Biomedical Engineering Reference
In-Depth Information
Chapter 1
Sanger Sequencing Principles, History,
and Landmarks
1.1
Historical Overview
The fi rst DNA sequencing (1968) was performed 15 years after the discovery of the
double helix (1953) (Hutchison
2007
). However, the chemical method of Maxam
and Gilbert and the dideoxy method of Sanger began in the mid-1970s (Fig.
1.1
).
The profound insights into genetic organization were shown by Nicklen and Coulson
with the fi rst complete DNA sequence of phage
X174. As sequencing output
improved, larger molecules greater than 200 kb (human cytomegalovirus) were
sequenced and computational analysis and bioinformatics was born. Sequencing
efforts reached new heights with the initiation of the US Human Genome Project
culminating in the fi rst “sequencing factory” by 1992 (Hutchison
2007
). With this
effort came the sequencing of the fi rst bacterial genome, by 1995, and other small
eubacterial, archaebacterial, and eukaryotic genomes soon thereafter. Published in
2001, the working draft of the human genome sequence was the result of the com-
petition between the public Human Genome Project and Celera Genomics (Fig.
1.1
).
The new “massively parallel” sequencing methods (Chap.
2
) are greatly increasing
sequencing capacity, but further innovations are needed to achieve the “thousand
dollar genome” that many feel is the prerequisite to personalized genomic medicine
(Fig.
1.1
). These advances will also allow new approaches to a variety of problems
in biology, evolution, and the environment.
In this chapter we describe the principles and history of Sanger sequencing that
led to the creation of sequencing centers that were eventually responsible for
sequencing the human genome, the dawn of genomic medicine. In addition, we
briefl y introduce the principle and platforms available for NGS and conclude by
refl ecting on the dream of achieving the $1,000 genome through computational sup-
port. Moreover, in Part I of this topic (Chaps.
1
,
2
, and
3
), we will discuss in detail
the principles of next-generation-sequencing (NGS; Chap.
2
)
and enrichment tech-
nologies (Chap.
3
)
. In Part II, we will include the clinical applications of NGS in
medical genetics. Specifi cally, a cursory view of the fi eld will be covered (Chap.
4
)
,
ϕ
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