Deciphering the role of a SINE-VNTR-Alu retrotransposon polymorphism as a biomarker of Parkinson’s disease progression

Alexander Fröhlich; Abigail L Pfaff; Ben Middlehurst; Lauren S Hughes; Vivien J Bubb; John P Quinn; Sulev Koks

doi:10.1038/s41598-024-61753-5

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Deciphering the role of a SINE-VNTR-Alu retrotransposon polymorphism as a biomarker of Parkinson’s disease progression

Journal article

Open access

Peer reviewed

Deciphering the role of a SINE-VNTR-Alu retrotransposon polymorphism as a biomarker of Parkinson’s disease progression

Alexander Fröhlich, Abigail L Pfaff, Ben Middlehurst, Lauren S Hughes, Vivien J Bubb, John P Quinn and Sulev Koks

Scientific reports, Vol.14(1), 10932

2024

DOI: https://doi.org/10.1038/s41598-024-61753-5

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Abstract

Biomarkers

DNA sequences

Gene mapping

Gene polymorphism

Genetic diversity

Genetic variation

Genomes

Heritability

Movement disorders

Neurodegenerative diseases

Parkinson's disease

Polymorphism

Quantitative trait loci

Reporter gene

Short interspersed nucleotide elements

Transcriptomics

SINE-VNTR-Alu (SVA) retrotransposons are transposable elements which represent a source of genetic variation. We previously demonstrated that the presence/absence of a human-specific SVA, termed SVA_67, correlated with the progression of Parkinson’s disease (PD). In the present study, we demonstrate that SVA_67 acts as expression quantitative trait loci, thereby exhibiting a strong regulatory effect across the genome using whole genome and transcriptomic data from the Parkinson’s progression markers initiative cohort. We further show that SVA_67 is polymorphic for its variable number tandem repeat domain which correlates with both regulatory properties in a luciferase reporter gene assay in vitro and differential expression of multiple genes in vivo. Additionally, this variation’s utility as a biomarker is reflected in a correlation with a number of PD progression markers. These experiments highlight the plethora of transcriptomic and phenotypic changes associated with SVA_67 polymorphism which should be considered when investigating the missing heritability of neurodegenerative diseases.

Details

Title: Deciphering the role of a SINE-VNTR-Alu retrotransposon polymorphism as a biomarker of Parkinson’s disease progression
Authors/Creators: Alexander Fröhlich - University of Liverpool
Abigail L Pfaff - Perron Institute for Neurological and Translational Science
Ben Middlehurst - University of Liverpool
Lauren S Hughes - University of Liverpool
Vivien J Bubb - University of Liverpool
John P Quinn - University of Liverpool
Sulev Koks - Perron Institute for Neurological and Translational Science
Publication Details: Scientific reports, Vol.14(1), 10932
Publisher: Nature Publishing Group
Identifiers: 991005664670007891
Murdoch Affiliation: Centre for Molecular Medicine and Innovative Therapeutics
Language: English
Resource Type: Journal article

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