17The SV study used custom Agilent microarrays to assess the copy number status
of the unannotated sequences by array comparative genomic hybridization (aCGH).
More than 40 % of the novel sequences showed CNV. This map of human SV is
highly consistent with previous high-resolution CNV studies that found a consider-
ably smaller size distribution for CNV regions compared to studies that employed
bacterial artifi cial chromosome (BAC)-based aCGH, and predicts that the current
database of CNV is overstated. The study’s clone-based method enabled mapping
and complete sequencing of many CNV regions, enabling valuable insights into the
mechanisms that mediate human SV.
Role of DNA Sequencing in the Development of Personalized Medicine
Molecular diagnostics and DNA sequencing are among the important basics of
personalized medicine. Role of sequencing in synthetic biology for drug discovery
and development is discussed later in this chapter. Personalized genome sequenc-
ing would become an integral part of personalized medicine as the cost comes
down. Sequencing will also lead to the development of many diagnostic assays that
will contribute to personalized medicine. Simple-to-operate and affordable small
sequencers can be integrated in point-of-care diagnostics for personalized
medicine.
Availability of low-cost genomic sequencing will expand the use of genomic
information in the practice of medicine. Drugs will be targeted better to diseases in
particular patients based on genotype information. Toxicity will be predictable in
most cases prior to drug administration. By the end of the second decade of the
twenty-fi rst century, it is anticipated that the general population will have the oppor-
tunity to carry a chip card, like a credit card, with all the genetic information of the
person coded on it. Such a database can be constructed by taking a blood sample of
the individual, resequencing the functional DNA, and identifying the genetic varia-
tions in functional genes.
Interconnected Genetic and Genomic Patterns in Human Diseases
According to a unifi ed genomic model of human disease, human diseases are caused
by alleles that encompass the full range of variant types, from chromosomal rear-
rangements and CNVs down to the individual SNPs, and these variations span a
broad frequency spectrum, from the very rare to the common. The picture emerging
from analysis of whole-genome sequences, the 1,000 Genomes Project pilot studies,
and targeted genomic sequencing derived from very large sample sizes reveals an
abundance of rare and private variants (Lupski et al. 2011 ). One implication of this
realization is that recent mutation may have a greater infl uence on disease susceptibil-
ity or protection than is conferred by variations that arose in distant ancestors.
Molecular Biological Basis of Personalized Medicine