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An analysis of the molecular basis of the 22q11 deletion syndrome

Prescott, Katrina Rachel; (2006) An analysis of the molecular basis of the 22q11 deletion syndrome. Doctoral thesis , UCL (University College London). Green open access

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The 22qll deletion syndrome (22qllDS) is a developmental syndrome of the pharyngeal region. Tbxl haploinsufficiency is thought to account for the main structural anomalies observed in the 22ql 1 deletion syndrome. The "Dfl" deletion in the mouse provides a model of 22ql IDS, the deletion reflecting Tbxl haploinsufficiency in the context of the deletion of 21 adjacent genes. The aims of this study were to examine genes within the Tbxl pathway. This was initiated by various experimental approaches including yeast two hybrid and Affymetrix expression microarray analysis. Initially a yeast two hybrid screen was conducted using the mouse Tbxl protein as bait, to determine potential protein binding partners for Tbxl. Using the N terminus of Tbxl four independent clones of the cytoplasmic dynein light chain 1 protein were identified. This protein is a potential Tbxl interactor and the implications of this and future follow-up work are discussed. Secondly an Affymetrix microarray screen was conducted using RNA from pooled branchial arch dissections of El0.5 Dfl and wild type embryos. Dfl and wild type RNA were hybridised and the data were analysed using the Genespring statistical computer program. Potential upregulated and downregulated targets were identified and some were verified using real time quantitative PCR and whole mount in situ hybridisation. A similar study was performed using RNA from Pax3 homozygous and heterozygous embryos to exam dysregulated genes from a mouse model with a similar phenotype to 22ql IDS. Finally to examine the possibility of related pathways implicated in 22qllDS pathogenesis an array-comparative genomic hybridisation (array-CGH) study was performed in collaborated with Prof Nigel Carter at the Sanger institute by analysing DNA from patients with features of 22qllDS, but no deletion within the DiGeorge region on chromosome 22qll. Three patients with chromosomal imbalances were identified and two were confirmed by FISH and microsatellite analysis.

Type: Thesis (Doctoral)
Title: An analysis of the molecular basis of the 22q11 deletion syndrome
Identifier: PQ ETD:593123
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest. Third party copyright material has been removed from the ethesis. Images identifying individuals have been redacted or partially redacted to protect their identity.
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
URI: https://discovery.ucl.ac.uk/id/eprint/1445799
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