The investigation, spearheaded by Yuval Itan, a postdoctoral fellow in the St. Giles Laboratory of Human Genetics of Infectious Diseases, has led to the creation of what he calls the human gene connectome, the full set of distances, routes (the genes on the way), and degrees of separation, between any two human genes.
Itan, a computational biologist, says the computer program he developed to generate the connectome uses the same principles that GPS navigation devices use to plan a trip between two locations. The research is reported in the online early edition of the journal Proceedings of the National Academy of Sciences.
"High throughput genome sequencing technologies generate a plethora of data, which can take months to search through," says Itan. "We believe the human gene connectome will provide a shortcut in the search for disease-causing mutations in monogenic diseases."
Itan and his colleagues, including researchers from the Necker Hospital for Sick Children, the Pasteur Institute in Paris, and Ben-Gurion University in Israel, designed applications for the use of the human gene connectome. They began with a gene called TLR3, which is important for resistance to herpes simplex encephalitis, a life-threatening infection from the herpes virus that can cause significant brain damage in genetically susceptible children. Researchers in the St. Giles lab, headed by Jean-Laurent Casanova, previously showed that children with HSE have mutations in TLR3 or in genes that are closely functionally related to TLR3. In other words, these genes 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 genetic mechanisms."
Joseph Bonner | EurekAlert!
Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery
20.01.2017 | GSI Helmholtzzentrum für Schwerionenforschung GmbH
Seeking structure with metagenome sequences
20.01.2017 | DOE/Joint Genome Institute
An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...
Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
19.01.2017 | Event News
10.01.2017 | Event News
09.01.2017 | Event News
20.01.2017 | Awards Funding
20.01.2017 | Materials Sciences
20.01.2017 | Life Sciences