A six-team international research group that includes researchers from the Medical Center has identified the gene that causes Huntingtons disease, a progressive neurological disorder.
As reported in the March 26 issue of Cell, the Huntingtons Disease Collaborative Research Group isolated the new gene IT15 (IT stands for interesting transcript). The defective gene, carried by approximately one in 12,000 Americans, contains one segment of DNA that repeats too often.
Preliminary evidence indicates that there may be a rough correlation between the length of the repeated segment and the age of onset of Huntingtons disease in victims. The shorter the repeat, the older the victim will be when symptoms first appear. The longer the repeat, the younger the victim.
The search for the Huntingtons disease gene has been the most difficult gene hunt yet, says Francis S. Collins, leader of the U-M team. Its success now means that accurate diagnosis of Huntingtons disease will be almost immediately available, the basic biology of the disease can at last be understood, and the potential for new treatments can be vigorously pursued.
Furthermore, success in this endeavor bodes well for other gene discoveries in the future. With the advent of the Human Genome Project, such gene discoveries will occur at an ever-accelerating pace, adds Collins, who has been nominated to direct the National Center for Human Genome Research.
The Huntingtons gene discovery involved researchers in six groups drawn from Massachusetts General Hospital; Harvard Medical School; Boston University Medical School; Imperial Cancer Research Fund of London; Massachusetts Institute of Technology; California Institute of Technology; the University of California, Irvine; and the University of Wales College of Medicine.
The discovery of the Huntingtons gene is particularly gratifying because it was accomplished by a determined and talented group of collaborators spread across three continents who worked intensively and amicably for more than five years to achieve this goal, Collins says. The public sometimes gets the impression that science is a cutthroat business. The success of the Huntingtons collaboration provides a stunning counter-example, he adds.
The genetic defect causing Huntingtons disease was mapped to chromosome 4 in 1983 and since that time, researchers have been trying to isolate and characterize the Huntingtons gene.
Huntingtons disease is a progressive neurodegenerative disorder characterized by motor disturbance, cognitive decline leading to dementia, and psychiatric manifestations. Males and females are equally affected, and each offspring of an affected individual has a 50 percent chance of inheriting the disease.
The hallmark of Huntingtons disease is a distinctive jerky movement disorder that typically has a subtle, insidious onset between ages 25 and 60 and gradually worsens over the next 10 to 20 years until death. There currently is no treatment effective in delaying or preventing the onset and progression of the disease.
In addition to Collins, who also is a Howard Hughes Medical Institute investigator and professor of internal medicine and of human genetics, U-M team members are:
Danilo Tagle, John Valdes, Lawrence Elmer, Marc Allard, Lucio Castilla, Manju Swaroop, and Kris McQuate Blanchard, all of whom work in Collins laboratory.