Biomedical Engineering Reference
In-Depth Information
motion inside nanopore. In a typical slip event, ssDNA advances one nucleotide
spacing
d
(as clearly seen in Fig.
11.32
).
11.3 Discussion: Beyond Sequencing
The technological progress made from the early chain termination methods [
1
]
of the late 1970s to the present day sequencing methods is truly remarkable. The
ingenuity of the methods presented in this chapter, and of other methods left out for
consideration of length (e.g., [
47
] and [
48
]), have pushed the boundaries of DNA
sequencing in terms of speed, cost and reduced complexity. Indeed, the cost per
finished base pair has decreased seven orders of magnitude in the two decades that
elapsed since onset of the Human Genome Project (1990), when the cost was about
$10 per base [
49
]. Likewise the time required to sequence a human genome
decreased between three to four orders of magnitude. In the words of Fred Sanger,
one of the protagonists of this saga [
50
]: “When we started working on DNA I don't
believe we were thinking about sequencing the entire human genome—perhaps in
our wildest dreams but certainly not within the next 30 years. After all, the human
genome was probably the ultimate goal of all our work.”
Indeed, the
raison d'etre
of all the elegant technologies described earlier in this
chapter is that they will enhance our knowledge of biology in general and of human
biology in particular. We have started to see tremendous progress in that direction. The
ENCyclopedia Of DNA Elements (ENCODE) project, an effort funded by the
National Human Research Institute, has started to produce unforeseen new vistas
into the structural and functional organization of the human genome. The finding of
complex patterns of regulation and transcription together with conservation of non-
coding regions and the abundance of non-coding RNA genes have led some research-
ers to postulate new definitions for the concept of gene [
51
]. Other pioneering effort
designed to bridge the gap between human genetic variation and human health is the
Personal Genome Project (PGP) [
52
]. By recruiting volunteers willing to share both
their genome sequence and their clinical information with the research community,
the PGP will produce a dataset of personal genome sequences that can be evaluated
along with the medical data, to enable the discovery of associations prior to more
rigorous data collection.
Eventually, the hope is that by enabling a phase of intense research in the
association between genomic features and clinical characteristics, fast and cheap
sequencing will enable the era of personalized medicine. The race and efforts to
find the best sequencing technology that we are witnessing is an important part of
the history of the medicine of the future.
Acknowledgments The authors acknowledge useful discussions with members of the IBMDNA-
transistor team: Ali Afzali, Arjang Hassibi, George Walker, Glenn Martyna, Philip Waggoner,
Stanislav Polonsky, Stefan Harrer and Stephen Rossnagel. This work was supported in part by a
grant from the National Institutes of Health (R01-HG05110-01).
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