The $1000 genome

The Postdoc Perspective was a blog for the Physics and Astronomy Department at McMaster University in Canada that I kept while I was a postdoctoral researcher. Many of the topics were talks presented at the McMaster Origins Institute seminar series.  

My Dad has high blood pressure and my Mum had to receive treated breast cancer but what does this say about my future health? It is possible I have a predisposition to both these conditions but I may also never develop either. The difference comes down to what combination of genes I have inherited and for me to know for sure, my genome would have to be mapped.

The U.S. Department of Energy Human Genome Project Information Web site estimates it would take "about 9.5 years to read out loud (without stopping) the more than three billion pairs of bases in one person's genome sequence"[*]. It therefore unlikely to surprise you that the mapping of your personal genome does not come cheaply. Currently, you're looking at around $50,000 - $100,000 which only seems affordable in light of the fact the first genome to be mapped in 2003 cost $3,000,000,000.

Now, however, a new technique for gene mapping is being developed that could bring the cost down to under $1000. This would allow personal genomics to become available for predictive medicine. As our Origins' colloquium speaker, Professor David Deamer from the University of California Santa Cruz, suggested, you could imagine having your own genome stored on a thumb drive to take with you when you visited your doctor.

Professor Deamer first conceived the idea for the $1000 genome over twenty years ago. He postulated that if it were possible to create a hole in a biological cell that was sufficiently narrow that only a single strand of DNA could pass through it, then the DNA components ("nucleotides") could be analysed and recorded as they were dragged through. Combined, this pattern of DNA components make up your genes[**]. The question was what could be used to create such a tiny channel?

The answer to this did not emerge until ten years later and turned out to be a toxin called alpha-hemolysin. As its description suggests, hemolysin is not normally remotely desirable and is released during staph infections where it burrows into red blood cells and makes them explode (not good). In this case, however, its burrowing ability is exactly what Professor Deamer's team were looking for.

Alpha-hemolysin adheres to a cell's surface and makes a hole through the cell's structure known as a 'nano pore'. When a small voltage is applied, charged particles pass through the cell to create a tiny, but measurable, electric current. When a DNA strand attempts to pass through the hole, it can only just fit. This means it temporarily blocks the channel while it is squeezing through, causing the electric current to drop. The amount the current falls by turns out to be determined by which nucleotide is currently in the way. By measuring the change in current, the genome can be mapped.

The familiar picture of DNA is not of a single strand, but of the double helix. Tied up in this manner, the DNA cannot fit through the nano pore. Instead, it enters the broader, top part of the channel and get struck. From this position, it becomes unzipped until it can finally pass through the hole and out of the cell. The very exact size of the hole is important, since to record the genome accurately, only one nucleotide at a time must exit the cell.

Genome mapping using this technique is not yet available, but Oxford Nanopore Technologies have plans to produce a commercial device using this process. That being the case, there is only really one question left:

Are you ready to know what you really are?

[*] In case anyone is really curious, this figure is calculated by assuming a reading rate of 10 bases per second, equaling 600 bases/minute, 36,000 bases/hour, 864,000 bases/day, 315,360,000  bases/year. So there.

[**] Nucleotides make up DNA strands and stretches of DNA strands make up genes (in case anyone else was confused about the order of the extremely small).