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Home Letters Whole-Genome Sequencing (WGS) and the Changing Landscape of Bacterial Genetics
Whole-Genome Sequencing (WGS) and the Changing Landscape of Bacterial Genetics Print E-mail

 

Shotgun sequencing of Haemophilus influenzae in 1995 is traditionally considered to be the dawn of the modern era of whole genome sequencing (WGS). In 2004, the introduction of pyrosequencing based (454/Roche) massively parallel sequencing (MPS) brought about the second wave of advances in WGS. The advent of NextGen sequencing technologies is making great impacts in many areas of research and is already changing the landscape of bacterial genetics as well. Genetic mapping of mutations in bacteria is an arduous process taking anywhere from months to years. Because of the availability of rapid and low-cost WGS technologies, mapping mutations directly without resorting to traditional genetic approaches is now feasible even in bacteria for which genetic mapping systems are not available.

Several articles have already been published demonstrating the utility of the WGS approach for mutation mapping in bacteria and other organisms (e.g., B. M. Davis and M. K. Waldor, Nucleic Acids Res. 37:5757-5767, 2009). Our own study using pyrosequencing technology has identified a number of causal variations leading to specific phenotypic changes such as phage resistance and ciprofloxacin resistance in Bacillus anthracis (unpublished). For the past few years, comparative genome hybridization (CGH)-based whole-genome resequencing had been the preferred approach for mapping causal variations of specific phenotypes (T. J. Albert et al, Nature Methods 2:951-953, 2005). Current paradigm shift from CGH to WGS for variation detection is largely driven by the low cost (from few thousand dollars to ~$10,000 for bacterial genomes), the volume of sequence data (450 Mb to 60Gb) and the rapidity (24 hours to a week) with which currently available second-generation sequencers can generate draft genome sequences of adequate breadth and depth of coverage. The cost of draft sequencing is likely to decrease considerably in the next few years. Gone are the days of conventional genetic and physical mapping of mutations, and we predict that in the not-too-distant future, WGS will be a routine microbial lab procedure for mapping mutations and the ultra-deep sequencing capability of NextGen sequencers will be exploited for the routine microbial analyses of clinical specimens and viral populations in patients to identify quasispecies.

Shanmuga Sozhamannan
Kimberly Bishop-Lilly
Naval Medical Research Center,
Rockville, Md.

Mathumathi Rajavel
Medical Technology Program
School of Computer, Mathematical and Natural Sciences
Morgan State University
Baltimore, Md.