Now two major revolutions, one genomic and one in informatics, are completely changing the face of preventive medicine. Every day all over the world, millions of genetic sequences — from disease-related genes to complete genomes of plants, animals, bacteria and viruses — are resolved, identified and dissected.
One Israeli researcher is using this information to tell patients which diseases they are at risk of contracting and to construct genetic sequences that could protect people from such diseases in the future. Dr. Yuval Tabach, a researcher from IMRIC -- the Institute for Medical Research Israel‑Canada at the Hebrew University – has developed a new Internet tool that will allow any investigator, physician or patient to analyze a gene according to its evolutionary profile, in order to alert patients of imminent genetic diseases and cancer.
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Genes are our biological fortune-tellers
One example of a known mutation which increases the likelihood of developing breast and ovarian cancers is in the BRCA1 gene. Interest in this gene was highlighted when Angelina Jolie discovered that she had inherited the dangerous mutation from her mother, who died of cancer aged 56. However in the majority of cases, both for breast cancer and other genetically transmitted diseases, the identity of the gene responsible for the disease is unknown.
By using the methods of genetic analysis developed by Dr. Tabach, researchers can now identify genes within the same network as the BRCA1 gene, or other associations of genes, simply by scanning the evolutionary profiles of tens of organisms with a single click. The number of organisms that can be scanned in this way is anticipated to increase to hundreds in the near future.
The technique is simple and based on the fact that genes that work together or those that play an important role in biology will be present together in organisms that need them. Conversely, genes connected to a particular function like vision will disappear from species that have lost the power of sight, and may therefore be identified by a comparison to the genes in normal animals.
Dr. Tabach’s application is a product of his continued research, which he began as a Fellow at Harvard University in collaboration with researchers and physicians from all over the world. This research revealed the possibility of comparing the evolutionary profiles derived from multiple organisms to predict the biological functions and clinical relevance of given genes. One of the most important applications of this approach is the possibility to identify genes associated with genetic diseases and cancer.
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“The significance of this tool is that anyone, physician or researcher, can input results from genetic mapping studies concerning suspected genes, and the tool will identify evolutionary, and probably functional, connections to known genes with association to diseases” explains Dr. Tabach. “The process is rapid, without cost or time wasted, and enables the identification of genes responsible for diseases.”
Identifying the vampires among us?
An interesting example of a gene that could be identified using this phylogenetic profiling approach is the so-called “Vampire’s Disease,” more professionally termed porphyria. Representing a family of genetic diseases characterized by abdominal pain, sensitivity to sunlight, purple urine, and psychotic episodes, porphyria probably forms the basis for the prevalent myths of vampires. These diseases are rare, but there is evidence for hereditary porphyria in European royal families, and it may have been responsible for the madness of King George III, as well as for the psychotic behavior of the painter Vincent Van Gogh, misdiagnosed as a depressive schizophrenic. Dr. Tabach demonstrated how, with one click, it is possible to identify essentially all the genes known to be associated with porphyria as well as other genes that, based on their phylogenetic profile, are very likely to be involved.
Vincent Van Gogh
The bioinformatics methods developed by Dr. Tabach have formed the basis for the establishment of a company dealing with computational pharmaceutics which will identify new indications for existing therapeutic agents. This could dramatically decrease the time and expense required to bring a new drug to market, and facilitate the development of treatments for rare orphan diseases.
In the coming years, Dr. Tabach’s laboratory intends to focus on the identification of genes that prevent aging and protect against cancer, by consideration of the genes of some fascinating species of organisms with increased longevity and an almost complete resistance to cancer. In addition the laboratory is working with a model which describes almost 40 neurological diseases with a related etiology including Huntington’s disease, ataxia, and fragile X‑syndrome.
The research paper, co-authored with collaborators from Massachusetts General Hospital and Harvard Medical School in Boston, appears in the journal Nucleic Acids Research as “PhyloGene server for identification and visualization of coevolving proteins using normalized phylogenetic profiles”. Support for the research came from Hebrew University of Jerusalem start-up funds.
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