79create a diverse array of mRNAs from a single pre-mRNA, a process referred to as
alternative RNA splicing. Splicing is the crucial and tightly regulated step between
gene transcription and protein translation. Alternative splicing could be responsible
for generating up to three times as many proteins as the ~19,000 genes encoded by
the human genome. The ability to analyze RNA splicing events gives a unique
understanding of the sequences that are critical for normal cellular function. The
control of alternative RNA splicing can be deregulated in human disease as a con-
sequence of alterations within signaling cascades, within the spliceosome machin-
ery or within the genes that are spliced.
Alterations in RNA splicing have a signifi cant impact on drug action and can be
exploited to generate pharmacogenomics tools in several ways.
- Alteration of alternative RNA splicing events triggered by drug or chemicals
action constitutes a route through which relevant candidate genes can be selected
for further genotyping because these genes are likely to lie within crucial path-
ways of drug action. - Analyses of RNA splicing might provide a rapid method for detection of poly-
morphisms across the whole gene. - RNA splicing alteration libraries between responders and non-responders would
constitute a discovery tool for pharmacogenomically relevant SNPs.
Gene Expression Analysis on Biopsy Samples
Patient outcomes are frequently known for people whose biopsy samples have been
archived and gene expression analysis of these samples could provide a wealth of
additional information. Analyzing these samples could help scientists determine
why patients did or did not respond to the treatments they were given and provide
greater understanding of which genes are involved in disease mechanisms.
Fortunately, hospitals have collected millions of clinical tissue samples over the past
few decades because they are required to store tumor samples from surgical proce-
dures in case need arises for further testing. However, the standard procedure for
preserving these samples involves immersing the tissue in formalin and embedding
it in paraffi n wax. Formalin-fi xing, paraffi n-embedding (FFPE) preservation pro-
cess destroys, modifi es, or degrades the nucleic acids, specifi cally the DNA and
RNA, in biopsy samples. However reagents are available for extraction of nucleic
acids from FFPE samples to enable gene expression studies.
Profi ling Gene Expression Patterns of White Blood Cells
White blood cells (WBCs) express tens of thousands of genes, whose expression
levels are modifi ed by genetic and external factors. Blood genomic profi les, created
from distinct gene expression patterns of WBCs obtained by microarray
Gene Expression Profi ling