Biomedical Engineering Reference
In-Depth Information
(At least one genotype databank has executed genotyping of approximately
1,000 individuals at considerable expense and time; however, for experimental
purposes, that databank provides examples of previously executed individual
genotyping at a cost of $0.50-1.00 per sample.) Clearly, an effort to screen a
large number of individuals (say a million) would be slow and very expensive.
In contrast, the methodology described herein is a
selection
for individuals with
a certain genotype rather than a screen. It is correspondingly faster and less ex-
pensive. There is currently no available methodology for selection of specific
genotypes. Many drugs that are quite effective in treating disease are very toxic
to a small portion of the population. Currently, such drugs are removed from the
market to avoid these rare but fatal adverse reactions. Such an approach is very
costly from the standpoint of untreated disease. The removal of drugs from the
marketplace because of rare fatal reactions is very costly in terms of untreated
individuals, as well as the money spent on bringing those drugs to the market in
the first place. Improved methods for identification of individuals at risk for
adverse reactions would eliminate this cost. The capability of screening large
numbers of individuals for a given genotype could also avoid a tremendous po-
tential loss of life in the event of battlefield release of biological weapons or
chemical agents.
As another example of a clinical application, one could construct a Bio-
molecular Database made from the blood samples of people suffering from Alz-
heimer's disease and their families, with the goal of finding genes that may
increase people's risk of contracting the condition. The information tags could be
used to select specific groups of molecules from this database. These molecules,
which come from people with similar clinical symptoms, can then be used to test
a large number of possible Alzheimer's disease genes. Genes that yield promis-
ing results could then be tested on the large number of individual samples from
which the Biomolecular Database was made. The advantage of this approach is
that it allows very efficient use of the limited DNA samples, and it is a good
way to look at lots of different combinations of clinical features.
4.1.2. Large-Scale Gene Expression Profiling Using Biomolecular Databases
One may wish to determine the entire set of genes expressed by a particular
cell type for a population of individuals who suffer debilitating effects due to a
(perhaps unknown) chemical or biological agent. This may allow us to deter-
mine if there is a single or small number of genotypes that characterize suscepti-
bility to that agent, over that population. Gene expression profiling is a labor-
intensive and slow process. The conventional methods used are as follows: (a)
cDNA Hybridization Arrays
, which are 2D arrays of DNA spotted onto a solid
support in an addressable way such that the spatial location of a spot identifies to
the sequence of the DNA bound there. The input cDNA is labeled with a fluo-
