The National Human Genome Research Institute (NHGRI) portion of the US National Institutes of Health (NIH) has awarded a Centers of Excellence in Genomic Science (CEGS) to a team at Harvard Medical School to develop cheaper and faster DNA sequencing technologies.

At Harvard, a team led by George Church, Ph.D., will address the biomedical research community's need for better and more cost-effective technologies for imaging biological systems at the level of DNA molecules (genomes) and RNA molecules (transcriptomes). The center will receive $2 million annually in CEGS funding for five years.

Specifically, the Harvard center plans to further develop polymerase colony sequencing technologies for studying sequence variation in biological systems. In this highly parallel method of nucleic acid analysis, a sample of DNA is dispersed as many short fragments in a polyacrylamide gel affixed to a microscope slide. Researchers then add an enzyme called DNA polymerase, which copies each DNA fragment repeatedly, forming tiny, localized sets of identical fragments. These sets of fragments are embedded in the gel in a manner reminiscent of bacterial colonies, which has prompted scientists to refer to them as "polonies."

Next, the polonies are exposed sequentially to free DNA bases tagged with fluorescent markers in the presence of a different enzyme, and the incorporation of those bases into the polonies is monitored with a scanning machine. This produces a read-out of the DNA sequence from each polony. A computer program then assembles the DNA sequences from the individual polonies into an order that reflects the complete sequence of the original DNA sample. The ordering process is accomplished by aligning the sequences of the individual polonies with a reference DNA sequence, such as the sequence produced by the Human Genome Project. In addition to its application in DNA sequencing, polony technology can be used to study the transcriptome (RNA content) of cells and to determine differences in genome sequence between different individuals (genotypes and haplotypes).

The technology developed by Church's team currently can read a slide with 10 million polonies in about 20 minutes, making it one of the swiftest DNA sequencing methods now available. With the further development planned at the center, the technology has the potential to lead to quicker, more cost-effective ways of sequencing individual genomes for use in research or clinical settings. Producing a high-quality draft of a mammalian-sized genome currently costs about $20 million, but NHGRI's aim is to dramatically reduce that cost to $1,000 over the next 10 years.

"In order to reach that ambitious goal, we will need to develop a completely integrated system that requires very small volumes and utilizes very inexpensive instruments. Ideally, the system would cost no more than a good desktop computer," said Dr. Church.

Cheap fast DNA sequencing will allow individuals to have their DNA sequenced. That ability will usher in a new era where the knowledge of a given person's DNA sequences will lead to many changes. Among the practices that will become commonplace once personal DNA sequencing becomes cheap:

• Nutritional genomics. Each individual will be given dietary advice customized to their genetic predispositions.
• Pharmacogenomics. One aspects of this will be personalized drug selection to avoid adverse reactions and to enhance therapeutic effects.
• Development of drugs aimed at subsets of the general population who will most benefit from particular mechanisms of drug action.
• Identification of individuals who are especially susceptible to particular environmental toxins so they know to avoid such toxins.
• Identification of all genetic variations that influence intelligence and personality. This will lead initially to changing mating rituals as people pursue potential mates with most heavily desired genetic variations.
• As part of changes in mating strategies people will surreptitiously steal tissue samples from each other in order to sequence each other's DNA. Genetic privacy will become impossible to protect.
• Many women will opt to use sperm bank sperm to get their ideal male genetic donation.