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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Histone modification and the epigenetics of X chromosome inactivation

Spotswood, Hugh Timothy January 2003 (has links)
Dosage compensation serves to equalise the levels of X-linked gene products between males and females. In mammals this occurs through the transcriptional silencing of the majority of the genes on one of the two female X chromosomes. The inactive X chromosome (Xi) differs from its active homologue in a number of ways, including the hypoacetylation of core histones, a common property of genetically inactive chromatin. This study has used Xi to explore the functional significance of hypoacetylation and patterns of histone methylation in silent chromatin. Xi was shown to be depleted for di- and tri-methylated lysine 4 of H3, but retained di-methylated lysine 9 of H3. I have examined the temporal order of these modifications as they become established using an in vitro model system for X inactivation; differentiating female embryonic stem cells. The results showed that the loss of tri-methylated lysine 4 of H3 preceded the loss of its di-methylated equivalent, which occurs during a time period of concurrent core histone deacetylation supporting a functional role to the level of lysine methylation. I have used cases of X;autosome translocation to examine how these modifications relate to late replication and transcriptional silencing. Results show that whilst the spread of X inactivation can occur in the absence of both of these properties, histone modifications are a more reliable indicator of the extent of spread of X inactivation than late replication. To explore mechanisms that drive changes in histone modification I have analysed the distribution of histone deacetylases across a region of defined histone deacetylation. The results showed a ubiquitous distribution that did not correlate with acetylated H3 or H4 suggesting that the global association of the Hdacs might serve to provide a rapid return the basal level of histone acetylation following specific targeting events.
2

Skeletal variation as a possible reflection of relatedness within three medieval British populations

Burrell, C. L. January 2018 (has links)
Nonmetric traits (NMTs) are often used by osteoarchaeologists in the study of human variation. Some NMTs are affected by environmental factors whereas others are genetic in origin. Such genetic variants have long been used to support the hypotheses on the history and divergence of human populations suggesting that some population groups can be genetically distinguished. However, when genetic NMTs occur in higher than expected frequency these can be interpreted as possible indicators of relatedness. This method is applied to a sample of 977 individuals from the Medieval Poulton Chapel, St. Owen’s Church and Norton Priory Collections, U.K. One hundred and twenty-six cranial and postcranial NMTs were examined to determine: 1) the prevalence, 2) whether there are significant differences between the sexes and/or by age category, 3) if there is variation in mechanical and genetic NMT frequency between the three samples and, 4) to explore possible familial relationships through hierarchal cluster analysis and burial spatial distribution. It is thought that family members are often buried near one another, suggesting that individuals sharing similar genetic NMTs would be buried within close proximity to each other. This thesis has revealed the frequency of 126 NMTs for each sample. No significant differences were reported between the sexes at Poulton Chapel whereas significant differences were noted at St. Owen’s Church and Norton Priory, especially for NMTs considered genetic in origin. For all samples, significant differences were found among the age categories. Intra-populational differences were explored between the three samples. The results of these comparisons highlight that 60 NMTs are shared between the Poulton Chapel and Norton Priory Collection, while St. Owen’s Church only shares few traits with both sites. This suggests a probable geographical north-south divide between the three sites. Finally, the hierarchal cluster analysis identified probable familial relationships for the Norton Priory sample. This is supported by the burial spatial distribution and historical documentary evidence. Unfortunately, this analysis was unsuccessful for St. Owen’s Church with limited results for the Poulton Chapel sample. Future research is required to incorporate aDNA analysis to confirm the likelihood of familial links within these sites, supporting the use of certain NMTs is the use of establishing familial relationships.

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