Wilder, Natalie Louise; (2003) Correlating KSHV strain divergence with cellular genetic markers in Jewish populations. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

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.

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