A 3.7 Mb deletion encompassing ZEB2 causes a novel polled and multisystemic syndrome in the progeny of a somatic mosaic bull
| Autor: | Brigitte Marquant-Le Guienne, Hélène Hayes, Guy Noé, Cécile Grohs, Claire Ponsart, Laetitia Clément, Arnaud Delpeuch, Eric Pailhoux, Aurélie Auguste, Marie-Noelle Rossignol, Olivier Bouchez, Aurélien Capitan, Didier Boichard, Laura Salas-Cortes, Stéphane Chaffaux, Maëlle Pannetier, Sarah Barbey, Christophe Klopp, Cécile Donnadieu, Yves Gallard, Marie-Christine Deloche, Diane Esquerre, Harmonie Barasc, Daniel Le Bourhis, Dominique Dozias, Eric Venot, Stephan Bouet, Alain Pinton, Céline Chantry-Darmon, Emeline Lhuilier, Gerald Salin, Bernard Weiss, Emilie Cobo, Aurélie Allais-Bonnet |
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| Přispěvatelé: | Génétique Animale et Biologie Intégrative (GABI), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Biologie du Développement et Reproduction (BDR), Institut National de la Recherche Agronomique (INRA), Laboratoire de Génétique Cellulaire (LGC), Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Département Recherche et Développement, Union Nationale des Coopératives Agricoles d'Elevage et d'Insémination Animale, Département Génétique, Identification, Phénotypes et Systèmes d'Information en Elevage, Institut de l'Elevage, Laboratoire d'Analyse Génétique pour les Espèces Animales (LABOGENA), Domaine expérimental animal du Pin (SEA), Unité de Biométrie et Intelligence Artificielle (UBIA), This project was funded by Apis Gène 'Hornout' and INRA-DGA 'Hornaseq' grants., Biologie du développement et reproduction (BDR), École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Union nationale des coopératives d’élevage et d’insémination animale (UNCEIA), Institut de l'élevage (IDELE), AgroParisTech-Institut National de la Recherche Agronomique (INRA) |
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Male
[SDV.SA]Life Sciences [q-bio]/Agricultural sciences corne Anatomy and Physiology bovin Somatic cell Digestive Physiology Inheritance Patterns Skin Anatomy lcsh:Medicine Veterinary Anatomy and Physiology Animal Digestive Anatomy Cardiovascular Cardiovascular System Digestive Anatomy Loss of heterozygosity Animal Musculoskeletal Anatomy Pregnancy Reproductive Physiology lcsh:Science Base Pairing Musculoskeletal System Musculoskeletal Anatomy Horns Sequence Deletion Skin Genetics 0303 health sciences Multidisciplinary Mosaicism Congenital Heart Disease Chromosome Mapping Obstetrics and Gynecology Embryo Syndrome 04 agricultural and veterinary sciences Premature ovarian failure Autosomal Dominant symbols Medicine Female Genital Anatomy Research Article Cattle Diseases Locus (genetics) Gastroenterology and Hepatology Biology Real-Time Polymerase Chain Reaction 03 medical and health sciences symbols.namesake Fetus Animal Genital Anatomy medicine Animals Humans Abnormalities Multiple Gene 030304 developmental biology Clinical Genetics lcsh:R Reproductive System 0402 animal and dairy science Wild type medicine.disease 040201 dairy & animal science Repressor Proteins Animal Skin Anatomy Mutation Cardiovascular Anatomy Mendelian inheritance Cattle Veterinary Science lcsh:Q Digestive System |
| Zdroj: | PLoS ONE PLoS ONE, Public Library of Science, 2012, 7, online (11), Non paginé. ⟨10.1371/journal.pone.0049084⟩ PLoS ONE, Vol 7, Iss 11, p e49084 (2012) Plos One 11 (7, online), Non paginé. (2012) |
| ISSN: | 1932-6203 |
| Popis: | Polled and Multisystemic Syndrome (PMS) is a novel developmental disorder occurring in the progeny of a single bull. Its clinical spectrum includes polledness (complete agenesis of horns), facial dysmorphism, growth delay, chronic diarrhea, premature ovarian failure, and variable neurological and cardiac anomalies. PMS is also characterized by a deviation of the sex-ratio, suggesting male lethality during pregnancy. Using Mendelian error mapping and whole-genome sequencing, we identified a 3.7 Mb deletion on the paternal bovine chromosome 2 encompassing ARHGAP15, GTDC1 and ZEB2 genes. We then produced control and affected 90-day old fetuses to characterize this syndrome by histological and expression analyses. Compared to wild type individuals, affected animals showed a decreased expression of the three deleted genes. Based on a comparison with human Mowat-Wilson syndrome, we suggest that deletion of ZEB2, is responsible for most of the effects of the mutation. Finally sperm-FISH, embryo genotyping and analysis of reproduction records confirmed somatic mosaicism in the founder bull and male-specific lethality during the first third of gestation. In conclusion, we identified a novel locus involved in bovid horn ontogenesis and suggest that epithelial-to-mesenchymal transition plays a critical role in horn bud differentiation. We also provide new insights into the pathogenicity of ZEB2 loss of heterozygosity in bovine and humans and describe the first case of male-specific lethality associated with an autosomal locus in a non-murine mammalian species. This result sets PMS as a unique model to study sex-specific gene expression/regulation. |
| Databáze: | OpenAIRE |
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