In this thesis I report three related studies that utilise state-of-the-art technologies to investigate germline and somatic chromosomal rearrangements in humans. Firstly, 16 patients with cytogenetically detectable deletions of 3p25-p26 were analysed with high density single nucleotide polymorphism (SNP) microarrays; Affymetrix 250K SNP microarrays (n=14) and Affymetrix SNP6.0 (n=2). Assuming complete penetrance, a critical region for congenitalheart disease (CHD) susceptibility gene was refined to approximately 200 kb and a candidate critical region for mental retardation was mapped to ~1 Mb interval containing SRGAP3. Secondly, I used SNP microarray and molecular cytogenetic studies to characterize chromosome 11p15 in 8 patients with the imprinting disorder Beckwith-Wiedemann syndrome (BWS). In addition to characterising 11p duplications in three patients, the breakpoints in two patients with balanced rearrangements were mapped to two distinct regions. Thirdly, I used high resolution SNP arrays (Affymetrix 250K Sty1 and 6.0 arrays) to identify copy number changes in renal cell carcinoma (RCC) primary tumours (n=81) and cell lines (n=23). Copy number changes most frequently involved large segments (>10Mb) and loss of 3p and gain of 5q were the most common copy number changes. A comparison of copy number changes in RCC cell lines and inherited and sporadic primary tumours was made.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:528578 |
| Date | January 2011 |
| Creators | Shuib, Salwati |
| Publisher | University of Birmingham |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://etheses.bham.ac.uk//id/eprint/1339/ |
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