The characterization and potential functional role of wdr81, a novel zebrafish gene, associated with cerebellar ataxia, mental retardation and dysequilibrium syndrome (camrq) in humans

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buir.advisorÖzçelik, Tayfun
dc.contributor.authorDoldur Ballı, Füsun
dc.date.accessioned2016-05-10T13:00:34Z
dc.date.available2016-05-10T13:00:34Z
dc.date.copyright2016-04
dc.date.issued2016-04
dc.date.submitted2016-05-10
dc.descriptionCataloged from PDF version of thesis.en_US
dc.descriptionIncludes bibliographical references (leaves 90-110).en_US
dc.descriptionThesis (Ph. D.): Bilkent University, Department of Molecular Biology and Genetics, İhsan Doğramacı Bilkent University, 2016.en_US
dc.description.abstractCerebellar ataxia, mental retardation and dysequilibrium syndrome (CAMRQ) is a neurodevelopmental disorder. The gene encoding WD repeat containing protein 81 (WDR81) was reported to be associated with CAMRQ2 [MIM 610185]. Human and mouse studies indicated the potential importance of WDR81 in neurodevelopment. The first aim in this study was to characterize the transcript and to reveal the expression profile of wdr81 in zebrafish. The second aim was to perform the initial characterization of wdr81 morphants. In silico analysis indicated that the conserved domains are shared in human, mouse and zebrafish orthologous proteins, implying a conserved function of WDR81 in three species. The characterization of the transcript revealed that wdr81 possessed one ORF and one 5’UTR structure. The predicted sequence for 3’UTR was confirmed along with detection of some variants and an insertion site in samples from ten developmental timepoints and in several adult tissues. This region was not detected in kidney, intestine and gills, which might be pointing out an alternative polyadenylation event. wdr81 appeared to be maternally supplied. 5 hpf and 18 hpf were detected as crucial timepoints regarding wdr81 expression. Expression of wdr81 was found to be increased in the eye and brain regions at 18 hpf and 48 hpf. wdr81 was found to be ubiquitously expressed in the adult zebrafish. The expression of wdr81 in the adult brain and eye was detected in several regions including retinal layers, presumptive Purkinje cells and some proliferative zones. The splice blocking morpholino which targets the exon 2-intron 2 junction of wdr81 worked at 3 tested doses; 2 ng, 4 ng and 8 ng. The effect of the wdr81 morpholino was detected to add the intron, which is downstream of the target exon, to the transcript and introduce a stop codon. Preliminary results indicated a significant reduction in the head sizes at a ratio of 3.88% (p:0.027) in the wdr81 morphant group compared to uninjected group and gbx2 expression was observed to be higher in wdr81 morphants compared to the control groups. In short, findings of this study emphasize the significance of wdr81 in neurodevelopment and suggest a potential role in neuronal proliferation. This study also serves as a basis for future functional studies.en_US
dc.description.provenanceSubmitted by Betül Özen (ozen@bilkent.edu.tr) on 2016-05-10T13:00:34Z No. of bitstreams: 1 FusunDoldurBalli-DoktoraTezi.pdf: 3688802 bytes, checksum: 59f7eeac92e98bacfd7fe4e19647fe5e (MD5)en
dc.description.provenanceMade available in DSpace on 2016-05-10T13:00:34Z (GMT). No. of bitstreams: 1 FusunDoldurBalli-DoktoraTezi.pdf: 3688802 bytes, checksum: 59f7eeac92e98bacfd7fe4e19647fe5e (MD5) Previous issue date: 2016-04en
dc.description.statementofresponsibilityby Füsun Doldur Ballı.en_US
dc.embargo.release2018-05-10
dc.format.extentxvii, 131 leaves : illustrations, charts.en_US
dc.identifier.itemidB153161
dc.identifier.urihttp://hdl.handle.net/11693/29091
dc.language.isoEnglishen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectWdr81en_US
dc.subjectZebrafishen_US
dc.subjectRACEen_US
dc.subjectGene expressionen_US
dc.subjectMorpholinoen_US
dc.titleThe characterization and potential functional role of wdr81, a novel zebrafish gene, associated with cerebellar ataxia, mental retardation and dysequilibrium syndrome (camrq) in humansen_US
dc.title.alternativeİnsanlardaki serebellar ataksi, zeka geriliği ve dengesizlik sendromu ile ilişkilendirilen ve zebrabalığında yeni bir gen olan wdr81’in karakterizasyonu ve muhtemel işlevsel rolüen_US
dc.typeThesisen_US
thesis.degree.disciplineMolecular Biology and Genetics
thesis.degree.grantorBilkent University
thesis.degree.levelDoctoral
thesis.degree.namePh.D. (Doctor of Philosophy)

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