Your Genome is Just a Click Away
Personal genomics has hit the mainstream, but what will it mean for society?
Thu, January 08, 2009
CIO — In the 1997 science fiction thriller Gattaca, Ethan Hawke's character fights to make a life for himself in a world where pervasive genetic testing and manipulation has left the imperfect by the wayside. At the time, it was easy to dismiss the film as a futuristic flight of fancy, not an issue that people would be facing in the next 10 years. After all, the Humane Genome Initiative already had spent years trying to sequence a single man's DNA, and had years left to go.
But, as often happens in technology, the science of genomics followed a "hockey stick" curve. The initial breakthrough of a single sequenced genome required the development of new sequencing techniques, which have drastically reduced the cost and time required.
Currently, commercial services will deliver an entire sequenced genome in less than a month, and there is a concerted effort to reduce that price to under $1,000. Meanwhile, several companies offer consumers the ability to get vast amounts of their genetic data for as little as $400. Personal genomics, so recently science fiction, is now a click away on the Internet. But while this information may offer new insights for individuals into their heritage and physical characteristics, the possibility of a Gattaca-like future suddenly doesn't seem so far-fetched.
The two best-known personal genomic services, 23andMe and deCODEme, both operated in essentially the same manner. After visiting their web site and paying for the testing ($1,000 for deCODEme, $400 for 23andMe), a kit is sent in the mail. The consumer either rubs a stick shaped like a large tongue depressor against the inside of their cheek, or provides a (somewhat voluminous) sample of their saliva. The kit is returned to the company, which then processes the sample.
After a few weeks, the customer's genetic data becomes available on the website. But what he gets is not his complete genetic sequence. Instead, he gains access to as much as a million of their Single Nucleotide Polymorphisms (SNPs). Human DNA is, on the whole, identical from person to person. It is in the small differences brought on by random mutations that all the differences we see between people occur. Many of these differences are a single letter chance in a portion of DNA, a G instead of a C, for example. Fortunately for the companies, these single letter changes are relative easy to detect, and there are now "Snip Chips" that can detect the values of hundreds of thousands of individual SNPs from a single sample at the same time.
"All genetic variation is a result of random mutation," explains Andro Hsu, Science and Policy Liaison for 23andMe. "A lot of SNPs are neutral, in that they don't seem to have any effect on phenotype, which is the physical characteristics of a person. When you have enough of these mutations, and they get spread out to children, then you get a natural set of variation across the population. Over 99.5 percent of the genome is identical between human beings, and it's that last 0.5 percent or so that's different. And SNPs make up a good deal of those differences."
Mining The Genome
Customers can do several things with the data, once available. For example, they can use it to get information about their geographic ancestry, although this is currently a rough estimate at best, broken down into mongoloid, Caucasian and negroid. However, the precision of this data will improve quickly, once more data is available, according to Hsu. He points to a recent study in which Smithkline Glaxo was able to pinpoint the country of origin for European samples with a fairly high degree of precision.
These tests can yield information about paternity and maternity, data that may lead to some awkward realizations. A child has half of his father's SNPs, and half of his mother's. If the child has SNPs that neither the father or mother has, he is either adopted or the father isn't really the father after all. In addition, a male child's Y chromosome is passed down unchanged from the father, and all children get their Mitochondrial DNA (a specialized piece of genetic information in the portion of the cell that produced most of the energy) directly from their mother. So a son or daughter who innocently gets an extended family tested may find skeletons in the closet.
But the use of SNP data that is most controversial is in its relationship to physical characteristics and predilections. Every day, researchers are discovering new associations between SNPs and characteristics such as physical endurance, as well as to potentially life-changing conditions such as diabetes and cancer. It may not be the SNP itself that causes the problem; but because genes tend to stick together through time, SNPs that are close to other defects can serve as markers for the faulty gene itself.
However, the degree to which they may affect an individual may be very weak, explains David Magnus, PhD, Director of the Center for Biomedical Ethics at Stanford. "Most of the traits that we have information about, from say an array that looks at SNPs... in the vast majority of the traits, those are not very predictive. So even if you have a gene for Type 2 diabetes, or that is positively correlated with heart disease, or for being tall, it contributes so little casually, that it doesn't really tell you much about the likelihood of the actually phenotype." This is in contrast to tests such as those for the BRAC1 and BRAC2 genes, which have a large probabilistic impact on the chances of a woman developing breast cancer. "Now [with the new tests] we're talking about things that have so little impact that it's just swamped by any number of other causal factors, including environmental ones."