of the various TB strains each cover roughly 95% of the M. tuberculosis genome. Comparing the DNA sequences in these regions allows the researchers to pinpoint the key differences among them, shedding light on the genetic factors that contribute to TB drug resistance. Strikingly, comparisons of the draft sequences reveal surprisingly few genetic differences among the drug sensitive, MDR and XDR strains: there are only a few dozen small DNA changes. Some of these differences are located in genes known to be involved in TB drug resistance, while others are found in novel genes, whose roles have not been previously investigated. Some of these genes may represent new drug-resistance genes, while others may simply contain random mutations.
That a limited set of genetic differences separates one TB strain from another is important, said James Galagan, the associate director of microbial genome analysis at the Broad Institute. With the analysis of additional XDR strains, it should be feasible to systematically unravel the biological significance of each genetic variation.
These results also lay the groundwork for the development of a rapid diagnostic test for TB, said Murray. Such a test would enable more rapid and accurate diagnoses, and help to prevent the spread of TB especially the most virulent strains.
A significant fraction of the new TB research was accomplished through the use of a powerful new technology for decoding DNA. That approach, based on the principle of single-molecule sequencing, makes it possible to read hundreds of millions of DNA letters simultaneously.
New technologies for sequencing DNA can accelerate the pace of genomic research, particularly for infectious disease, said Bruce Birren, director of the Microbial Sequencing Center at the Broad Institute. It is important that these technologies also be made available to researchers in the field, where they are needed most.
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