Biomedical Engineering Reference
In-Depth Information
tions of the population. Delays in understanding the genetic basis of these dis-
eases slow the development of improved treatments at a significant financial and
human cost. In the last 2 to 3 years, there have been several large-scale efforts to
identify single-nucleotide polymorphisms in the human genome. The SNP con-
sortium, a non-profit foundation composed of the Wellcome Trust and eleven
pharmaceutical and technological companies, has agreed to deposit all SNPs
they discover to public databases such as dbSNP, the SNP database maintained
by the National Center for Biotechnology Information (NCBI). The number of
entries in this database has increased from several thousand to over two million
within the last 3 years. This sudden increase in the number of polymorphic
markers has completely overwhelmed current methods for SNP genotyping and
high-throughput screening. It has also become apparent that the incidence of
single-nucleotide polymorphisms varies widely from one region of the genome
to another, and large numbers of SNPs must be screened to analyze each candi-
date gene. Even with unlimited funds and the capacity for genotyping, serious
challenges to the family-based association screening would remain, because the
individual screening of a large number of SNPs would quickly exhaust the
amount of DNA that can be easily obtained from a single individual. This prob-
lem is compounded by the sample cost of preparing pools of DNA from multiple
individuals by simple mixing: once samples are mixed they cannot be separated
again, and leftover, pooled DNA is wasted. Indexing of a Biomolecular Data-
base can be of significant assistance in this regard. Large numbers of different
groups of individuals can be selected from the Biomolecular Database by logical
queries on the information tags. These pools can be used for allelic frequency
determinations, and any remaining DNA can be added back to the remaining
database.
As another example of a clinical application, one could use Biomolecular
Databases to help discover what genes are turned on in a specific tissue of the
body. Genes that are needed in the brain may not be expressed in the muscles,
and genes needed in the muscles may not be needed in the liver. For this reason,
measuring what genes are turned on in a specific tissue can help us understand
what the possible functions of those genes might be. Biomolecular Databases
would provide increased efficiency for these approaches.
4.2. Further Applications
The applications described above could be of critical value to the United
States in the event of a terrorist release of a biological or chemical agent, as
in the following brief scenario. A biological agent is released by a terrorist
group in an American city or another populated area. The city is evacuated,
but it becomes necessary to traverse a potentially contaminated area, or to re-
visit a known contaminated area. Clearly, any personnel sent into this area,
