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dc.contributor.advisorParacchini, Silvia
dc.contributor.advisorSillar, Keith T. (Keith Thomas)
dc.contributor.authorGostić, Monika
dc.coverage.spatial274 p.en_US
dc.date.accessioned2018-11-14T10:52:25Z
dc.date.available2018-11-14T10:52:25Z
dc.date.issued2018-12-06
dc.identifier.urihttp://hdl.handle.net/10023/16446
dc.description.abstractDyslexia is a neurodevelopmental disorder that affects between 5% and 12% of school-aged children. Individuals with dyslexia have difficulties in learning to read despite normal IQ levels and adequate socio-economical and educational opportunities. Dyslexia has a strong genetic component, but only a few candidate genes have been characterized to date. The KIAA0319 gene is a strong dyslexia candidate found to be associated with dyslexia in independent studies. The KIAA0319 genetic variants associated with dyslexia reside in a regulatory region. Studies in rat suggested that this gene is required for neuronal migration during early cortex formation. The KIAA0319-like (KIAA0319L) is a KIAA0319 homolog in structure and has recently been shown to play a role in dyslexia. I used zebrafish as a model organism both to study the effects of non-coding variants and to characterise kiaa0319 gene function. I used Gateway Tol2 technology to study the role of regulatory sequences. While these experiments led to inconclusive results, they highlighted some of the challenges but also the feasibility of using zebrafish as model organism to study genetic associations. In parallel, I studied the kiaa0319 function with knockout and knockdown experiments. Additionally, I conducted a detailed gene expression analysis with different in situ hybridisation protocols showing kiaa0319 ubiquitous expression in the whole embryo before 12 hours post fertilisation, with later specification to the eyes, brain, otic vesicle and notochord. Additionally, I have tested for the expression of kiaa0319l and showed similar expression pattern to the kiaa0319, but with significantly lower expression of kiaa0319l in zebrafish notochord. My data show, for the first time, that kiaa0319 has stage-specific expression in the brain and notochord during zebrafish early development, suggesting kiaa0319 specific role in the development of these structures. These results are in line with recent mouse studies. With this project I support the idea of kiaa0319 role being extended beyond the brain function and propose a role for kiaa03019 in the visual system and in the notochord.en_US
dc.language.isoenen_US
dc.publisherUniversity of St Andrews
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectZebrafishen_US
dc.subjectNotochorden_US
dc.subjectkiaa0319en_US
dc.subjectNeurodevelopmenten_US
dc.subjectDyslexiaen_US
dc.subjectTol2en_US
dc.subjectIn situ hybridizationen_US
dc.subjectGeneticsen_US
dc.subjectkiaa0319len_US
dc.subject.lccQL638.C94G7
dc.subject.lcshZebra danio--Geneticsen
dc.subject.lcshZebra danio--Behavioren
dc.subject.lcshDevelopmental neurobiology--Researchen
dc.titleZebrafish as a model to study genes associated with neurodevelopmental disordersen_US
dc.typeThesisen_US
dc.type.qualificationlevelDoctoralen_US
dc.type.qualificationnamePhD Doctor of Philosophyen_US
dc.publisher.institutionThe University of St Andrewsen_US
dc.rights.embargodate2021-10-31
dc.rights.embargodateThesis restricted in accordance with University regulations. Print and electronic copy restricted until 31st October 2021en


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