Feng, Xiaodong_ Xie, Hong-Guang - Applying pharmacogenomics in therapeutics-CRC Press (2016)

Essential Pharmacogenomic Biomarkers in Clinical Practice
55
Resistant
Clinical treatment
Sensitive
T
T
G
GENE 1
A
GENE 2
A
C
GENE 3
C
G
G
GENE 1
A
GENE 2
T
G
GENE 3
T
T
G
GENE 1
G
GENE 2
T
C
GENE 3
C
T
G
GENE 1
G
GENE 2
T
C
GENE 3
FIGURE 3.2 Overview of pharmacogenomic discovery. For the aim of precision and
personalized medicine, pharmacogenomic biomarkers can be used to separate patients
based on a particular therapeutic phenotype (resistant or sensitive to a drug). Various highthroughput
technologies, such as microarray- and sequencing-based platforms, are now
available to profile molecular targets to be tested for genes and/or genomic loci associated
with a therapeutic phenotype.
extensive genetic variations among individuals from global populations. For example,
the 1000 Genomes Project (phase I integrated release) reported >17 million SNPs
by sequencing 1092 individuals from 11 global populations from Asia, Africa, the
Americas, and Europe. 15 The majority (approximately 90%) of genetic variations is
found within major global populations (Asians, Europeans, and Africans), and only
an additional 5–15% of variations is found between any two populations. 16 In contrast
to other global populations, African individuals typically have a higher level of
genetic diversity than non-African populations. 17,18
In particular, it has been estimated that a 99.9% genetic identity exists between
any two randomly chosen individuals. The 0.1% differences in an individual’s genetic
make-up (corresponding to approximately 3 million base-pair differences between
any two randomly picked individuals) likely play an important role in defining complex
traits and phenotypes, such as adult height, skin color, body mass index, as well as
risks for common diseases. 19 Importantly, gene expression, an intermediate phenotype