title: C-Nap1 mutation affects centriole cohesion and is associated with a Seckel-like syndrome in cattle.
abstract: Caprine-like Generalized Hypoplasia Syndrome (SHGC) is an autosomal-recessive disorder in Montbéliarde cattle. Affected animals present a wide range of clinical features that include the following: delayed development with low birth weight, hind limb muscular hypoplasia, caprine-like thin head and partial coat depigmentation. Here we show that SHGC is caused by a truncating mutation in the CEP250 gene that encodes the centrosomal protein C-Nap1. This mutation results in centrosome splitting, which neither affects centriole ultrastructure and duplication in dividing cells nor centriole function in cilium assembly and mitotic spindle organization. Loss of C-Nap1-mediated centriole cohesion leads to an altered cell migration phenotype. This discovery extends the range of loci that constitute the spectrum of autosomal primary recessive microcephaly (MCPH) and Seckel-like syndromes.
authors.affiliation: Institut National de la Recherche Agronomique (INRA), Unité Mixte de Recherche 1313-Génétique Animale et Biologie Intégrative (UMR1313-GABI), F-78352 Jouy-en-Josas, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Floriot
authors.affiliation: 1] Sorbonne Universités, UPMC University Paris 06, Institut de Biologie Paris Seine (IBPS)-Biologie du Développement, UMR 7622, F-75005 Paris, France [2] CNRS, UMR 7622, IBPS-Biologie du Développement, F-75005 Paris, France [3] INSERM, ERL 1156, F-75005 Paris, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Vesque
authors.affiliation: 1] Institut National de la Recherche Agronomique (INRA), Unité Mixte de Recherche 1313-Génétique Animale et Biologie Intégrative (UMR1313-GABI), F-78352 Jouy-en-Josas, France [2] Plate-forme SIGENAE/Génétique Cellulaire, INRA, Castanet-Tolosan F-31326, France.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Rodriguez
authors.affiliation: 1] Sorbonne Universités, UPMC University Paris 06, Institut de Biologie Paris Seine (IBPS)-Biologie du Développement, UMR 7622, F-75005 Paris, France [2] CNRS, UMR 7622, IBPS-Biologie du Développement, F-75005 Paris, France [3] INSERM, UMR_S 938, Saint-Antoine Research Center, F-75012 Paris, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Bourgain-Guglielmetti
authors.affiliation: 1] Sorbonne Universités, UPMC University Paris 06, Institut de Biologie Paris Seine (IBPS)-Biologie du Développement, UMR 7622, F-75005 Paris, France [2] CNRS, UMR 7622, IBPS-Biologie du Développement, F-75005 Paris, France.
authors.forename: Anthi
authors.initials: A
authors.lastname: Karaiskou
authors.affiliation: 1] Institut National de la Recherche Agronomique (INRA), Unité Mixte de Recherche 1313-Génétique Animale et Biologie Intégrative (UMR1313-GABI), F-78352 Jouy-en-Josas, France [2] Centre de Biologie pour la gestion des populations (CBGP)/INRA, UMR1031, F-34988 Montferrier-sur-Lez, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Gautier
authors.affiliation: Institut National de la Recherche Agronomique (INRA), Unité Mixte de Recherche 1313-Génétique Animale et Biologie Intégrative (UMR1313-GABI), F-78352 Jouy-en-Josas, France.
authors.forename: Amandine
authors.identifier: 0000000297132274
authors.initials: A
authors.lastname: Duchesne
authors.affiliation: INRA, Unité Expérimentale (UE0326), F-61310 LE PIN-AU-HARAS, France.
authors.forename: Sarah
authors.initials: S
authors.lastname: Barbey
authors.affiliation: 1] Institut National de la Recherche Agronomique (INRA), Unité Mixte de Recherche 1313-Génétique Animale et Biologie Intégrative (UMR1313-GABI), F-78352 Jouy-en-Josas, France [2] Allice, Département R&D, F-75595 Paris, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Fritz
authors.affiliation: Labogena, F-78352 Jouy-en-Josas, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Vasilescu
authors.affiliation: Institut National de la Recherche Agronomique (INRA), Unité Mixte de Recherche 1313-Génétique Animale et Biologie Intégrative (UMR1313-GABI), F-78352 Jouy-en-Josas, France.
authors.forename: Maud
authors.initials: M
authors.lastname: Bertaud
authors.affiliation: INRA, Unité de Virologie et Immunologie Moléculaires (UR0892), F-78352 Jouy-en-Josas, France.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Moudjou
authors.affiliation: INRA, Unité de Virologie et Immunologie Moléculaires (UR0892), F-78352 Jouy-en-Josas, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Halliez
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), Unité U1163, Université Paris Descartes-Sorbonne Paris Cité, Département de génétique, Institut Imagine, Hôpital Necker Enfants Malades, F-75015 Paris, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Cormier-Daire
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), Unité U1163, Université Paris Descartes-Sorbonne Paris Cité, Département de génétique, Institut Imagine, Hôpital Necker Enfants Malades, F-75015 Paris, France.
authors.forename: Joyce E L
authors.initials: JE
authors.lastname: Hokayem
authors.affiliation: Department Biozentrum, University of Basel, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland.
authors.forename: Erich A
authors.initials: EA
authors.lastname: Nigg
authors.affiliation: CEIA du Doubs et du Territoire de Belfort, F-25640 Roulans, France.
authors.forename: Luc
authors.initials: L
authors.lastname: Manciaux
authors.affiliation: 1] LUNAM Université, Oniris, UMR BioEpAR, CS 40706, F-44307 Nantes, France [2] INRA, UMR1300 BioEpAR, CS 40706, F-44307 Nantes, France.
authors.forename: Raphaël
authors.initials: R
authors.lastname: Guatteo
authors.affiliation: 1] LUNAM Université, Oniris, UMR BioEpAR, CS 40706, F-44307 Nantes, France [2] INRA, UMR1300 BioEpAR, CS 40706, F-44307 Nantes, France.
authors.forename: Nora
authors.initials: N
authors.lastname: Cesbron
authors.affiliation: Sorbonne Universités, UPMC University Paris 06, Paris Seine Biology Institute, Electron Microscopy Facility, F-75005 Paris, France.
authors.forename: Geraldine
authors.initials: G
authors.lastname: Toutirais
authors.affiliation: Institut National de la Recherche Agronomique (INRA), Unité Mixte de Recherche 1313-Génétique Animale et Biologie Intégrative (UMR1313-GABI), F-78352 Jouy-en-Josas, France.
authors.forename: André
authors.initials: A
authors.lastname: Eggen
authors.affiliation: 1] Sorbonne Universités, UPMC University Paris 06, Institut de Biologie Paris Seine (IBPS)-Biologie du Développement, UMR 7622, F-75005 Paris, France [2] CNRS, UMR 7622, IBPS-Biologie du Développement, F-75005 Paris, France [3] INSERM, ERL 1156, F-75005 Paris, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Schneider-Maunoury
authors.affiliation: Institut National de la Recherche Agronomique (INRA), Unité Mixte de Recherche 1313-Génétique Animale et Biologie Intégrative (UMR1313-GABI), F-78352 Jouy-en-Josas, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Boichard
authors.affiliation: 1] Sorbonne Universités, UPMC University Paris 06, Institut de Biologie Paris Seine (IBPS)-Biologie du Développement, UMR 7622, F-75005 Paris, France [2] CNRS, UMR 7622, IBPS-Biologie du Développement, F-75005 Paris, France [3] INSERM, UMR_S 938, Saint-Antoine Research Center, F-75012 Paris, France.
authors.forename: Joelle
authors.initials: J
authors.lastname: Sobczak-Thépot
authors.affiliation: 1] Institut National de la Recherche Agronomique (INRA), Unité Mixte de Recherche 1313-Génétique Animale et Biologie Intégrative (UMR1313-GABI), F-78352 Jouy-en-Josas, France [2] Allice, Département R&D, F-75595 Paris, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Schibler
mesh_terms: D000818:Animals; D002417:Cattle; D002418:Cattle Diseases / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics*; D002465:Cell Movement / Q000235:genetics*; D002502:Centrioles / Q000378:metabolism*; D017496:Hypopigmentation / Q000235:genetics / Q000662:veterinary*; D008831:Microcephaly / Q000235:genetics / Q000662:veterinary*; D009024:Morphogenesis / Q000235:genetics*; D009135:Muscular Diseases / Q000235:genetics / Q000662:veterinary*; D009154:Mutation; D013577:Syndrome
chemical_list: D018797:Cell Cycle Proteins