Comments on "White Paper #4: The Future of Genome Sequencing"

Several issues that should be considered in future genome sequencing plans:
1. What should be proposed/done is to a significant degree dependent on how fast and inexpensive sequencing becomes, and when such improvement would occur (admittedly something that can only be estimated).
Ideas that are of high merit but are currently impractical and/or too expensive now may be feasible when sequence technology improves further. A list of such projects could be put together so that they are ready to go once the technology is ready.

2. Extreme phenotypes: Assumming whole genome sequencing becomes much more practical (faster and cheaper), consideration should be given to looking at the genomes of extreme phenotypes. The idea of looking at "mutations" has been among the earliest strategies in genetics. The application of the strategy could be extended to humans as well as other organisms. By allowing the comparison of whole genomes (extreme vs. normals), the strategy holds the promise of identifying key genomic changes that underlie the extreme phenotypes.

3.Dynamic, complex, unfinished genomic regions:
These areas still lag behind in sequencing coverage/completeness and unless new sequencing methods will do a better job of accurately covering these regions they will remain excluded from most genomic comparisons. This if particularly damaging in that recent work is finding that such regions are key players in human diseases and evolutionary adaptation...i.e. among the most interesting in the genome. The nature of how, when and why these regions change is a critical, yet poorly addressed question. New sequencing approaches should keep these regions in mind and some support should be given to pursue such questions.

4.Duplicated regions:
Will newer sequencing methods accurately detect and score highly duplicated regions? These are among the most active and biologically interesting regions of the genome, yet they are often misassembled by current sequencing approaches. Will newer sequencing approaches be able to correctly identify and assemble such sequences, and if not, are there other approaches that will be needed?

(136) Thursday, January 29, 2009 11:15 AM