Jérôme, Hédan, Benoît, Vilboux, Thierry, Devauchelle, Patrick, Galibert, Francis, Ostrander, Elaine, Cherel, Yan, André, Catherine, Immuno-Endocrinologie Cellulaire et Moléculaire (IECM), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire de Nantes-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR), Développement et Pathologie du Tissu Musculaire (DPTM), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Nantes, École nationale vétérinaire - Alfort (ENVA), National Institutes of Health, Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire de Nantes, 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 1 (UR1), Université de Rennes (UNIV-RENNES), and École nationale vétérinaire d'Alfort (ENVA)

Subjects
ETIOLOGIE, [SDV]Life Sciences [q-bio], HISTOLOGIE, IMMUNOLOGIE, ComputingMilieux_MISCELLANEOUS, SYSTEMIC HYSTIOCYTOSIS
Abstract

International audience

Published
2005

115. Analyse comparée des mélanomes chez le chien et l’homme

Author

Cadieu, Édouard, primary, Brito, Clotilde de, additional, Gillard, Marc, additional, Abadie, Jérôme, additional, Vergier, Béatrice, additional, Guillory, Anne-Sophie, additional, Devauchelle, Patrick, additional, Degorce, Frédérique, additional, Lagoutte, Laëtitia, additional, Hédan, Benoît, additional, Galibert, Marie-Dominique, additional, Galibert, Francis, additional, and André, Catherine, additional

Published
2014
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118. Novel origins of copy number variation in the dog genome

Author

Berglund, Jonas, Nevalainen, Elisa M, Molin, Anna-Maja, Perloski, Michele, André, Catherine, Zody, Michael C, Sharpe, Ted, Hitte, Christophe, Lindblad-Toh, Kerstin, Lohi, Hannes, Webster, Matthew T, Berglund, Jonas, Nevalainen, Elisa M, Molin, Anna-Maja, Perloski, Michele, André, Catherine, Zody, Michael C, Sharpe, Ted, Hitte, Christophe, Lindblad-Toh, Kerstin, Lohi, Hannes, and Webster, Matthew T

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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119. Identification of Genomic Regions Associated with Phenotypic Variation between Dog Breeds using Selection Mapping

Author

Broad Institute of MIT and Harvard, Sigurdsson, Snaever, Sigurdsson, Snaevar, Karlsson, Elinor K., Lindblad-Toh, Kerstin, Vaysse, Amaury, Ratnakumar, Abhirami, Derrien, Thomas, Axelsson, Erik, Pielberg, Gerli Rosengren, Fall, Tove, Seppälä, Eija H., Hansen, Mark S. T., Lawley, Cindy T., Bannasch, Danika L., Vilà, Carles, Lohi, Hannes, Galibert, Francis, Fredholm, Merete, Häggström, Jens, Hedhammar, Åke, André, Catherine, Hitte, Christophe, Webster, Matthew T., Broad Institute of MIT and Harvard, Sigurdsson, Snaever, Sigurdsson, Snaevar, Karlsson, Elinor K., Lindblad-Toh, Kerstin, Vaysse, Amaury, Ratnakumar, Abhirami, Derrien, Thomas, Axelsson, Erik, Pielberg, Gerli Rosengren, Fall, Tove, Seppälä, Eija H., Hansen, Mark S. T., Lawley, Cindy T., Bannasch, Danika L., Vilà, Carles, Lohi, Hannes, Galibert, Francis, Fredholm, Merete, Häggström, Jens, Hedhammar, Åke, André, Catherine, Hitte, Christophe, and Webster, Matthew T.

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., LUPA Consortium

Published
2012

121. Identification of genomic regions associated with phenotypic variation between dog breeds using selection mapping

Author

Vaysse, Amaury, Ratnakumar, Abhirami, Derrien, Thomas, Axelsson, Erik, Rosengren Pielberg, Gerli, Sigurdsson, Snaevar, Fall, Tove, Seppälä, Eija H, Hansen, Mark S T, Lawley, Cindy T, Karlsson, Elinor K, Bannasch, Danika, Vilà, Carles, Lohi, Hannes, Galibert, Francis, Fredholm, Merete, Häggström, Jens, Hedhammar, Ake, André, Catherine, Lindblad-Toh, Kerstin, Hitte, Christophe, Webster, Matthew Thomas, Vaysse, Amaury, Ratnakumar, Abhirami, Derrien, Thomas, Axelsson, Erik, Rosengren Pielberg, Gerli, Sigurdsson, Snaevar, Fall, Tove, Seppälä, Eija H, Hansen, Mark S T, Lawley, Cindy T, Karlsson, Elinor K, Bannasch, Danika, Vilà, Carles, Lohi, Hannes, Galibert, Francis, Fredholm, Merete, Häggström, Jens, Hedhammar, Ake, André, Catherine, Lindblad-Toh, Kerstin, Hitte, Christophe, and Webster, Matthew Thomas

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

Author

Lequarré, Anne-Sophie, Andersson, Leif, André, Catherine, Fredholm, Merete, Hitte, Christophe, Leeb, Tosso, Lohi, Hannes, Lindblad-Toh, Kerstin, Georges, Michel, Lequarré, Anne-Sophie, Andersson, Leif, André, Catherine, Fredholm, Merete, Hitte, Christophe, Leeb, Tosso, Lohi, Hannes, Lindblad-Toh, Kerstin, and Georges, Michel

Abstract

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

132. Naturally occurring melanomas in dogs as models for non-UV pathways of human melanomas

Author

Gillard, Marc, primary, Cadieu, Edouard, additional, De Brito, Clotilde, additional, Abadie, Jérôme, additional, Vergier, Béatrice, additional, Devauchelle, Patrick, additional, Degorce, Frédérique, additional, Dréano, Stephane, additional, Primot, Aline, additional, Dorso, Laetitia, additional, Lagadic, Marie, additional, Galibert, Francis, additional, Hédan, Benoit, additional, Galibert, Marie-Dominique, additional, and André, Catherine, additional

Published
2013
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139. PNPLA1 mutations cause autosomal recessive congenital ichthyosis in golden retriever dogs and humans

Author

Grall, Anaïs, primary, Guaguère, Eric, additional, Planchais, Sandrine, additional, Grond, Susanne, additional, Bourrat, Emmanuelle, additional, Hausser, Ingrid, additional, Hitte, Christophe, additional, Le Gallo, Matthieu, additional, Derbois, Céline, additional, Kim, Gwang-Jin, additional, Lagoutte, Laëtitia, additional, Degorce-Rubiales, Frédérique, additional, Radner, Franz P W, additional, Thomas, Anne, additional, Küry, Sébastien, additional, Bensignor, Emmanuel, additional, Fontaine, Jacques, additional, Pin, Didier, additional, Zimmermann, Robert, additional, Zechner, Rudolf, additional, Lathrop, Mark, additional, Galibert, Francis, additional, André, Catherine, additional, and Fischer, Judith, additional

Published
2012
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145. A canine Arylsulfatase G ( ARSG ) mutation leading to a sulfatase deficiency is associated with neuronal ceroid lipofuscinosis

Author

Abitbol, Marie, primary, Thibaud, Jean-Laurent, additional, Olby, Natasha J., additional, Hitte, Christophe, additional, Puech, Jean-Philippe, additional, Maurer, Marie, additional, Pilot-Storck, Fanny, additional, Hédan, Benoit, additional, Dréano, Stéphane, additional, Brahimi, Sandra, additional, Delattre, Delphine, additional, André, Catherine, additional, Gray, Françoise, additional, Delisle, Françoise, additional, Caillaud, Catherine, additional, Bernex, Florence, additional, Panthier, Jean-Jacques, additional, Aubin-Houzelstein, Geneviève, additional, Blot, Stéphane, additional, and Tiret, Laurent, additional

Published
2010
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148. Coat Variation in the Domestic Dog Is Governed by Variants in Three Genes

Author

Cadieu, Edouard, primary, Neff, Mark W., additional, Quignon, Pascale, additional, Walsh, Kari, additional, Chase, Kevin, additional, Parker, Heidi G., additional, VonHoldt, Bridgett M., additional, Rhue, Alison, additional, Boyko, Adam, additional, Byers, Alexandra, additional, Wong, Aaron, additional, Mosher, Dana S., additional, Elkahloun, Abdel G., additional, Spady, Tyrone C., additional, André, Catherine, additional, Lark, K. Gordon, additional, Cargill, Michelle, additional, Bustamante, Carlos D., additional, Wayne, Robert K., additional, and Ostrander, Elaine A., additional

Published
2009
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150. Genetic diversity of canine olfactory receptors

Author

Robin, Stéphanie, primary, Tacher, Sandrine, additional, Rimbault, Maud, additional, Vaysse, Amaury, additional, Dréano, Stéphane, additional, André, Catherine, additional, Hitte, Christophe, additional, and Galibert, Francis, additional

Published
2009
Full Text
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