For the study, researchers analyzed the genes of 278 people with Parkinson's disease and 179 people without the disease.

The study found 14 percent of the people with Parkinson's disease carried mutations in the glucocerebrosidase (GBA) gene compared to only five percent of people without the disease. The gene abnormality was found in 22 percent of people who were diagnosed with Parkinson's disease before age 50 compared to 10 percent of the people with disease onset after age 50. Mutations in the GBA gene cause Gaucher's disease, which is a rare disorder that prevents organs, such as the spleen and brain, from working properly due to the build-up of a fatty substance called glucocerebroside.

Our results confirm that GBA mutations are risk factors for Parkinson's disease and may lead to getting the disease at a younger age, said study author Lorraine N. Clark, PhD, and coauthor Karen Marder, MD, MPH, with Columbia University's Taub Institute for Research on Alzheimer's Disease and the Aging Brain, and Departments of Pathology and Neurology, in New York. We found those people with GBA mutations developed Parkinson's disease nearly two years earlier than people without the gene abnormality.

The study also looked at how Jewish ancestry affected the likelihood of getting Parkinson's disease at an earlier age since some studies have found people with Jewish ancestry are more likely to have GBA mutations.

Of those with Parkinson's disease, researchers found the gene abnormality in 17 percent of the participants with Jewish ancestry compared to only eight percent of those without Jewish ancestry, suggesting that it may be an important risk factor in people with Jewish ancestry.

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The instructions frequently come through a mechanism known as DNA methylation, which the body uses often to turn genes off. Normally, such chemical markings are wiped clean and reset very early in an organism's life through a process known as epigenetic reprogramming. But Li's team showed that JAK “ specifically an activated JAK kinase known as HOP-Tum-l “ can disrupt that reprogramming, so that the offspring inherit the methylation pattern of a parent. In other words, the specific pattern of genes that are destined to be turned on or off “ the instructions for what to do with the DNA “ is mistakenly passed on from parent to offspring.

While scientists have known that epigenetic information can be passed from generation to generation, Li says this is the first time the phenomenon has been linked to a cancer-causing gene.

To do the study, Li's team focused on the interaction between JAK and a gene known as Kr ppel, best known for playing a major role in the development of a fruit fly's body. It turns out that Kr ppel also enhances an organism's ability to suppress tumors, and if the normal gene is knocked out or replaced by a faulty version, an organism is more likely to develop cancer when another cancer-causing gene like JAK is present.

His team found that some flies with a normal version of Kr ppel got just as many tumors as their brethren with the bad copy “ about three times as many tumors as most fruit flies with the normal version “ simply because one of their parents harbored the JAK oncogene. Scientists believe the JAK mutation somehow messed up the package that contained Kr ppel, and this damage causes problems a generation later, even when the faulty Kr ppel gene is no longer around.

In Jurassic Park, all the knowledge that was needed to re-create dinosaurs was gotten out of ancient DNA embedded in amber, said Dirk Bohmann, Ph.D., a colleague and fellow fruit-fly researcher who was not directly involved in the study. Willis and other scientists are showing that there is so much more that goes into controlling and regulating genetic information than just knowledge of the DNA code. Michael Crichton would have a harder time making that film today, given what has been discovered in recent years.

This work tells us that we have to pay more attention to the ways in which DNA is packaged. It's not just about the DNA sequence, Bohmann added.

Last year in a paper in Nature Genetics, Li first showed that JAK is a more powerful oncogene than previously thought, with the ability to turn on cancer-causing genes that are normally silent, through another epigenetic mechanism involving gene packaging. The new work shows that the gene is also able to suppress cancer-suppressing genes that are normally turned on, making JAK even more of a threat than had been known.

Work like Li's is getting the attention of pharmaceutical companies, which are developing drugs that target an organism's DNA governance at the epigenetic or packaging level. Such work provides a new target for developing drugs to stop cancer, and it reminds scientists just how much more research is necessary before we fully understand the workings of ACTGGGCTAGTTGGCAGT and the countless other DNA sequences in our body.

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