Sunday, February 20, 2011

Mad Science on a Budget: Genome Sequencing

Originally published over at SiMF.

It’s hard to find good help these days. Minions come and go like valence electrons; as soon as you get one of them trained to handle the radioactive waste disposal they end up frying themselves with the Death Ray and you have to start all over again. What a waste of time! Get too many of them together and they start talking about ‘benefits’ and ‘occupational hazards’ and you have to dump the lot of them in the Acid Pit…and who is going to clean up that mess?!?

But imagine if you could screen potential minions for certain…desirable traits before going through the tedious process of hiring, training and eliminating anyone who knows too much? What if you could determine, from just a small sample of genetic material, whether your applicant has the right mix of ability, ignorance and lack of motivation to make the perfect minion? Have a look at their genome and see for yourself!

‘Hold on a tick!’ You may be thinking. ‘Genetic sequencing is a big plorking deal! The Human Genome Project took over ten years and cost a metric butt-ton of cash! I am suspicious of you and your claims.’

And what an informed consumer you are! When the Human Genome Project set out to map the genetics of Homo sapiens sapiens in 1990, the project was expected to take 15 years and cost around $3 billion dollars. They did it in ten (mostly). Sequencing technology continued to advance as the project went on, allowing the researchers to progress at an unanticipated rate. That advancement has continued unabated. The scientists working on the HGP broke the human genome up into chunks of DNA about 150,000 base-pairs long, sequenced the chunks, and then reassembled them into the complete genome. To put this into perspective, the human genome contains 3.3 billion base-pairs. Making things even more difficult, the human genome also contains more segmental duplications than any other mammalian species. These are basically sections of DNA that are nearly identical and are repeated over and over again. Imagine trying to put together a puzzle when you don’t know what the final picture will look like. Then imagine that a sizable chunk of the pieces you do have are identical and are repeated again and again throughout the puzzle. You could be missing pieces, or you may have duplicate pieces, and oh yeah…the pieces are the size of molecules and there are thousands of them. You can see why that might be a wee bit difficult.

But lo, the future is now! We have many advantages that were unheard of in 1990. Next generation, high-throughput sequencing techniques have been developed to produce thousands of sequences at once. And they do it cheaply! The cost of sequencing has plummeted in recent years, dropping from hundreds of millions in 2001 to thousands in 2010. Not only can we generate the puzzle pieces faster and at significantly reduced cost, we now have a picture to look at while we are assembling them in the form of the groundbreaking work performed by the HGP. This moves things right along.

But the HGP didn’t stop there! They have continued to sequence the genomes of other organisms, as well as collect information about the function of the genes identified in the human genome. This information is available to the public online through GenBank. The HapMap project collects differences between individual human genomes. Changes as small as a single base-pair, if observed consistently, could explain why patients react differently to the same medication or why one person is more prone to a certain type of cancer. If you know what to look for, you don’t even need to sequence an entire genome to diagnose a patient…you can just check for these specific sequences.

What? Oh, you don’t care if your minions are prone to diabetes or whether they might have an allergic reaction to your mind-wiping drugs? Well an intelligent customer such as yourself must realize that human traits such as personality, athletic ability and sexual orientation simply do not correspond to specific genes being present or absent. Our genetic make-up is a rather mind-bogglingly big and complex thing. Not only do the genes themselves matter, but when and how they are turned on matters as well, and so does how they are processed and translated into proteins. The proteins themselves, once generated according to the genetic blueprint, can be processed in several different ways and can also be involved in turning other genes on and off. And don’t get me started on the role of the environment! External factors can also affect how genes are expressed, really making it impossible to pin down a single element responsible for just about any one trait. Many human diseases, such as cancer and lupus, are generally the result of several small things going slightly wrong. Rather than having a single smoking gun, you have several different paths that lead you to the same place.

But the power of genome sequencing is undeniable! The potential as a diagnostic tool alone could dramatically affect medicine and how pharmaceuticals are administered. In terms of agriculture, it can revolutionize the way farmers select for specific traits in their crops. It can even make chocolate better! And as the cost of sequencing decreases and more data becomes available, who knows where it will take us? So you see why this is a prime investment opportunity. Why don’t you put away the Death Ray and we can discuss the figures over coffee?

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