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Researchers create map of 'shortcuts' between all human genes
Date:3/18/2013

es are located at a short biological distance from TLR3. As a result, novel herpes simplex encephalitis-causing genes are also expected to have a short biological distance from TLR3.

To test how well the human gene connectome could predict a disease-causing gene, the researchers sequenced exomes all DNA of the genome that is coding for proteins of two patients recently shown to carry mutations of a separate gene, TBK1.

"Each patient's exome contained hundreds of genes with potentially morbid mutations," says Itan. "The challenge was to detect the single disease-causing gene." After sorting the genes by their predicted biological proximity to TLR3, Itan and his colleagues found TBK1 at the top of the list of genes in both patients. The researchers also used the TLR3 connectome the set of all human genes sorted by their predicted distance from TLR3 to successfully predict two other genes, EFGR and SRC, as part of the TLR3 pathway before they were experimentally validated, and applied other gene connectomes to detect Ehlers-Danlos syndrome and sensorineural hearing loss disease causing genes.

"The human gene connectome is, to the best of our knowledge, the only currently available prediction of the specific route and distance between any two human genes of interest, making it ideal to solve the needle in the haystack problem of detecting the single disease causing gene in a large set of potentially fatal genes," says Itan. "This can now be performed by prioritizing any number of genes by their biological distance from genes that are already known to cause the disease.

"Approaches based on the human gene connectome have the potential to significantly increase the discovery of disease-causing genes for diseases that are genetically understood in some patients as well as for those that are not well studied. The human gene connectome should also progress the general field of human genetics by predicting the nature of unknown gene
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Contact: Joseph Bonner
joseph.bonner@rockefeller.edu
212-327-8998
Rockefeller University
Source:Eurekalert

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