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Title: Organisation of the mammalian genome in the nucleus
Author: Mahy, Nicola L.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2001
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To determine whether genes occupy specific sites within interphase chromosome territories, I have used 2D and 3D fluorescence in situ hybridisation (FISH) to investigate the spatial organisation of stretches of DNA from the short arm of human chromosome 11 (HSA11p), which differ in gene content. I found that gene sequences contained in 1Mb of DNA from the moderately gene-rich WAGR (Wilms’ tumour, aniridia, genitourinary, mental retardation syndrome) locus of 11p13 are not localised at the periphery of the interphase HSA11p territory as compared to intergenic, non-expressed sequences from the same region. The entire locus is positioned approximately one third of the way along the radius of the HSA11p domain. The organisation of this 1mb of DNA remains unchanged in cell lines expressing different combinations of genes, indicating that transcriptional status does not play a significant role in the interphase positioning of this locus in human cell lines. In contrast, I found that DNA from gene-rich 11p15.5 adopts an unusual configuration in the interphase nucleus. Sequences from this region appear to localise outside of the main body of the HSA11p territory. I have examined possible explanations for this extrusion of chromatin from the chromosome domain. It is not characteristic of all chromatin containing telomere sequences, neither is it characteristic of all loci subject to imprinting. However, the extrusion of chromatin from a chromosome territory appears to be characteristic of gene-rich regions of the human genome. A recent study of the gene-rich MHC locus on chromosome 6 observed looping of chromatin from this region and found its incidence to be transcription dependent. The publication of the complete sequence of chromosomes HSA21 and HSA22 provided the ideal tool to further test the hypothesis that gene-density plays a role in the organisation of chromatin.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available