Characterisation of the Function of a SINE-VNTR-<i>Alu</i> Retrotransposon to Modulate Isoform Expression at the <i>MAPT</i> Locus

Frohlich, Alexander, Pfaff, Abigail L, Bubb, Vivien J ORCID: 0000-0003-2763-7004, Koks, Sulev ORCID: 0000-0001-6087-6643 and Quinn, John P ORCID: 0000-0003-3551-7803
(2022) Characterisation of the Function of a SINE-VNTR-<i>Alu</i> Retrotransposon to Modulate Isoform Expression at the <i>MAPT</i> Locus. FRONTIERS IN MOLECULAR NEUROSCIENCE, 15. 815695-.

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SINE-VNTR-<i>Alu</i> retrotransposons represent one class of transposable elements which contribute to the regulation and evolution of the primate genome and have the potential to be involved in genetic instability and disease progression. However, these polymorphic elements have not been extensively analysed when addressing the missing heritability of neurodegenerative diseases, including Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS). SVA_67, a retrotransposon insertion polymorphism, is located in a 1.8 Mb region of high linkage disequilibrium, called the <i>MAPT</i> locus, which is known to contribute to increased risk of developing PD, frontotemporal dementia and other tauopathies. To investigate the role of SVA_67 in directing differential gene expression at this locus, we characterised the impact of SVA_67 allele dosage on isoform expression of several genes in the <i>MAPT</i> locus using the datasets from both the Parkinson's Progression Markers Initiative and New York Genome Center Consortium Target ALS cohort. The Parkinson's data was from gene expression in the blood and the ALS data from a variety of CNS regions and allowed us to demonstrate that SVA_67 presence or absence correlated with both isoform- and tissue-specific expression of multiple genes at this locus. This study highlights the importance of addressing SVA polymorphism in disease genetics to gain insight into a better understanding of the role of these regulatory domains to a variety of neurodegenerative diseases.

Item Type: Article
Uncontrolled Keywords: transposable elements, MAPT, tau, Parkinson's disease, ALS, FTD, motor neuron disease, SVA
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User: Symplectic Admin
Date Deposited: 05 Apr 2022 15:25
Last Modified: 14 Oct 2023 18:55
DOI: 10.3389/fnmol.2022.815695
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