If I wish to have sequenced only exons of my coding genes (exome) for 1K$ price, how that be technically possible?? With sequencing-by-separation (e.g. Sanger) approach that is possible now, but for a much bigger price.

I doubt we will be able to sequence a genome for only 1,000 dollars for a while yet. The sooner the better though.

Geez, you guys are such pessimists! I’m sure George and the companies he advises have technologies under development that will blow our genomic socks off.

[...] finish this edition with a quote from George Church featured by Eye on DNA: If you have cancer predisposition, you can get early diagnosis. You can get a mastectomy so you [...]

[...] can be learned about the different neurological wiring of an autistic person. And yesterday’s Eye on DNA quotes Dr. George Church, professor of genetics, Harvard University and founder of the Personal [...]

[...] his personalized genetics summaries. In a recent one he points to a quote from George Church (via Eye on DNA) If you have cancer predisposition, you can get early diagnosis. You can get a mastectomy so you [...]

Ramunas (and others) - a few groups have developed methods to amplify a large set of specific sequences in one large multiplex reaction. One can do this for, say, all exons, and then use cheap next-generation sequencing methods (rather than Sanger) to determine the sequences in that amplified set - i.e. sequence just the “exome”. This is currently feasible for ~$1k.

If you are interested in the technical side (and have access), here is a reference for the Church group’s version of the technology:

Porreca GJ et al. Multiplex amplification of large sets of human exons. Nat Methods. 2007 Nov;4(11):931-6.

A new generation of technologies is poised to reduce DNA sequencing costs by several orders of magnitude. But our ability to fully leverage the power of these technologies is crippled by the absence of suitable ‘front-end’ methods for isolating complex subsets of a mammalian genome at a scale that matches the throughput at which these platforms will routinely operate. We show that targeting oligonucleotides released from programmable microarrays can be used to capture and amplify approximately 10,000 human exons in a single multiplex reaction. Additionally, we show integration of this protocol with ultra-high-throughput sequencing for targeted variation discovery. Although the multiplex capture reaction is highly specific, we found that nonuniform capture is a key issue that will need to be resolved by additional optimization. We anticipate that highly multiplexed methods for targeted amplification will enable the comprehensive resequencing of human exons at a fraction of the cost of whole-genome resequencing.

This is exciting and scary at the same time. I read the disclaimer in Dr. Church’s research subject recruitment document (does this disturb anyone else?):

Volunteers should be aware of the ways in which knowledge of their genome and phenotype might be used against them. For example, in principle, anyone with sufficient knowledge could take a volunteer’s genome and/or open medical records and use them to (1) infer paternity or other features of the volunteer’s genealogy, (2) claim statistical evidence that could affect employment or insurance for the volunteer, (3) claim relatedness of the volunteer to infamous villains, (4) make synthetic DNA corresponding to the volunteer and plant it at a crime scene, (5) revelation of disease lacking a current cure.

Thank you Jack for this reference - well, it’s really seems possible… Only some optimization need to be done. When it came to a clinic, a dramatic price reduction should come. But I think the cost of interpretation should increase (as a service), at least in the beginning.