Update 2009 Genomics Is Medicine ready for Genome Sequencing?

Genetics news has been commonplace for many years, complete with premature promises of revolutionary new medical treatments. These inflated expectations are certain to disappoint the uninitiated. The unfolding science reveals more complexity and uncertainty with each discovery. New methods emerge quickly that empower scientists to discover more, faster and at lower cost, but there is no assurance that new discoveries will take us closer to practical applications, rather than farther away from affordable medical miracles.

In their description of the National Human Genome Research Institute’s Encyclopedia of DNA Elements (ENCODE) project, Guigó and Reese stated:  “Finding human genes is a complex task because of the peculiar anatomy of the eukaryotic genome. Eukaryotic genes lie within long stretches of intergenic DNA, and within the genes only a few short fragments—the exons—are spliced together, often in alternative configurations, to form the mRNAs. Sequence signals in the genome are degenerate, and computational programs using them are able to identify the exons and link them into genes with relative success. But only through the sequencing of the corresponding mRNA molecule can a gene be unequivocally identified. It is unclear, however, what fraction of genes can be ascertained through mRNA sequencing. In addition, genes are only one type of functional elements. It is likely that most of the functionality of the human genome sequence remains largely unexplored.”    

The modest aim of the first phase of ENCODE was to identify all functional elements in about 1% of the genome sequence through the collaborative effort of computational and laboratory-based scientists.   In time, the genomes of many species and many individuals within a species will be determined. Sophisticated comparative analyses of genomes will reveal more about the evolution of species. Computers with increasingly sophisticated software are essential to using genomic information in meaningful ways.  DNA sequencing, brilliant programming and digital computing are perfect matches.

In medical papers, old ideas of genes often prevail. Phrases such as genetic tendency, genetic component, and genes play a role in are typical of obsolete generalities that confuse rather than inform. The new appreciation that genes are not solid, real entities is difficult for physicians to understand. Part of the problem is that medical education pretends that humans are static entities and that diseases are discrete phenomena. A dynamic, interactive systems model better accounts for what actually happens. Rather than genes, you could imagine segments of DNA as code that is read differently depending on circumstances. Much of the code with deals with getting food, digesting it, distributing nutrients, and excreting waste products. Food intake to the body is a major player in determining gene expression.

While there is great interest in developing rapid, inexpensive genome sequencing, we lack even the most basic understanding of how to read the genomic data. The predication of disease risk is the least likely result of genomic data. Since the code is interactive, the expression of any sequence associated with a disease may altered by changing food intake or other variables in the environment.