It's hard to imagine how the publication of the complete genome sequence of Jim Watson - assembled with unprecedented speed and cheapness using next-generation sequencing technology - could possibly be bad news for the field of personal genomics. But in an opinion piece accompanying the publication in Nature, genome evolution guru Maynard V. Olson makes that argument:
If Watson took his sequence to a genetic counsellor, there would be little to discuss. The sequence seems to show that he is a carrier for a handful of mutations that might catch a counsellor's interest. But these mutations have no known effects on Watson himself, and would confer risk on offspring only in the highly unlikely event of a marriage between two carriers. None of these mutations is ever likely to be considered an appropriate candidate for screening in the general population — of which, for these purposes, Watson is a representative member.
Recognition of the thin clinical value of this sequence may cause some investors in the new sequencing methods to take pause, given that the major capital investments required to commercialize these technologies have been motivated more by their perceived medical potential than by research applications.
Well, our current ignorance of the functional significance of most genetic variants make a good argument for not getting your genome sequenced right now. But it's not like you need that argument - the best reason for not getting your genome sequenced now is that it's ludicrously expensive (unless you have $350,000 to burn, like Dan Stoicescu).
By the time whole-genome sequencing becomes affordable - in perhaps five years - our understanding of the functional effects of human genetic variation will be dramatically better than today. With each genome that gets sequenced that understanding will grow. And best of all, a genome sequence never becomes obsolete (unlike the SNP chips currently used by personal genomics companies like 23andMe and Navigenics, which will really start to lose their usefulness over the next year or two).
In any case, while we can't predict the functional impact of every single variant in Watson's genome, even our limited current knowledge is enough to reveal some potentially important sites. For instance, Watson carries at least 10 mutations that have previously been associated with severe diseases in humans (in most cases he only carries one copy of a mutation, where two would be required to cause disease). Given that known mutations are only a small fraction of the total sequence changes that could result in severe disease, this suggests that each of us may carry quite a large number of mutations that could potentially result in serious disease in our children, should we be unlucky enough to mate with someone carrying mutations in the same gene.
In addition, the researchers predict that almost 300 of the protein-altering variants in Watson's genome are "probably damaging" to the function of the protein. These types of variants may potentially play a role in susceptibility to disease, although we don't yet know enough to be able to pick them out with any real confidence.
Anyway, it's a start. Olson is certainly correct that we still know far too little about the function of our genome for large-scale sequencing to be used as a population screening tool, but Watson's sequence illustrates that - once our knowledge has improved - there will be plenty of potential functional information to explore in a typical genome.
Update: MassGenomics has a great break-down of the Watson data.
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