11 research outputs found
A Deletion in Exon 9 of the LIPH Gene Is Responsible for the Rex Hair Coat Phenotype in Rabbits (Oryctolagus cuniculus)
The fur of common rabbits is constituted of 3 types of hair differing in length and diameter while that of rex animals is essentially made up of amazingly soft down-hair. Rex short hair coat phenotypes in rabbits were shown to be controlled by three distinct loci. We focused on the âr1â mutation which segregates at a simple autosomal-recessive locus in our rabbit strains. A positional candidate gene approach was used to identify the rex gene and the corresponding mutation. The gene was primo-localized within a 40 cM region on rabbit chromosome 14 by genome scanning families of 187 rabbits in an experimental mating scheme. Then, fine mapping refined the region to 0.5 cM (Zâ=â78) by genotyping an additional 359 offspring for 94 microsatellites present or newly generated within the first defined interval. Comparative mapping pointed out a candidate gene in this 700 kb region, namely LIPH (Lipase Member H). In humans, several mutations in this major gene cause alopecia, hair loss phenotypes. The rabbit gene structure was established and a deletion of a single nucleotide was found in LIPH exon 9 of rex rabbits (1362delA). This mutation results in a frameshift and introduces a premature stop codon potentially shortening the protein by 19 amino acids. The association between this deletion and the rex phenotype was complete, as determined by its presence in our rabbit families and among a panel of 60 rex and its absence in all 60 non-rex rabbits. This strongly suggests that this deletion, in a homozygous state, is responsible for the rex phenotype in rabbits
A Deletion in Exon 9 of the LIPH Gene Is Responsible for the Rex Hair Coat Phenotype in Rabbits (Oryctolagus cuniculus)
The fur of common rabbits is constituted of 3 types of hair differing in length and diameter while that of rex animals is essentially made up of amazingly soft down-hair. Rex short hair coat phenotypes in rabbits were shown to be controlled by three distinct loci. We focused on the âr1â mutation which segregates at a simple autosomal-recessive locus in our rabbit strains. A positional candidate gene approach was used to identify the rex gene and the corresponding mutation. The gene was primo-localized within a 40 cM region on rabbit chromosome 14 by genome scanning families of 187 rabbits in an experimental mating scheme. Then, fine mapping refined the region to 0.5 cM (Zâ=â78) by genotyping an additional 359 offspring for 94 microsatellites present or newly generated within the first defined interval. Comparative mapping pointed out a candidate gene in this 700 kb region, namely LIPH (Lipase Member H). In humans, several mutations in this major gene cause alopecia, hair loss phenotypes. The rabbit gene structure was established and a deletion of a single nucleotide was found in LIPH exon 9 of rex rabbits (1362delA). This mutation results in a frameshift and introduces a premature stop codon potentially shortening the protein by 19 amino acids. The association between this deletion and the rex phenotype was complete, as determined by its presence in our rabbit families and among a panel of 60 rex and its absence in all 60 non-rex rabbits. This strongly suggests that this deletion, in a homozygous state, is responsible for the rex phenotype in rabbits
Fonctionnement hydrodynamique du lit à méandres de l'Aube
Les lits fluviaux en contexte alluvial sont considérés comme des systÚmes ouverts qui ajustent de façon quasi - permanente leur géométrie en trois dimensions en réponse aux variations dans les flux hydriques et solides. Les variables morphologiques des lits s'ajustant de façon différenciée selon les échelles de temps et d'espace, l'étude présentée a pour objectifs : de caractériser et de quantifier les changements morphologiques et morphométriques du lit fluvial de l'Aube à trois échelles (échelle séculaire, année hydrologique et crues) et de les mettre en relation avec les principales variables de contrÎle (cadre morphostructural, héritages géomorphologiques, écoulements, nature des matériaux)
Zones inondables et topographies des lits majeurs : l'exemple de l'Aube et de la Seine supérieure
Dzana Jean-Guy, Gaillard Stéphan. Zones inondables et topographies des lits majeurs : l'exemple de l'Aube et de la Seine supérieure. In: Annales de Géographie, t. 104, n°581-582, 1995. pp. 191-200
A unique case of pure lateral spinal cord herniation.
BACKGROUND: Spinal cord herniation (SCH) remains a challenging diagnosis for neuroradiologists and may require treatment challenging for neurosurgeons. Most cord herniations are usually found at anterior thoracic levels.
CLINICAL PRESENTATION: A 28-year-old woman presented at our department with a 7-year history of progressive myelopathy. MR analysis showed a displacement of the spinal cord in a lateral thoracic dural defect. The herniated cord was released using a microscope and the patient significantly recovered 6 months after surgery.
CONCLUSION: We present a unique case of pure lateral SCH. In the light of reviewed literature and operative findings, the underlying pathophysiological mechanisms are discussed.[Cas unique dâhernie mĂ©dullaire trans-durale strictement latĂ©rale] CONTEXTE : Les hernies mĂ©dullaires trans-durales restent de diagnostic difficile pour le neuroradiologue et leur traitement constitue un challenge pour le neurochirurgien. La plupart des hernies mĂ©dullaires sont situĂ©es dans un dĂ©fect dural antĂ©rieur, au niveau du rachis thoracique.
PRĂSENTATION CLINIQUE : Une patiente de 28 ans sâest prĂ©sentĂ©e dans le service de neurochirurgie avec un tableau clinique de myĂ©lopathie, de dĂ©veloppement lentement progressif sur une pĂ©riode de 7 ans. LâIRM mĂ©dullaire a montrĂ© une incarcĂ©ration du cordon mĂ©dullaire thoracique dans un dĂ©fect dural strictement latĂ©ral. La moelle Ă©piniĂšre a Ă©tĂ© libĂ©rĂ©e chirurgicalement, sous microscope. LâĂ©tat neurologique de la patiente sâest significativement amĂ©liorĂ© 6 mois aprĂšs lâintervention.
CONCLUSION : Nous prĂ©sentons un cas unique dâhernie mĂ©dullaire trans-durale strictement latĂ©rale. Ă la lumiĂšre des donnĂ©es de la littĂ©rature et de nos constatations opĂ©ratoires, les mĂ©canismes physiopathologiques sous-jacents sont discutĂ©s
Menez-Dregan 1 (Plouhinec, FinistÚre, France) : un site d'habitat du Paléolithique inférieur en grotte marine. Stratigraphie, structures de combustion, industries riches en galets aménagés [Menez-Dregan 1 (Plouhinec, FinistÚre, France): A Lower Paleolithic site in a marine cave. Stratigraphy, structures of combustion, lithic industry with cobble tools]
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Hypermethylator Phenotype and Ectopic GIP Receptor in GNAS Mutation-Negative Somatotropinomas
Abstract Context Besides GNAS gene mutations, the molecular pathogenesis of somatotroph adenomas responsible for gigantism and acromegaly remains elusive. Objective To investigate alternative driver events in somatotroph tumorigenesis, focusing on a subgroup of acromegalic patients with a paradoxical increase in growth hormone (GH) secretion after oral glucose, resulting from ectopic glucose-dependent insulinotropic polypeptide receptor (GIPR) expression in their somatotropinomas. Design, Setting, and Patients We performed combined molecular analyses, including array-comparative genomic hybridization, RNA/DNA fluorescence in situ hybridization, and RRBS DNA methylation analysis on 41 somatotropinoma samples from 38 patients with acromegaly and three sporadic giants. Ten patients displayed paradoxical GH responses to oral glucose. Results GIPR expression was detected in 13 samples (32%), including all 10 samples from patients with paradoxical GH responses. All GIPR-expressing somatotropinomas were negative for GNAS mutations. GIPR expression occurred through transcriptional activation of a single allele of the GIPR gene in all GIPR-expressing samples, except in two tetraploid samples, where expression occurred from two alleles per nucleus. In addition to extensive 19q duplications, we detected in four samples GIPR locus microamplifications in a certain proportion of nuclei. We identified an overall hypermethylator phenotype in GIPR-expressing samples compared with GNAS-mutated adenomas. In particular, we observed hypermethylation in the GIPR gene body, likely driving its ectopic expression. Conclusions We describe a distinct molecular subclass of somatotropinomas, clinically revealed by a paradoxical increase of GH to oral glucose related to pituitary GIPR expression. This ectopic GIPR expression occurred through hypomorphic transcriptional activation and is likely driven by GIPR gene microamplifications and DNA methylation abnormalities
Regulation of RNA polymerase III transcription during transformation of human IMR90 fibroblasts with defined genetic elements
Regulation of RNA polymerase III transcription during transformation of human IMR90 fibroblasts with defined genetic elements
<p>RNA polymerase (Pol) III transcribes small untranslated RNAs that are essential for cellular homeostasis and growth. Its activity is regulated by inactivation of tumor suppressor proteins and overexpression of the oncogene c-MYC, but the concerted action of these tumor-promoting factors on Pol III transcription has not yet been assessed. In order to comprehensively analyse the regulation of Pol III transcription during tumorigenesis we employ a model system that relies on the expression of five genetic elements to achieve cellular transformation. Expression of these elements in six distinct transformation intermediate cell lines leads to the inactivation of TP53, RB1, and protein phosphatase 2A, as well as the activation of RAS and the protection of telomeres by TERT, thereby conducting to full tumoral transformation of IMR90 fibroblasts. Transformation is accompanied by moderately enhanced levels of a subset of Pol III-transcribed RNAs (7SK; MRP; H1). In addition, mRNA and/or protein levels of several Pol III subunits and transcription factors are upregulated, including increased protein levels of TFIIIB and TFIIIC subunits, of SNAPC1 and of Pol III subunits. Strikingly, the expression of POLR3G and of SNAPC1 is strongly enhanced during transformation in this cellular transformation model. Collectively, our data indicate that increased expression of several components of the Pol III transcription system accompanied by a 2-fold increase in steady state levels of a subset of Pol III RNAs is sufficient for sustaining tumor formation.</p