Author:
Fröhlich Alexander,Pfaff Abigail L.,Middlehurst Ben,Hughes Lauren S.,Bubb Vivien J.,Quinn John P.,Koks Sulev
Abstract
AbstractSINE-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.
Funder
MSWA and Perron Institute for Neurological and Translational Science
Motor Neurone Disease Association
Andrzej Wlodarski Memorial Research Fund
Andrzej Wlodarski Memorial Research PhD scholarship
Darby Rimmer Foundation
Publisher
Springer Science and Business Media LLC
Cited by
1 articles.
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