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Title: Correlating KSHV strain divergence with cellular genetic markers in Jewish populations
Author: Wilder, Natalie Louise
ISNI:       0000 0001 3568 1772
Awarding Body: University of London
Current Institution: University College London (University of London)
Date of Award: 2003
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The modern-day Ashkenazi and Sephardic Jewish populations were formed during the Diaspora of the Jewish people away from the Near East. Classic Kaposi's sarcoma (KS) has a relatively high incidence in both populations. Kaposi's sarcoma-associated herpesvirus (KSHV) is the cause of KS; variability in the first open reading frame (ORF) K1 has been used to define major subtypes of KSHV with geographic associations. There are two divergent alleles of the gene ORF-K15, predominant (P) and minor (M), which are not associated with ORF-K1 diversity. Total DNA was extracted from archival paraffin-embedded KS biopsy samples from a total of 85 Ashkenazi and 46 Sephardic Jewish KS patients. Using nested PCR and direct DNA sequencing, I have characterised the variability of ORFs K1 and K15 from these Jewish patients and compared it with non-Jewish controls. In the same samples, I have analysed the variability of the coding and control regions of mitochondrial DNA (mtDNA), and of 17 polymorphic markers on the Y chromosome. In this thesis, I describe established and novel KSHV subtypes, and mtDNA and Y chromosome diversity, within the Jewish population. I show that there are significant associations between subtypes A and C of KSHV and the Ashkenazi and Sephardic Jewish populations respectively, and that recent founder effects have caused the evolution of population-specific clades. I also provide evidence of an association between KSHV subtype and mtDNA haplogroup, but a lack of association of KSHV subtype with Y chromosome haplogroup, within both the Ashkenazi and Sephardic Jewish populations, demonstrating the maternal transmission of KSHV in these two communities. This is the largest study of KSHV subtypes to date and the first to combine the study of KSHV diversity with host genetic diversity.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available