The recent emergence of next-generation sequencing technology has opened up the possibility to sequence billions of basepairs very quickly. Today, three commercial next-generation DNA sequencing systems are available: the (454) GS FLX Genome Analyzer marketed by Roche Applied Sciences, Illumina's Solexa 1G sequencer, and most recently Applied Biosystem's SOLiD system. In the next few years we expect third-generation sequencing technology, so-called single molecule sequencing, to appear on the market.
Next-generation sequencing offers rapid ways for the genome-wide detection of single nucleotide polymorphisms and structural variation, mRNA profiling, and identification of transcription factor binding sites. It is also being applied in medical genomics to resequence loci that are associated with disease and it will probably be implemented in diagnostics for the quick and thorough genotyping of patients’ DNA.
We are currently setting up an infrastructure for massive parallel sequencing using Applied Biosystems SOLiD system (sequencing by oligo ligation detection). The SOLiD sequencer uses a unique protocol for sequencing by ligation (see Figure 1). In this process, single DNA molecules are clonally amplified on beads, which are deposited on a glass slide. The sequence of the DNA on the beads is determined by ligation of fluorescently labelled octameric DNA probes using the clonal DNA on the beads as a template. The di-base encoding strategy makes the SOLiD system unique among the current next-generation sequencing platforms and is fundamental to its unmatched accuracy.
With the promise of even more powerful sequencing machines in the near future, including sophisticated bioinformatic tools to analyze the sequencing information, the low cost resequencing of individual genomes is within reach. Personal genomic information can be used to select the most effective drug to treat a patient, while minimizing the risk of potential side effects. Furthermore, complete genome information of cancer tissue, which is characterized by various types of changes to its DNA, may provide valuable information about its molecular and cellular characteristics. Finally, a personal genotype catalogue (genenpaspoort) may reveal an individual’s risk for common diseases, such as hypertension or diabetes. This information may help people to start preventive treatment, have surgery or adopt a different lifestyle that counteracts the increased risk for disease. Adjusting medical treatment to a person’s individual needs may improve the efficacy of the drugs prescribed and significantly limit future healthcare costs.
Sequencing complete genomes of individual patients is associated with several ethical issues. Who will become the owner of a person’s genetic information? Will we allow people to be discriminated against, e.g. by health insurers, based on their genetic passport?
If you would like to be involved in the development and application of next-generation sequencing technology and personal genomics approaches to future medicine, please contact
Dr. Wigard Kloosterman or
Prof. Edwin Cuppen.
Figure 1. Overview of the SOLiD-sequencing-by-ligation approach.
