Exploring SVA Insertion Polymorphisms in Shaping Differential Gene Expressions in the Central Nervous System.

Hughes, Lauren S, Fröhlich, Alexander, Pfaff, Abigail L, Bubb, Vivien J ORCID: 0000-0003-2763-7004, Quinn, John P ORCID: 0000-0003-3551-7803 and Kõks, Sulev (2024) Exploring SVA Insertion Polymorphisms in Shaping Differential Gene Expressions in the Central Nervous System. Biomolecules, 14 (3). p. 358.

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Official URL: http://dx.doi.org/10.3390/biom14030358

Abstract

Transposable elements (TEs) are repetitive elements which make up around 45% of the human genome. A class of TEs, known as SINE-VNTR-Alu (SVA), demonstrate the capacity to mobilise throughout the genome, resulting in SVA polymorphisms for their presence or absence within the population. Although studies have previously highlighted the involvement of TEs within neurodegenerative diseases, such as Parkinson's disease and amyotrophic lateral sclerosis (ALS), the exact mechanism has yet to be identified. In this study, we used whole-genome sequencing and RNA sequencing data of ALS patients and healthy controls from the New York Genome Centre ALS Consortium to elucidate the influence of reference SVA elements on gene expressions genome-wide within central nervous system (CNS) tissues. To investigate this, we applied a matrix expression quantitative trait loci analysis and demonstrate that reference SVA insertion polymorphisms can significantly modulate the expression of numerous genes, preferentially in the trans position and in a tissue-specific manner. We also highlight that SVAs significantly regulate mitochondrial genes as well as genes within the HLA and MAPT loci, previously associated within neurodegenerative diseases. In conclusion, this study continues to bring to light the effects of polymorphic SVAs on gene regulation and further highlights the importance of TEs within disease pathology.

Item Type:	Article
Uncontrolled Keywords:	Central Nervous System, Humans, Amyotrophic Lateral Sclerosis, DNA Transposable Elements, Retroelements, Gene Expression, Minisatellite Repeats
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:	23 Apr 2024 08:37
Last Modified:	23 Apr 2024 08:38
DOI:	10.3390/biom14030358
Open Access URL:	https://doi.org/10.3390/biom14030358
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3180514