Gene discovery >> Gene Diversity >> Gene products to dissect the relationship between gene sequence, expression
and function and disease predisposition, progression and therapy. The trend is moving toward personalization of medicine at the genetic level.
In the discovery genetics, the biochemistry of human disease populations permits to identify disease-related susceptibility genes. This represents the basis
for pharmacogenetics: Biochemistry  Pharmacogenetics Genomics is the activity that identifies the relationships between genes, health and disease. Discovery genomics
uses the DNA sequence information to identify genes for tractable or screenable targets that are not known to be genetically related to disease. The translation of functional genomics into rational therapy corresponds to
pharmacogenomics. The end-point of pharmacogenomics is then the ability to target a drug specifically to those genotypically defined patients who will repond well to the drug with no adverse side effects. Pharmacogenomics
may also enable the rescue and retargeting of drugs that failed in clinical trials due to toxicity or low efficacy [W. E. Evans and M. V. Relling - Science 286 (1999), 487 - 491; Allen D. Roses - Nature
405 (2000), 857-865 ]. Genomics Pharmacogenomics
A clinical alternative to the premise of pharmacogenomics and a less costly method (compared to genetics-based pharmacogenomic approach) is that represented by "metaprobes
", chemicals with the function of measuring specific enzyme activity relevant to a disease process or biochemical patway . Proteomics
identifies and relates the expression and location of proteins to disease predisposition, progression and drug toxicology and pharmacology. Expanding the 1950s Biology Dogma
Today: 
One gene  More proteins
as a consequence of (i) post-translational processes, (ii) alternative splicing, (iii) rearrangement of the number and the order of proteins domains encoded within genes, (iv) regulation of gene expression (role of the
transcription factors), (v) the Wright & Dyson's "intrinsic disorder" under physiological / pathological conditions.
"Like the Greek sea god Proteus, who could change form at will (Homer, in: "The Odyssey", book IV, 349 - 570), proteins can assume myriad shapes and structures, and even shift from begnin to cancer-causing
molecules and then back again, so studying them is not so easy task." [in "Protein Shaker" by Stephan Herrera, in: Red Herring 79, 359 - 366 (2000)]
Unlike genomics (which involves the analysis of simple repeating polymers), proteomics involves the study of very complex heteropolymers having a wide range of sizes, physical properties, secondary and tertiary
structures, solubilities, and functions (the Karush's configurational adaptability)c. Eritable changes in gene expression ,that occur without a change in DNA sequence, can complicate the genetic
manipulation of living organisms. Epigenetics
is the study of these phenomena. "essential for normal
development, epigenetic controls become misdirected in cancer cells and other human disease syndromes" ["The organizing principle: microenvironmental influences in the normal and malignant breast" by Mina J. Bissell et al. on:
Differentiation 70 , 537 - 546 (2002); "Epigenetics: Genome, Meet Your Environment" by Leslie A. Pray on: The Scientist 18
(13), 14 - 20 (2004); "Cancer epigenetics enters the mainstream" by Mark Greener on: The Scientist 19 (12), 18 - 19 (2005); " Epigenetics provides a new generation of oncogenes and tumour-suppressor genes" by Esteller M on: Br J Cancer.96
Suppl:R26-30 (2007)]
Different aspects of epigenetic inheritance
Lamarckism Revisited |
RNA interference |
Transcriptional silencing |
Chromatin-based events |
X inactivation |
DNA methylation and transposon activity |
Cloning of mammals by nuclear transfer (NT) |
The centromere |
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