Characterization of the ovine ribosomal protein SA gene and its pseudogenes

Background: The ribosomal protein SA (RPSA), previously named 37-kDa laminin receptor precursor/67-kDa laminin receptor (LRP/LR) is a multifunctional protein that plays a role in a number of pathological processes, such as cancer and prion diseases. In all investigated species, RPSA is a member of a multicopy gene family consisting of one full length functional gene and several pseudogenes. Therefore, for studies on RPSA related pathways/pathologies, it is important to characterize the whole family and to address the possible function of the other RPSA family members. The present work aims at deciphering the RPSA family in sheep. Results: In addition to the full length functional ovine RPSA gene, 11 other members of this multicopy gene family, all processed pseudogenes, were identified. Comparison between the RPSA transcript and these pseudogenes shows a large variety in sequence identities ranging from 99% to 74%. Only one of the 11 pseudogenes, i.e. RPSAP7, shares the same open reading frame (ORF) of 295 amino acids with the RPSA gene, differing in only one amino acid. All members of the RPSA family were annotated by comparative mapping and fluorescence in situ hybridization (FISH) localization. Transcription was investigated in the cerebrum, cerebellum, spleen, muscle, lymph node, duodenum and blood, and transcripts were detected for 6 of the 11 pseudogenes in some of these tissues. Conclusions: In the present work we have characterized the ovine RPSA family. Our results have revealed the existence of 11 ovine RPSA pseudogenes and provide new data on their structure and sequence. Such information will facilitate molecular studies of the functional RPSA gene taking into account the existence of these pseudogenes in the design of experiments. It remains to be investigated if the transcribed members are functional as regulatory non-coding RNA or as functional proteins

C-Nap1 mutation affects centriole cohesion and is associated with a Seckel-like syndrome in cattle

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

Molecular genetic analysis of the MHC in an ELA-typed horse family

Chantier qualité spécifique "Auteurs Externes" département de Génétique animale : uniquement liaison auteur au référentiel HR-AccessInternational audienc

Molecular genetic analysis of the major histocompatibility complex in an ELA typed horse family

Chantier qualité spécifique "Auteurs Externes" département de Génétique animale : uniquement liaison auteur au référentiel HR-AccessInternational audienc

Porcine and bovine centromeric and pericentromeric sequences

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Centromeric/pericentromeric junction within the MHC locus on chromosome 7 in pig

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General framework of the rabbit histocompatibility complex

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Séquences centromériques porcines et bovines

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Du phénotype à la mutation causale : le cas des anomalies récessives bovines

Cet article présente la méthodologie utilisée pour identifier la mutation responsable d’une anomalie génétique à partir de cas d’animaux affectés. Dans un premier temps, une collection de cas aussi homogènes que possible est constituée, de la même race et avec les mêmes signes cliniques, complétée par une population témoin apparentée mais non atteinte. Une analyse de pedigree est possible pour rechercher l’ancêtre commun qui a pu transmettre l’anomalie à chacun des cas. Le génotypage par puce permet de mettre en évidence très rapidement une petite région du génome homozygote et identique à tous les marqueurs qui contient la mutation recherchée. La mutation est ensuite identifiée par séquençage du génome de quelques cas, filtrage des variants observés sur la base d’une part, de leur présence chez d’autres animaux, et d’autre part, de leur annotation fonctionnelle. Une validation statistique est ensuite pratiquée par génotypage à grande échelle, pour vérifier l’association totale entre génotype et phénotype. Enfin, la causalité de la mutation est étudiée par analyse fonctionnelle, incluant l’analyse des ARN et des protéines, l’imagerie cellulaire, voire la création de modèles transgéniques.This article presents the methodology used to identify the mutation responsible for a genetic defect from the observation of cases. In the first step, a set of homogeneous cases are collected, from the same breed and with the same clinical signs. This collection is completed by a related but unaffected control population. A pedigree analysis is possible to point towards a common ancestor who may have transmitted the defect to all cases. A genotyping step using a SNP chip is used to display a small genomic region homozygous and identical at all markers and including the mutation. The mutation is then identified by genome sequencing of a few cases followed by the filtering of the variants against a large sequence database of unaffected animals. The best candidate variants are retained on the basis of their functional annotation. The mutation is then statistically confirmed on the basis of large scale genotyping, to verify the complete association between the mutation and the phenotype. Finally, the causality of the mutation is proven by functional analysis, including RNA and protein analysis, cellular imaging, and even through transgenic models carrying the mutation

133 new gene localizations on the rabbit cytogenetic map

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