Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK.
Perron Institute for Neurological and Translational Science, Perth, WA, Australia.
Sci Rep. 2024 May 13;14(1):10932. doi: 10.1038/s41598-024-61753-5.
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.
SINE-VNTR-Alu（SVA）反转录转座子是遗传变异的来源之一。我们之前的研究表明，一种名为 SVA_67 的人类特异性 SVA 的存在/缺失与帕金森病（PD）的进展相关。在本研究中，我们利用帕金森病进展标志物倡议队列的全基因组和转录组数据，证明 SVA_67 作为表达数量性状基因座，在整个基因组中表现出强烈的调控作用。我们进一步表明，SVA_67 的可变数串联重复结构域具有多态性，这与其在体外荧光素酶报告基因检测中的调控特性以及体内多个基因的差异表达相关。此外，这种变异作为生物标志物的效用体现在与许多 PD 进展标志物的相关性上。这些实验突出了与 SVA_67 多态性相关的大量转录组和表型变化，在研究神经退行性疾病的遗传缺失时应考虑这些变化。
