A new study is helping scientists zero in on the genes that may confer susceptibility to Parkinson's disease. In what is called a whole-genome association study, Demetrius Maraganore and colleagues at the Mayo Clinic and Perlegen Sciences Inc. took blood samples from more than 1,500 individuals, including patients with the disease, siblings who did not have the disease, and unrelated, healthy control subjects.
The DNA of each individual was compared against a "library" of genetic variations called single nucleotide polymorphisms (SNPs) in the hope of finding a unique signature for Parkinson's disease.
SNPs (pronounced "snips") broke onto the research scene in the late 1990s and have become increasingly valuable research tools. A SNP occurs when a single nucleotide (the building blocks paired together to make the double helix of DNA) is substituted for another. When multiple SNPs are found near each other in similar patterns in the DNA of siblings or people with inherited diseases, these SNPs are thought to underlie an inherited trait or disease. Hundreds of thousands of SNPs have been identified and are available for comparison.
In a study published in the November issue of the American Journal of Human Genetics, Maraganore and colleagues sifted through about 200,000 SNPs. The researchers identified a number of SNPs occurring in two genes, called PARK10 and PARK11, that previous studies had found to be abnormal in people with Parkinson's disease. By comparing the DNA of patients who had the disease to family members who did not, as well as to unrelated controls, the investigators provided convincing evidence that the SNPs are involved with Parkinson's disease and not with some other family trait.
The team also identified about 10 additional SNPs that may confer disease vulnerability, many of them in intriguing locations. One such SNP, in a gene called SEMA5a, is thought to be involved in the development and programmed death of dopamine-producing cells-the population of neurons that dies off in the disease.
"Our findings may identify markers of the disease that can help with early detection and prevention. They may also point to new targets for therapy," Maraganore concludes.