Hughes, L.S.; Fröhlich, A.; Pfaff, A.L.; Bubb, V.J.; Quinn, J.P.; Kõks, S. Exploring SVA Insertion Polymorphisms in Shaping Differential Gene Expressions in the Central Nervous System. Biomolecules2024, 14, 358.
Hughes, L.S.; Fröhlich, A.; Pfaff, A.L.; Bubb, V.J.; Quinn, J.P.; Kõks, S. Exploring SVA Insertion Polymorphisms in Shaping Differential Gene Expressions in the Central Nervous System. Biomolecules 2024, 14, 358.
Hughes, L.S.; Fröhlich, A.; Pfaff, A.L.; Bubb, V.J.; Quinn, J.P.; Kõks, S. Exploring SVA Insertion Polymorphisms in Shaping Differential Gene Expressions in the Central Nervous System. Biomolecules2024, 14, 358.
Hughes, L.S.; Fröhlich, A.; Pfaff, A.L.; Bubb, V.J.; Quinn, J.P.; Kõks, S. Exploring SVA Insertion Polymorphisms in Shaping Differential Gene Expressions in the Central Nervous System. Biomolecules 2024, 14, 358.
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 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), however 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 Center ALS Consortium, to elucidate the influence of reference SVA elements on gene expression genome-wide within central nervous system (CNS) tissues. To investigate this, we applied matrix expression quantitative trait loci analysis and demonstrated 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 disease. 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.
Medicine and Pharmacology, Pathology and Pathobiology
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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