A team of researchers have shown how transposable elements are associated with Parkinson’s subtypes and impact disease trajectory.
A study, which involved University of Liverpool researchers, analysed the variation of transposable elements which are DNA sequences that have the ability to change their position within a genome and their impact on different trajectories of Parkinson’s disease.
Parkinson’s disease is a condition that affects parts of the brain, subsequently, they come become progressively damaged over many years. Parkinson’s causes three main symptoms which are involuntary shaking, slow movement and stiff, inflexible muscles.
The study is published in Experimental Biology and Medicine.
What are transposable elements?
Transposable elements make up over 70% of the human genome. However, they have always been considered as ‘junk’ DNA without any meaningful function. These elements have been ignored in most genetic studies; there is a possibility they could contribute to unknown genetic factors that influence disease development.
Previous studies have shown the elements have a significant role in the genome, acting as a regulatory elements. They regulate the expression of many genes, orchestrate complex genetic activation where multiple genes are needed for a complex response, and the growing body of evidence suggests that the transposable elements have a major pathogenic effect, with several elements shown to cause disease.
Studying how DNA sequences affect Parkinson’s
The researchers used patient data from the Parkinson’s Progression Markers initiative, one of the largest international longitudinal cohorts of Parkinson’s patients, funded by the Michael J. Fox Foundation, from patients who also had whole genome sequencing data available. This allowed researchers to develop a comprehensive genomic screen for the transposable elements in these patients and to detect their impact on disease progression.
The researchers discovered that transposable elements were associated with Parkinson’s subtypes and disease trajectory. Some transposable elements in a patient’s genome predicted faster progression of the disease, with quick deterioration of motor or cognitive functions.
Furthermore, some elements were associated with a strong and clinically meaningful change in functional Parkinson’s scores, including a 40-point change in the Unified Parkinson’s Disease Rating Scale. Simultaneously, some transposable elements were protective and associated with a slower disease progression suggesting a slowing of neuronal loss and neurodegeneration.
“Transposable elements are part of the genome which is known as the ‘dark genome’”, senior author Professor Sulev Koks said. “Our study showed that the dark genome may have a much more significant impact on the pathophysiology of complex disease than previously estimated.”
“The elements inside the dark genome could enhance or slow the progression of Parkinson’s disease and therefore open up new opportunities for precision medicine.”