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Using genomics to understand the origin and dispersion of multidrug and extensi...

Perdigão, João; Gomes, Pedro; Miranda, Anabela; Maltez, Fernando; Machado, Diana; Silva, Carla; Phelan, Jody E.; Brum, Laura; Campino, Susana

Portugal is a low incidence country for tuberculosis (TB) disease. Now figuring among TB low incidence countries, it has since the 1990s reported multidrug resistant and extensively drug resistant (XDR) TB cases, driven predominantly by two strain-types: Lisboa3 and Q1. This study describes the largest characterization of the evolutionary trajectory of M/XDR-TB strains in Portugal, spanning a time-period of two...


Genome-wide analysis of Mycobacterium tuberculosis polymorphisms reveals lineag...

Oppong, Yaa E. A.; Phelan, Jody; Perdigao, Joao; Machado, Diana; Miranda, Anabela; Portugal, Isabel; Viveiros, Miguel; Clark, Taane G.

Background: Continuing evolution of the Mycobacterium tuberculosis (Mtb) complex genomes associated with resistance to anti-tuberculosis drugs is threatening tuberculosis disease control efforts. Both multi- and extensively drug resistant Mtb (MDR and XDR, respectively) are increasing in prevalence, but the full set of Mtb genes involved are not known. There is a need for increased sensitivity of genome-wide ap...


Recombination in pe/ppe genes contributes to genetic variation in Mycobacterium...

Phelan, Jody E.; Coll, Francesc; Bergval, Indra; Anthony, Richard M.; Warren, Rob; Sampson, Samantha L.; Gey van Pittius, Nicolaas C.; Glynn, Judith R.

Background: Approximately 10 % of the Mycobacterium tuberculosis genome is made up of two families of genes that are poorly characterized due to their high GC content and highly repetitive nature. The PE and PPE families are typified by their highly conserved N-terminal domains that incorporate proline-glutamate (PE) and proline-proline-glutamate (PPE) signature motifs. They are hypothesised to be important vir...


Rapid determination of anti-tuberculosis drug resistance from whole-genome sequ...

Coll, Francesc; McNerney, Ruth; Preston, Mark D.; Guerra-Assunção, José Afonso; Warry, Andrew; Hill-Cawthorne, Grant; Mallard, Kim; Nair, Mridul

PMID: 26019726 WOS:000355073700001; Mycobacterium tuberculosis drug resistance (DR) challenges effective tuberculosis disease control. Current molecular tests examine limited numbers of mutations, and although whole genome sequencing approaches could fully characterise DR, data complexity has restricted their clinical application. A library (1,325 mutations) predictive of DR for 15 anti-tuberculosis drugs was c...


Rapid determination of antituberculosis drug resistance from wholegenome sequen...

Coll, Francesc; McNerney, Ruth; Preston, Mark D.; Guerra-Assunção, José Afonso; Warry, Andrew; Hill-Cawthorne, Grant; Mallard, Kim; Nair, Mridul

Mycobacterium tuberculosis drug resistance (DR) challenges effective tuberculosis disease control. Current molecular tests examine limited numbers of mutations, and although whole genome sequencing approaches could fully characterise DR, data complexity has restricted their clinical application. A library (1,325 mutations) predictive of DR for 15 anti-tuberculosis drugs was compiled and validated for 11 of them...


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