Genome sequencing grows faster and more economical

It was exactly 10 years ago, April 14, 2003, that the human genome project reported the first complete sequence of human DNA. Now the U.S. Supreme Court is hearing arguments over whether certain human gene sequences can be patented, a ruling that could affect how science and law intersect for years, if not decades.

The process of mapping the human genome took more than a decade, with a budget of more than $3 billion and the participation of thousands of scientists. The technology has improved greatly, so that it is now possible to sequence a human genome in about eight days, at a cost of around $10,000.

The National Institutes of Health in Bethesda, Md., are pushing researchers to come up with technology that would sequence a person’s entire genome for just $1,000.

Begun in the 1990s, gene sequencing was a slow, laborious and expensive process. Since then, researchers at institutions across the U.S. and U.K. have developed several technologies, and new ones are moving fast from bench to bedside.

One of the newest is nanopore sequencing. This technology is revolutionary because it promises to allow commercial machines to read DNA base sequences directly, offering a faster, cheaper and more convenient way for doctors to use sequencing as routinely as an MRI or blood cell count.

Nanopore sequencing works by passing a single strand of DNA through a hole generally smaller than 1 nanometer in a membrane. The hole can be a biological molecule or punched into a solid surface using an electron beam. As an electric current flows through the pore, each of the four DNA bases disrupts the current in different ways while the machine electronically reads out the sequence like an announcer reading a ticker tape.

Something similar happens in nature all the time. Certain proteins, called ion channels, punch holes in the membranes of cells and selectively allow ions to pass through them. Many biological processes, including infection of cells by some strep bacteria, depend on the ability of ion channels to regulate the flow of ions through cellular membranes.

Existing technologies take five to 10 days just to prepare the DNA for analysis They must chemically amplify and label the DNA so there is enough to read, and they require that the DNA be broken into chunks of less than 100 base pairs, which then have to be analyzed to find identifiable overlaps so they can be pieced together.

The ability to read DNA molecules directly avoids errors that inevitably appear with the processing. It also means reading longer segments of a genome at a time.

Although nanopore sequencing is not yet available commercially, proof of concept has long been established. Oxford Nanopore Technologies announced in February 2012 that by early 2013 it would be selling machines with thousands of nanopores running in parallel, making it possible to sequence a full human genome in 15 minutes for around $1,000.

Waiting until accuracy can be improved to 99 from 96 percent has held up the release of ONT’s doctor’s office machine, but barring unforeseen developments this technology will be a reality in a couple of years.

Richard Brill is a professor of science at Honolulu Community College. His column runs on the first and third Fridays of the month. Email questions and comments to brill@hawaii.edu.