CASE 3 YOU, FROM A TO T: YOUR PERSONAL GENOME

One of the high points of modern biology has been the determination of the complete nucleotide sequence of the DNA in a large number of species, including ours. The human genome and many others were sequenced by Sanger sequencing. This technique works well and is still the gold standard for accuracy, but it takes time and is expensive for large genomes like the human genome. There have been many improvements in Sanger sequencing since it was first described, including the use of four-color fluorescent dyes to label the DNA fragments, capillary electrophoresis to separate the fragments, photocells to read the fluorescent signals automatically as the products run off the gel, and highly efficient enzymes. Together, these methods have increased the speed and decreased the cost of DNA sequencing considerably.

However, being able to sequence everyone’s genome, including yours, will require new technologies to bring down the cost further and to increase the speed of sequencing. The first human genome sequence, completed in 2003 at a cost of approximately $2.7 billion, stimulated great interest in large-scale sequencing and the development of devices that increased scale and decreased cost. As in the development of computer hardware, emphasis was on making the sequencing devices smaller while increasing their capacity through automation.

Modern methods of sequencing include the use of fluorescent nucleotides or light-detection devices that reveal the identity of each base as it is added to the growing end of a DNA strand. Another approach passes individual DNA molecules through a pore in a charged membrane; as each nucleotide passes through the pore it is identified by means of the tiny difference in charge that occurs. These miniaturized and automated devices carry out what is often called massively parallel sequencing, which can determine the sequence of hundreds of millions of base pairs in a few hours.

The goal of technology development was captured in the catchphrase “the $1000 genome,” a largely symbolic target indicating a reduction in sequencing cost from about $1 million per megabase to less than $1 per megabase. For all practical purposes, the $1000-genome target has been achieved, but $1000 is still too costly to make genome sequencing a routine diagnostic procedure. The technologies are still evolving and the costs decreasing, and so it is a fair bet that in the coming years your own personal genome can be sequenced quickly and cheaply.