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Title: Telomere length and distribution in three developmental stages
Author: Turner, Kara Jane
ISNI:       0000 0004 5362 3236
Awarding Body: University of Kent
Current Institution: University of Kent
Date of Award: 2015
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Telomeres are specialised nucleoprotein structures present at the ends of each chromatid that function to maintain genome stability. It is well established that a gradual decline in telomere length is associated with the process of cellular ageing, and thereby to the pathobiology of age-related diseases. In addition, the localisation of the telomere at the nuclear periphery plays an important role in the spatio-temporal organisation of the genome and in ensuring faithful segregation of chromosomes during meiosis. The aims of this thesis were to investigate telomere localisation in the nucleus, and telomere length in three hitherto early stages of development, gametogenesis, preimplantation embryogenesis and the neonatal period. Specifically: 1. To test the hypothesis that telomeres localised at the nuclear periphery in sperm cells and that this organisation was altered in sub-fertile men 2. To optimise a means of assessing average telomere length using DNA from small sample sizes and using whole genome amplified DNA from single cells 3. To investigate the role of telomere length in reproductive ageing and aneuploidy generation in women by testing the hypothesis that telomere length is significantly shorter in the first polar bodies and cleavage stage embryos of older women 4. To test the hypothesis that “preterm at term” babies (i.e. premature babies assessed at the time of their due date) displayed genetic signs of premature ageing (as manifested by significantly shorter telomeres than their term born counterparts) alongside the already established clinical signs (characterised by hypertension, diabetes and altered body fat distribution) Results confirmed the peripheral distribution of telomeres in the sperm heads of normally fertile males (using both 2D and 3D imaging) plus the novel finding that telomere distribution patterns are altered in the sperm heads of infertile males. Secondly, a reliable means of measuring telomere length was optimised in order to assess average telomere length using DNA from small sample volumes (down to single cells). Using this technology, average telomere length analysis in polar bodies and embryos found no evidence to support the hypothesis that telomere length is associated with either advanced maternal age or aneuploidy generation. Similarly, results suggest that telomere length is not significantly shorter in “preterm at term” infants compared to term born controls, thus providing no evidence that telomere attrition is involved in the pathobiology of the ‘aged phenotype’ observed in preterm infants. Taken together, results from this thesis provide some novel insights into the function of these highly important features of the genome, but also highlight that a great deal remains to be uncovered in the complex molecular mechanisms that contribute to the regulation of telomere length and nuclear distribution.
Supervisor: Griffin, Darren ; Vasu, Vimal Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: QH426 Genetics