The Quest for the $1,000 Human Genome

The goal of the $1000 Human Genome is almost certainly a little closer with the advent of a new generation of DNA sequencers. Nicholas Wade reports on some of these new developments in the July 18, 2006 issue of the New Yort Times article The Quest for the $1,000 Human Genome.

However, even as we get closer to this NIH-supported goal, the bigger question still remains: What impact will access to the complete genome sequence really have for most people's medical care? The developers of this new technology acknowledge that there is no real demand for this information, at least not yet. They are banking that access to complete genome sequence information will become routinely relevant in healthcare in the next few years. The jury is still out as to what the value of this information will be for most people.

So the question of whether the DNA sequence is likely to be so powerful and predictive that we all should have our genomes sequenced is a relevant one. By itself, the sequence is only potentially related to our health; it yields information about the probabilities of what our health is or will be, but not what our health actually is now or will be in the future. A prime example that illustrates this point are the hereditary cancer syndromes. Even in these families with inherited mutations in "cancer genes", many (if not most) of the individuals who inherit a cancer-predisposing mutation never get cancer. The probablilty that they will eventually develop cancer is higher, to be sure, but they are not sick simply because they inherited this strongly predisposing genetic element. This is even more true for the many less potent genetic elements that we all have that contribute to disease risk. The real story of health lies in the biological processes and interactions that are only partially due to the genome.

Our genes are only half (and sometimes significantly less than half) of our health story, both present and future. The other major players are all the extrinsic factors that make up our environment and the consequences of our behaviors. We are learning more and more about how our genome interacts with the myriad of elements within the genome itself and the almost infinite elements that are extrinsic to the genome. These interactions are more closely related to the health states we experience (both good and bad) than the sequence alone.

Of course, the DNA sequence obviously plays an important role--it is the foundation of our biology. However, the genome functions in an environmental context that regulates its activities at many levels. The technologies to elucidate the physiological consequences of these interactions between genes and environment are developing in parallel with the quest for the affordable genomic sequence. An understanding of how the genome is expressed and how non-genomic factors affect expression will ultimately be more directly relevant to managing the unique and dynamic physiological circumstances that contribute to a person's state of health or a particular disease process. As we close in on the quest for low-cost DNA sequencing, the genome sequence's greatest value may be in what it contributes to our understanding of the interactions between our genome and our environment, and thus, our health.