The NG Question of the Year

The journal Nature Genetics is running a'Question of the Year' website, which they will update monthly, here. This year they are asking geneticists what they would do if the capacity to sequence the equivalent of a full human genome for $1,000 were available today. Here are two of the first round of responses to this question:

Francis S. Collins (National Human Genome Research Institute): where to begin?
The real question is, "What wouldn’t we do?" At the National Human Genome Research Institute, we'd be like kids in a candy shop—there are so many exciting possibilities from which to choose. Bearing in mind our mission of using genomic research to improve human health, we'd probably take most of our current annual spending on DNA sequencing, about $120 million, and devote it to sequencing 100,000 human samples for $100 million. About 75,000 of those samples would come from obtaining the complete genome sequences of 2,500 affected individuals for each of 30 common, complex diseases, such as asthma, arthritis, diabetes, various types of cancer, heart disease, stroke, Alzheimer’s disease and depression. This would enable us to systematically find both the common and the rare genetic variations that contribute to the risk of developing these diseases. The remaining genomes to be sequenced would be those of 25,000 people who have made it to the age of 100 in relatively good health and retaining the capacity for independent function. The aim of that endeavor would be to see what's special about the genomes of healthy centenarians, and then to use that information to explore the genetics of good health and longevity in all humans.

George Church (Harvard Medical School): the Personal Exome Project
If the equivalent of a complete human genome could be sequenced for only $1,000, then we should sequence all exons (also known as the 'exome') for $10—a bargain that the world could not afford to ignore ($60 billion for 6 billion people). The exome is the 1% of the genome most easily interpreted and most likely to cause noticeable phenotypes. Even if we never get to $10, it is likely that the exome is already, in 2006, 'affordable' for the global middle class: $4,000 (e.g., using polonies)—an amount recoverable over a lifetime at $50/year in healthcare savings. Association studies based on 'pathway sequences' for a million early adopters could benefit the rest of us in a way that is out of reach with current 'common variant' and/or 'linkage disequilibrium' methods. Pathway sequence studies look for associations between a disease and any 'obviously deleterious alleles' (e.g., protein-truncating alleles or changes in highly conserved amino acids) anywhere in the pathways potentially relevant to the disease (which can include dozens of loci unlinked genetically but well-linked conceptually). This would crank up the already high motivation to work out the social components of sharing integrated genome and phenome data with trusted researchers—and at a million, the statistics would be awesome. This would permit broadening the number of hypotheses simultaneously testable (i.e., combinations of alleles and environments). This might transform personal genomic medicine from a luxury to a birthright.

For an examination of some of the potential ethical and legal implications of a $1000 Genome, see this In-Focus article by John A. Robertson in AJOB, August 2003.

Cheers,
Colin