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New DNA clues to Parkinson’s disease risk

Overview: Alterations in nascent transcription of introns may indicate risk factors for and progression of Parkinson’s disease.

Source: Murdoch University

The findings of a new Parkinson’s disease study have opened an exciting avenue for developing therapies to intervene in the progression of this common movement disorder.

The main article in Experimental biology and medicine contributes to the understanding of genetic processes underlying nerve cell degeneration in people with Parkinson’s.

The study, led by Professor Sulev Koks of the Perron Institute for Neurological and Translational Science in Western Australia and Murdoch University, reports that changes in nascent transcription of introns (related to DNA sequencing) may be indicators of risk and the progression of Parkinson’s.

“A better understanding of the mechanisms underlying nerve cell degeneration could help develop targeted therapies for people with Parkinson’s,” said Professor Koks.

“For years, the search for DNA risk factors for specific diseases like Parkinson’s has focused on exons, the two percent of our genome that encode the information for proteins.

“Most of the DNA risk is in the other 98 percent of the genome that determines where, when and how long exons are produced to generate these proteins.

“Likewise, previous research has focused on measuring exons in specific cells, ignoring the bulk of non-exon material that can affect their function.”

This shows a person holding a DNA strand
The study showed the importance of introns in regulating cell function and causing changes. Image is in the public domain

In this study, Professor Koks, Dr. Abigail Pfaff (Perron Institute and Murdoch University) and Dr. Vivien Bubb and John Quinn of the University of Liverpool introns and examined changes linked to the progression of Parkinson’s disease.

The study showed the importance of introns in regulating cell function and causing changes.

“Our study highlights the importance of introns as potential modulators that regulate cell function by manipulating how exons are used in the cell,” said Professor Koks.

“This work opens a new avenue of genomic research to develop novel approaches for better diagnosis and more targeted therapeutic intervention in the progression of Parkinson’s disease.”

The article is titled “Longitudinal Intronic RNA-Seq Analysis of Patients with Parkinson’s Disease Reveals Disease-Specific Nascent Transcription.”

dr. Steven Goodman, editor-in-chief of Experimental biology and medicinesaid the study illustrates additional blood-based biomarkers that are potentially predictive of risk and diagnostic of the progression of Parkinson’s disease.

About this news about genetics and Parkinson’s disease

Author: press office
Source: Murdoch University
Contact: Press Office – Murdoch University
Image: The image is in the public domain

Original research: Open access.
Longitudinal intronic RNA-Seq analysis of patients with Parkinson’s disease reveals disease-specific nascent transcriptionby Sulev Koks et al. Experimental biology and medicine

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Longitudinal intronic RNA-Seq analysis of patients with Parkinson’s disease reveals disease-specific nascent transcription

Transcriptomic studies mostly focus on gene or exon-based annotations, and only limited experiments have reported changes in the mapping of reads to introns. The analysis of intronic reads allows for the detection of nascent transcription unaffected by steady-state RNA levels and provides information on actively transcribed genes.

Here we describe substantial intron transcriptional changes in patients with Parkinson’s disease (PD) compared to healthy controls (CO) at two different time points; at the time of diagnosis (BL) and three years later (V08).

We used blood RNA-Seq data from the Parkinson’s Progression Markers Initiative (PPMI) cohort and identified significantly altered transcription of intronic reads only in PD patients during this follow-up period.

In CO patients, only nine transcripts showed differentially expressed introns between visits. However, in PD patients, 4873 transcripts had differentially expressed introns at visit V08 compared to BL, many of them in genes previously associated with neurodegenerative diseases, such as LRRK2C9orf72LGALS3CHANCEL1AS1and IF2

In addition, at the time of diagnosis (BL visit), we identified 836 transcripts (e.g., SNCADNAJC19PRRG4) and at visit V08, 2184 transcripts (eg PINK1GBAIF2PLEKHM1) with differential intronic expression specific to PD patients. In contrast, read-mapping to exonic regions showed little variation, indicating very specific changes only in intronic transcription.

Our study showed that PD is characterized by substantial changes in nascent transcription, and a description of these changes could help to understand the molecular pathology underlying this disease.

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