Biomedical Engineering Reference
In-Depth Information
the identifi cation of previously undiscovered proteins that will have potential therapeutic applica-
tion, i.e. the process should help identify new potential biopharmaceuticals. The greatest pharma-
ceutical impact of sequence data, however, will almost certainly be the identifi cation of numerous
additional drug targets. It has been estimated that all drugs currently on the market target one (or
more) of a maximum of 500 targets. The majority of such targets are proteins (mainly enzymes,
hormones, ion channels and nuclear receptors). Hidden in the human genome sequence data is
believed to be anywhere between 3000 and 10 000 new protein-based drug targets. Additionally,
present in the sequence data of many human pathogens is sequence data of hundreds, perhaps
thousands, of pathogen proteins that could serve as drug targets against those pathogens (e.g. gene
products essential for pathogen viability or infectivity).
While genome sequence data undoubtedly harbours new drug leads/drug targets, the problem
now has become one of specifi cally identifying such genes. Impeding this process is the fact that
the biological function of many sequenced gene products remains unknown. The focus of genome
research, therefore, is now shifting towards elucidating the biological function of these gene prod-
ucts, i.e. shifting towards 'functional genomics'.
Assessment of function is critical to understanding the relationship between genotype and phe-
notype and, of course, for the direct identifi cation of drug leads/targets. The term 'function' tra-
ditionally has been interpreted in the narrow sense of what isolated biological role/activity the
gene product displays (e.g. is it an enzyme and, if so, what specifi c reaction does it catalyse). In
the context of genomics, gene function is assigned a broader meaning, incorporating not only the
isolated biological function/activity of the gene product, but also relating to:
where in the cell that product acts and, in particular, what other cellular elements does it infl u-
ence/interact with;
how do such infl uences/interactions contribute to the overall physiology of the organism.
The assignment of function to the products of sequenced genes can be pursued via various ap-
proaches, including:
sequence homology studies;
phylogenetic profi ling;
Rosetta stone method;
gene neighbourhood method;
knockout animal studies;
DNA array technology (gene chips);
proteomics approach;
structural genomics approach.
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