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Please use this identifier to cite or link to this item: http://hdl.handle.net/10451/1188

Título: Genetic diversity in Mycobacterium tuberculosis: the Beijing/W family
Mycobacterium tuberculosis
Autor: Mestre, Olga Maria Elviro, 1984-
Orientador: Gicquel, Brigitte
Santos, Mário
Palavras-chave: Genética microbiana
Mycobacterium tuberculosis
Teses de Mestrado
Issue Date: 2007
Resumo: The Beijing/W family of Mycobacterium tuberculosis represents a global threat in tuberculosis control. It has been frequently associated with drug resistance and its wide distribution suggests that these strains may have selective advantages over others. On the present study a collection of Beijing/W strains isolated in different countries was analyzed under the genetic markers: Large Sequence Polymorphisms (LSPs) and Single Nucleotide Polymorphisms (SNPs). Through a Multiplex-PCR isolates were tested for the presence or absence of the LSPs, described by a previous study for the Beijing/W family (RD105, RD181, RD150, RD142). The analysis of these regions proved to be very useful for defining and broadly subdivide the Beijing/W family in four groups. Furthermore, it provided a support for selection of representative isolates for the further study of other markers like SNPs in recently identified polymorphic DNA repair, recombination and replication (3R) genes. Selected 3R genes were sequenced for representative Beijing/W isolates to search for variations and comparative analysis with M.tuberculosis H37Rv identified SNPs for all genes. Almost half corresponded to not previously described SNPs and a large proportion seemed specific to Beijing/W strains. SNPs were much more informative than LSPs distinguishing twenty-four groups for which a hypothetic phylogenetic network was constructed. Phylogenetic relations originated by SNPs were found to be congruent with the ones originated by LSPs and also with previous studies on mutT2, muT4 and ogt putative DNA repair genes. Analysis according to geographic origin of isolates suggested that the collection used might be representative of the Beijing/W family. Certain genes were found to be more polymorphic than others with the accumulation of several non-synonymous SNPs (nsSNPs) that may potentially affect the function of the protein. Altered function in proteins involved in such important mechanisms in genome dynamics and stability might be associated with mutator phenotypes strains having high mutation rates in Beijing/W strains, as previously suggested. This might explain their higher adaptability and frequent association with resistance to antibiotics. Overall, this study provided useful information that, although may need to be validated using a larger set of isolates, it could be the start point for several future studies. It may contribute to clarify the role of the Beijing/W family in the tuberculosis pandemic.
Resumo alargado disponível em português
Descrição: Tese de mestrado em Biologia Molecular e Genética apresentada à Universidade de Lisboa através da Faculdade de Ciências, 2007
URI: http://hdl.handle.net/10451/1188
Appears in Collections:FC - Dissertações de Mestrado

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