Transposable elements, a common feature of the so-called “dark genome”, are associated with clinical differences in the progression of Parkinson’s disease in different people, according to a new study.
“Our main finding is that the presence or absence of [transposable elements] changes the progression trajectory of [Parkinson’s]and we have provided supporting clinical, imaging and biochemical evidence,” the researchers wrote.
“Non-reference genomic transposable elements (TEs) have a significant impact on the progression of Parkinson’s diseasewas published in Experimental biology and medicine.
It has long been known that the genetic code stored in DNA provides instructions for making proteins. But the parts of DNA that code for proteins make up less than 2% of the total human genome – the rest are non-coding elements whose function has only recently begun to be explored in detail.
Sulev Koks, MD, PhD, a professor at Murdoch University in Australia and first author of the study, calls these non-coding elements the “dark genome”.
“This fascinating study by Koks and colleagues demonstrates that the presence or absence of transposable elements controls the trajectory of progression of Parkinson’s disease. This further underscores the importance of rigorous analysis of these genomic elements is essential for considering therapeutic opportunities,” Steven Goodman, the journal’s editor, said in a press release.
One of the most abundant types of non-coding genetic sequences are transposable elements, or TEs. They are repetitive pieces of DNA that can “jump”, moving between different places in the overall genetic code.
“Transposable elements are part of the genome known as the ‘dark genome’. …Elements inside the dark genome could ameliorate or slow the progression of Parkinson’s disease and therefore open up new opportunities for precision medicine,” Koks said.
Koks and colleagues analyzed genetic data from 1,336 people with Parkinson’s disease, collected through the Parkinson’s Disease Progression Markers Initiative (PPMI) – a longitudinal observational study of people with and without Parkinson’s disease. Parkinson disease.
The researchers identified 16,438 ETs in this data. None showed a significant association with the risk of developing Parkinson’s disease in statistical models.
The team then looked for associations between ETs and changes in the severity of Parkinson’s disease over time in 423 patients followed for four years. This analysis included 3,374 SDs and more than 100 measures related to Parkinson’s disease.
The results showed many statistically significant associations. For example, more than 200 SDs showed significant associations with scores on the Unified Parkinson’s Disease Rating Scale (UPDRS), a common tool that measures the severity of Parkinson’s disease. There were about 150 TEs associated with degeneration of the putamen, a region of the brain heavily affected by the disease.
“We have identified many non-referral TEs to have an impact on the progression of [Parkinson’s]most remarkably on progression of UPDRS subscores and putamen degeneration,” the researchers wrote.
The team also identified many ETs associated with a primary diagnosis, the first condition patients were diagnosed with when they first started experiencing symptoms.
“Patients with certain ETs were more likely to receive an incorrect diagnosis at first visits that was corrected later. The change in diagnosis could indicate the difference in the [disease manifestations] subjects with different TE genotypes,” the researchers wrote, noting that this finding “may even suggest a distinct subtype of the disease.”
“Our study showed that the dark genome may have a much more significant impact on the pathophysiology of complex disease than previously estimated,” Koks said.
The study was designed only to detect associations, not cause-and-effect relationships. The researchers called for more research into how ETs affect Parkinson’s disease in laboratory models.
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