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Title: The role of IS6110 insertion element in the evolution of Mycobacterium tuberculosis
Author: Bidaki, Majid Zare
ISNI:       0000 0004 2672 5173
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 2009
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The role of the transposable insertion sequence IS6110 was studied in the evolution of Mycobacterium tuberculosis in 202 isolates from 40 countries. The isolates were analyzed by IS6110 insertion site mapping, spoligotyping, IS6110 RFLP fingerprints and in silico comparisons. Different IS6110 insertion sites exhibited a wide range of variation in the presence or absence of IS6110 in isolates varying between sites with only one isolate identified with the insertion, singletons, to sites where many isolates harboured an IS6110 insertion, common insertions.  95% of isolates were split into ten IS6110 cluster groups or lineages (ICG-1 to 8, ICG-a and ICG-b) based on their common IS6110 insertion site patterns.  No M. tuberculosis isolates were found which were intermediate between ICG cluster groups.  A non-random association of IS6110 alleles over loci and also a high correlation between the common IS6110 cluster groups and spoligotype families suggested that common IS6110 insertions are predominantly the result of unique evolutionary event polymorphisms and they are therefore robust and valuable markers for phylogenetic and evolutionary studies of M. tuberculosis. 14 IS6110-assocaited deletions, including nine new regions of deletion were detected in the studied isolates.  Phylogenetic analysis of these genomic deletions demonstrated that they can also be used to classify the majority of MTB lineages including ICG-1/Beijing, ICG-3/CAS, ICG-5/a part of T, ICG-4/S and a major part of the ICG-6/LAM lineage. Published literature and DNA sequence databases were used to establish a global IS6110 database comprising of 524 different IS6110 insertion sites across the genome and this database was used to study the role of IS6110 in the fitness of M. tuberculosis.  The distribution of these sites showed a significant bias into intergenic regions, non-essential genes, multi-copy genes, other insertion elements and genomic repeat regions.  Common IS6110 insertions may well have played an important role in the evolution of M. tuberculosis.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Microbiology ; Mycobacterium tuberculosis ; Tuberculosis