Autism is also puzzling to scientists because it is heartbreaking for parents. Some patients function well despite some behavioral quirks, while others are profoundly disabled. The dozens of "suspicious genes" are scattered among different types of the disease and appear in only a handful of patients. Now, shifting the focus from genes to proteins they produce, the researchers identified a denser network that can help reveal how autism develops. The finding may also lay the framework for the development of new treatments, even for very different types of the disease.
The inspiration for a network of protein came from research geneticist Marc Vidal of the Dana-Farber Cancer Institute in Brookline, Massachusetts. Vidal had mapped the first of these networks-later known as interactomes in the wake of the Human Genome Project. "The Human Genome Project gave us a parts list," says Vidal. "By studying how proteins interact, we could see how the parts are assembled."
The proteins that work together inside cells sometimes physically touch each other;. often, many of them also link to some core proteins that play a key role in a particular biological process a resulting relationship diagram may look like a ball Koosh interconnection lines radiating from one or more platforms (see photo).
in a study published in 06 cell , and Huda Zoghbi Vidal, a neurobiologist at Baylor College of Medicine in Houston, Texas, teamed to show unsuspected interactions between proteins produced by the mutated genes in a number of movement disorders known as ataxias name. the fact that the "protein products" genes seemingly unrelated work actually all referred to a common process through which the different types of ataxias occur.
In the new study, Zoghbi and her colleagues studied the interaction of proteins in the complex disorder of autism. The researchers used protein "bait" of more than two dozen known autism genes, fishing in a pool of human DNA to other proteins that interact with bait. If the proteins bind to each other through repeated testing, it is a sign that they cooperate in a biological process, and not just to jam together.
Using more sensitive screening methods, researchers eventually have "taken" over 500 proteins that form connections with 26 bait protein and interacted with each other.
The fact that so many proteins interact with protein bait 26 indicates that these original proteins play a key role in a complex process that has not been apparent in the genes "suspects". Since these genes are from different types of autism, the process alluded to what may be a common feature.
The emerging pathway is probably a problem that occurs at the synapse, the contact point between neurons, Zoghbi said. It has long argued that autism and other neurodevelopmental disorders can result from poor connections at these junctions, but the possibility of a yarn highlighted by the complex interactions related to protein-common autism is encouraging said Zoghbi. His team presents its findings online today in Science Translational Medicine.
Two proteins called TAIL and TSC1, which are involved in very different syndromes related to autism who are not thought to be related, proved 21 to be connected by other proteins. In addition, when the researchers checked their network against the DNA of patients with non-syndromic, or "stand-alone" autism, they found abnormalities involving three network genes. Both findings suggest that different types of autism may share a common pathway, even when they occur in single or separate syndromes, something that was not clear while watching the genes.
These common pathways are promising targets for drug development, said Zoghbi. "Our interactome is only a first step, but it could lead to a framework to study new genes and to test new drugs."
"interactomes like this one do all the genes of debate over the much more sophisticated environment, "adds Vidal, who was not involved in the current study and mapped a network involved in the predisposition to breast cancer in 07." to understand how genes lead to disease, interactomes give us the best of both worlds. "
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