Segmental Duplications: What's Missing, Misassigned, and Misassembled—and Should We Care?

For many people, the announcement of the release of working draft sequence of the human genome was the climax of more than 15 years of planning and preparation (International Human Genome Sequencing Consortium 2001). Despite the controversy and sensationalism, it was an awesome achievement, culminating in the “genome party of the century”. There was much to celebrate. The majority of genes were identified, mapped to their appropriate location, and await the ascription of phenotypic data.

Among the public, however, there is the impression that the task is a fait accompli. In my case, several family members contacted me after the media blitz to inquire whether I was now out of a job—after all, the Human Genome Project is entering its projected two-year twilight. Indeed, this may be the appropriate time for sequencers and sequence-gazers alike to “jump ship” or at the very least to look beyond the next horizon. The genomic revolution will now launch the proteomics revolution with its promise of tailor-made therapies for the masses. Association studies using SNP data are expected to provide insight into the molecular etiology of complex genetic diseases (Chakravarti 2001). Comparative sequencing of the genome of model organisms such as the mouse and the rat will be used to discover elements critical in the regulation of our own genes and provide an invaluable resource for future mutagenesis studies (Nadeau et al. 2001).

As scientists, we of course know that much work still remains to be done before the final declaration of a finished human genome. We all recognize that gaps remain in the project, and most of the community is committed to rolling up their sleeves and getting on with the final sequence and analysis. Nevertheless, despite this commitment, there remains the impression that gap closure will be akin to “mopping up …