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of equal or greater quality using substantially less sequencing effort. Tools that
facilitate access to phase information will lay the foundation for further advances
throughout genomics and contribute to the development of personalized medicine.
Predicting Drug Response with HapMap
A pharmacogenetic study in cardiovascular disease using a model based on HapMap
revealed that haplotype constituted by allele Gly16 (G) at codon 16 and allele Glu27
(G) at codon 27 genotyped within the beta2AR candidate gene exhibits a different
effect on heart rate curve than the rest of haplotypes (Lin et al. 2005 ). Parents with
the diplotype consisting of two copies of haplotype GG are more sensitive in heart
rate to increasing dosages of dobutamine than those with other haplotypes. This
model provides a powerful tool for elucidating the genetic variants of drug response
and ultimately designing personalized medications based on each patient’s genetic
constitution.
Technologies for SNP Analysis
Technologies used for detection and analysis of SNPs are shown in Table 2.3. These
are described in more detail elsewhere (Jain 2015a ) but some are described briefl y
in the text following Table 2.3. Desirable characteristics of a genotyping technology
are: (1) robust performance and accuracy across a variety of circumstances; (2)
high-throughput performance; and (3) low cost. Sequencing offers the highest
degree of specifi city and selectivity. Restriction fragment length polymorphism
(RFLP), TaqMan assays and DNA microarrays are also frequently used genotyping
methods.
Biochip and Microarray-Based Detection of SNPs
SNP Genotyping by MassARRAY
The starting point for SNPs analysis using the MassARRAY system (SEQUENOM)
is genomic DNA that is easily accessed in a sample of biological material such as
blood. A small amount of blood provides suffi cient material to allow tens of thou-
sands of SNPs to be analyzed in one individual. DNA is prepared by standard pro-
cedures that break open the blood cells, release the DNA and discard other material.
Next, specifi c DNA regions, about 200 base pairs in length, are amplifi ed by enzy-
matic reactions into multiple copies to produce more concentrated samples for eas-
ier analysis. The amplifi ed fragments are then attached by one strand to a solid
surface and the non-immobilized strands are removed by standard denaturation and
washing. The remaining immobilized single strand then serves as a template for
2 Molecular Diagnostics in Personalized Medicine