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Telomere Length and Distribution in Three Developmental Stages

Turner, Kara Jane (2014) Telomere Length and Distribution in Three Developmental Stages. Doctor of Philosophy (PhD) thesis, University of Kent,. (KAR id:47463)

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Abstract

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:

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

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.

Item Type: Thesis (Doctor of Philosophy (PhD))
Thesis advisor: Griffin, Darren K.
Thesis advisor: Vasu, Vimal
Uncontrolled keywords: Telomere, infertility, preterm birth
Subjects: Q Science > QH Natural history > QH426 Genetics
Divisions: Faculties > Sciences > School of Biosciences
Depositing User: K.J. Turner
Date Deposited: 28 Feb 2015 01:00 UTC
Last Modified: 23 Jan 2020 04:09 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/47463 (The current URI for this page, for reference purposes)
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