09:57am Wednesday 13 November 2019

UM Researchers Sequence Rare Variants Associated With Parkinson Disease

he findings of their study, “Whole exome sequencing of rare variants in EIF4G1 and VPS35 in Parkinson disease,” were published online this month in the journal Neurology.

Led by senior author Jeffery M. Vance, M.D., Ph.D., professor of human genetics and neurology, the investigators are among the first to use whole exome sequencing to evaluate rare variants in Parkinson disease. The journal recognized the accomplishment with an accompanying editorial, “The importance of rare DNA variation in neurologic disease.”

Parkinson disease is the second most common neurodegenerative brain disorder, affecting about 2 percent of the population over age 65.

In addition to Vance, other UM coauthors on the study included first author Karen Nuytemans, Ph.D., Vance’s post-doctoral fellow, Liyong Wang, Ph.D., research assistant professor, Stephan Züchner, M.D., Ph.D., associate professor of human genetics and neurology and Interim Chair of the Dr. John T. Macdonald Foundation Department of Human Genetics, Gary W. Beecham, Ph.D., assistant professor of human genetics, Eden R. Martin, Ph.D., professor of human genetics, William K. Scott, Ph.D., professor of human genetics, Guney Bademci, M.D., former assistant scientist, Vanessa Inchausti, research associate, Amy Dressen, former senior research analyst, Daniel D. Kinnamon, M.S., student research assistant, and Arpit Mehta, M.S., senior systems analyst.

“We hope that identification of these rare variants through whole exome sequencing will help the field determine which genes, and more specifically which variants with low frequency but higher chance of causing disease, are involved in Parkinson disease,” said Vance, who serves as Director and primary principal investigator of the NIH Morris K. Udall Parkinson Disease Research Center of Excellence, now in its 13th year of funding. He is an internationally recognized leader in identifying genes associated with neurodegenerative diseases, such as Parkinson and Charcot-Marie-Tooth disease.

Vance and his team performed whole exome sequencing on 213 Parkinson patients and 272 control individuals. They set out to use the advantages of whole exome sequencing to investigate the genetic involvement of the recently identified genes EIF4G1 and VPS35 in the development of Parkinson disease, both on a single variant and gene level.

The results confirmed a variation in the gene EIF4G1 appeared to be a strong risk factor for developing Parkinson disease. Other rare variants could not be ruled out as being causal. But there was no evidence for overall contribution in either VPS35 or EIF4G1 in the researchers’ dataset.

The researchers of the Miami Udall Center have expanded the group of patients and control individuals in their study to a total of 850 and will continue to analyze the vast amount of rare variants they identified in known Parkinson disease genes, as well as compare the data in both groups to identify new candidate genes for Parkinson disease.

University of Miami

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