Biomedical Engineering Reference
In-Depth Information
rescent dye with a unique and readily imaged emission spectrum. After anneal-
ing on this array, the fluorescent cDNA provide a visual readout of the expres-
sion. (b)
SAGE libraries
, prepared by extraction from cDNA of very short tag
sequences that characterize the expressed gene, followed by concatenation of a
number of these tag sequences together for sequencing. Then computer software
(using prior information on the relation between these tags and the original ex-
pressed cDNA) is used to determine which genes are being expressed. Gene
expression profiling can require the development of new cDNA hybridization
arrays, or the construction and sequencing of SAGE libraries. The methods for
parallel analysis of large numbers of samples described here would streamline
this process. In addition, the readout of SAGE data by microarray hybridization
would result in significant savings of time and money as compared to the stan-
dard method of sequencing SAGE libraries. It would enhance our understanding
of both complex disease processes and acute responses to biologic agents.
As another example of a clinical application, one could construct a Bio-
molecular Database made from a large group of healthy people, with the goal of
finding people who are naturally resistant to certain germs, or who respond in
certain ways to prescription drugs. One could study the selection of DNA
strands from this mixture that have a specific sequence change in a specific gene
that is known to change a person's resistance to germs or their response to drugs.
Once these strands are isolated, the information tags would be examined to iden-
tify the people who have that change in their genes. This would be an extremely
useful way to identify people who could have a bad reaction to a drug com-
monly used to treat disease. It could also be very useful in discovering people
who are resistant to naturally occurring diseases or those caused by agents re-
leased during germ warfare.
4.1.3. Streamlining Identification of Susceptibility Genes
In terms of high-throughput screening of candidate genes to optimize ge-
netic association analysis for complex diseases, consider the problem of ge-
nomic characterization of those individuals who first were infected by a
biological agent, and then died. The death may often have been due to complica-
tions involving additional "complex" diseases, such as heart disease. Hence,
mortality resulting from a chemical or biological agent attack may often have
been due to complications involving a preexisting disease such as heart disease.
Mortality can thus often only be predicted by considering both the individual's
susceptibility to that agent, as well as that to various preexisting "complex" dis-
eases. For many "complex" diseases, susceptibility often depends on a number
of single-nucleotide polymorphisms (SNPs) in the human genome. Research
into the genetic causes of complex disease is currently very expensive, and pro-
gress is slow, and complex diseases are quite common, affecting large propor-
