A DNA repair gene may, ironically, be associated with the damage that occurs on Huntington’s disease.
Researchers at the National Institute of Neurological Disorders and Stroke (NINDS) of the National Institutes Health (NIH) came to that hypothesis after looking at their results of a unique study that examined genes, other than the Huntingin gene, in patients with the Huntington’s disease. Their study was published in the journal Cell1
and highlighted in a news release by the NIH.2
While it is well understood that Huntington’s disease is an inherited neurodegenerative disorder caused by mutations in the gene that encodes a protein called Huntingtin, the onset of the disease and the severity of the disease vary in this population. The new study at the NINDS may help explain some of the variance seen in this population.
In the NIH release, James Gusella, PhD, director of the Center for Human Genetic Research at Massachusetts General Hospital (MGH), Boston, and the corresponding author of the study said, “Our hope is to find ways that we can slow or delay the onset of Huntington’s devastating symptoms,” adding, “This could be possible because we now have a list of clinically proven genetic factors that influence the disease.”
The scientists employed a novel application of Genome Wide Association Study analysis, to not study the Huntington gene but other genes that seem to be associated with disease onset. The study used the patients’ DNA and clinical information to study the age when movement problems began. They found that 2 sites on chromosome 15 were strongly associated with disease onset. And 1 site was associated with accelerating the disease by an average of 6.1 years; while another site was associated with slowing the disease by about 1.4 years. A site on chromosome 8 was also associated with earlier disease onset (by approximately 1.6 years). Furthermore, some genetic changes were associated with DNA repair genes. While further studies are needed, the researchers noted in their abstract that the “results support a role for DNA handling and repair mechanisms in altering the course of Huntington’s disease.”1
A skyline view of Huntington’s disease obtained from the NIH and courtesy of Gusella lab, MGH, Boston.
Genetic Modifiers of Huntington’s Disease (GeM-HD) Consortium. Identification of Genetic Factors that Modify Clinical Onset of Huntington’s Disease. Cell. July 2015; Epub ahead of print. DOI: 10.1016/j.cell.2015.07.003
Scientists adopt new strategy to find Huntington’s disease therapies [news release]. Bethesda, MD: National Institute of Health; August 7, 2015. http://www.nih.gov/news/health/aug2015/ninds-07.htm