Textbook of Personalized Medicine - Second Edition [2015]

76

Gene Expression Profi ling

The activity of a gene, so called gene “expression” means that its DNA is used as a
blueprint to produce a specifi c protein. The fi rst step of gene expression is transcrip-
tion, the process by which the sequence of DNA bases within a gene is used as a
template to synthesize mRNA. Following transcription, the nascent mRNA is pro-
cessed and transported out of the nucleus and into the cytoplasm of the cell. Once in
the cytoplasm, the mature mRNA is engaged in the last step in gene expression,
translation − the process by which proteins are synthesized. Finally there is post-
translational modifi cation of proteins into mature forms. Each of these steps in gene
expression is subject to precise cellular controls that collectively allow the cell to
respond to changing needs.

Table 2.4 Comparison of proteomic and genomic approaches in personalized medicine

Genotype/haplotype Gene/protein expression

Protein function
studies Metabonomics
Polymorphisms related
to a specifi c level
of enzyme activity

Protein function is

inferred from

expression levels of

mRNA or protein

Direct measurement

of protein

function

Infers level of protein

function from

metabolic profi le

Genotype does not
always correlate
with protein
function

Gene/protein expression

does not always

correlate with

protein expression/

protein function

Direct measurement

of protein

function under

conditions which

mimic drug

exposure

Levels of endogenous

metabolites rather

than exogenous

levels; under

static conditions

Does not account for
polypharmacy,
inducers and
inhibitors

Does not account for

polypharmacy,

inducers and

inhibitors

Accounts for

polypharmacy,

inducers and

inhibitors

Accounts for
polypharmacy,
inducers and
inhibitors
Qualitative Quantitative Quantitative Qualitative
Identifi es
polymorphism
found to correlate
to fast or slow
phenotype

Identifi es increased or

decreased expression

of mRNA or protein

Identifi es responders,

non- responders,

and those that will

experience

toxicity at

standard doses

Identifi es responders,

non- responders,

or those that will

experience

toxicity

Allows semi
categorical
individualization

Lack of correlation,

makes

individualization

inaccurate

Allows accurate

individualization

of therapy to treat

many of those

originally

identifi ed as

non-responders or

at risk for toxicity

Non-responders or

those that will

experience

toxicity are not

treated with

specifi c agent

© Jain PharmaBiotech

2 Molecular Diagnostics in Personalized Medicine