0000000000077698

AUTHOR

Dorus A. Mans

showing 4 related works from this author

Usher syndrome and Leber congenital amaurosis are molecularly linked via a novel isoform of the centrosomal ninein-like protein.

2009

Contains fulltext : 80984.pdf (Publisher’s version ) (Closed access) Usher syndrome (USH) and Leber congenital amaurosis (LCA) are autosomal recessive disorders resulting in syndromic and non-syndromic forms of blindness. In order to gain insight into the pathogenic mechanisms underlying retinal degeneration, we searched for interacting proteins of USH2A isoform B (USH2A(isoB)) and the LCA5-encoded protein lebercilin. We identified a novel isoform of the centrosomal ninein-like protein, hereby named Nlp isoform B (Nlp(isoB)), as a common interactor. Although we identified the capacity of this protein to bind calcium with one of its three EF-hand domains, the interacton with USH2A(isoB) did …

Gene isoformRetinal degenerationCandidate geneGenetics and epigenetic pathways of disease [NCMLS 6]Usher syndromeMolecular Sequence DataOptic Atrophy Hereditary LeberBiologyIn Vitro TechniquesNeuroinformatics [DCN 3]CiliopathiesRetinaCell LineMiceCiliogenesisTwo-Hybrid System TechniquesGeneticsmedicineotorhinolaryngologic diseasesAnimalsHumansProtein IsoformsPhotoreceptor CellsAmino Acid SequenceNuclear proteinRats WistarEye ProteinsMolecular BiologyGenetics (clinical)GeneticsExtracellular Matrix ProteinsCiliumNuclear ProteinsGeneral MedicineArticlesmedicine.diseaseRatsMice Inbred C57BLMicrotubule-Associated ProteinsSequence AlignmentUsher SyndromesFunctional Neurogenomics [DCN 2]Protein BindingHuman Molecular Genetics
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CiliaCarta: An integrated and validated compendium of ciliary genes

2019

The cilium is an essential organelle at the surface of mammalian cells whose dysfunction causes a wide range of genetic diseases collectively called ciliopathies. The current rate at which new ciliopathy genes are identified suggests that many ciliary components remain undiscovered. We generated and rigorously analyzed genomic, proteomic, transcriptomic and evolutionary data and systematically integrated these using Bayesian statistics into a predictive score for ciliary function. This resulted in 285 candidate ciliary genes. We generated independent experimental evidence of ciliary associations for 24 out of 36 analyzed candidate proteins using multiple cell and animal model systems (mouse…

ProteomicsSensory ReceptorsNematodaSocial SciencesCiliopathiesBiochemistrySensory disorders Donders Center for Medical Neuroscience [Radboudumc 12]Transcriptome0302 clinical medicineAnimal CellsPsychologyRETINAL PHOTORECEPTOR CELLSExomeNeurons0303 health sciences030302 biochemistry & molecular biologyEukaryotaGenomicsPRIMARY CILIUMthecilium3. Good healthNucleic acidsGenetic interferenceOsteichthyesMedicineEpigeneticsCellular Structures and OrganellesCellular Typesproteomic databasesSensory Receptor CellsScienceeducationCiliary genesLEBER CONGENITAL AMAUROSISGenomics03 medical and health sciencesGeneticsCiliaCaenorhabditis elegansIDENTIFICATIONMUTATIONSEmbryosciliaOrganismsBiology and Life SciencesBayes TheoremMolecular Sequence Annotationmedicine.diseaseInvertebratesFishciliary proteomeAnimal StudiesCaenorhabditisGene expressionembryos030217 neurology & neurosurgeryDevelopmental BiologyNeurosciencePhotoreceptorsCandidate geneEmbryologyOligonucleotidesMorpholinoDatabase and Informatics MethodsRNA interferenceBayesian classifierTRANSITION ZONEZebrafishAntisense OligonucleotidesZebrafishGeneticsMultidisciplinarySpectrometric Identification of ProteinsProteomic DatabasesNucleotidesCiliumQStable Isotope Labeling by Amino Acids in Cell CultureRphotoreceptorsMetabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6]Animal ModelsPhenotypeINTRAFLAGELLAR TRANSPORTDIFFERENTIATIONPhenotypeExperimental Organism SystemsCaenorhabditis ElegansVertebratesSensory PerceptionResearch ArticleSignal TransductionEXPRESSIONStable isotope labeling by amino acids in cell cultureComputational biologyBiologyResearch and Analysis MethodsSOLUTE-CARRIER-PROTEINModel OrganismsmedicineAnimalsdata integration030304 developmental biologyAfferent NeuronsReproducibility of ResultsCell Biologyzebrafishbiology.organism_classificationCiliopathyRenal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11]Biological DatabasesCellular NeuroscienceRNAOSCP1CiliaCartaPLoS ONE
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A high-throughput genome-wide siRNA screen for ciliogenesis identifies new ciliary functional components and ciliopathy genes.

2015

Defects in primary cilium biogenesis underlie the ciliopathies, a growing group of genetic disorders. We describe the first whole genome siRNA-based reverse genetics screen for defects in biogenesis and/or maintenance of the primary cilium, obtaining a global resource for investigation and interventions into the processes that are critical for the ciliary system. In total, we identified 83 candidate ciliogenesis and ciliopathy genes, including 15 components of the ubiquitin-proteasome system. The validated hits also include 12 encoding G-protein-coupled receptors, and three encoding pre-mRNA processing factors (PRPF6, PRPF8 and PRPF31) mutated in autosomal dominant retinitis pigmentosa. Com…

GeneticsCandidate genePRPF31CiliumCell BiologyBiologymedicine.diseaseCiliopathiesHuman geneticsCiliopathyCiliogenesismedicineOral PresentationExome sequencing
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An siRNA-based functional genomics screen for the identification of regulators of ciliogenesis and ciliopathy genes

2015

Item does not contain fulltext Defects in primary cilium biogenesis underlie the ciliopathies, a growing group of genetic disorders. We describe a whole-genome siRNA-based reverse genetics screen for defects in biogenesis and/or maintenance of the primary cilium, obtaining a global resource. We identify 112 candidate ciliogenesis and ciliopathy genes, including 44 components of the ubiquitin-proteasome system, 12 G-protein-coupled receptors, and 3 pre-mRNA processing factors (PRPF6, PRPF8 and PRPF31) mutated in autosomal dominant retinitis pigmentosa. The PRPFs localize to the connecting cilium, and PRPF8- and PRPF31-mutated cells have ciliary defects. Combining the screen with exome sequen…

PRPF31Pregnancy ProteinsInbred C57BLCiliopathiesMiceImmunologicCerebellumDatabases GeneticEye AbnormalitiesNon-U.S. Gov'tZebrafishExome sequencingMice KnockoutGeneticsResearch Support Non-U.S. Gov'tCiliumHigh-Throughput Nucleotide SequencingMetabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6]GenomicsKidney Diseases CysticPhenotypeKidney DiseasesRNA InterferenceAbnormalitiesMultipleFunctional genomicsCiliary Motility DisordersGenetic MarkersEllis-Van Creveld SyndromeKnockoutJeune syndromeOther Research Radboud Institute for Molecular Life Sciences [Radboudumc 0]BiologyResearch SupportTransfectionRetinaArticlewhole-genome siRNA screenJoubert syndromeN.I.H.DatabasesCysticreverse geneticsResearch Support N.I.H. ExtramuralGeneticCerebellar DiseasesJoubert syndromeCiliogenesisSuppressor FactorsJournal ArticleSuppressor Factors ImmunologicmedicineAnimalsHumansAbnormalities MultipleGenetic Predisposition to DiseasePhotoreceptor CellsCiliaGenetic TestingCaenorhabditis elegansExtramuralMembrane ProteinsProteinsReproducibility of ResultsCell Biologymedicine.diseaseMice Inbred C57BLCytoskeletal ProteinsCiliopathyRenal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11]HEK293 CellsMutationciliopathiesGenome-Wide Association StudyNature Cell Biology
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