A Genome-Wide Screen for the Exonisation of Reference SINE-VNTR-Alus and Their Expression in CNS Tissues of Individuals with Amyotrophic Lateral Sclerosis

Pfaff, Abigail L, Bubb, Vivien J ORCID: 0000-0003-2763-7004, Quinn, John P ORCID: 0000-0003-3551-7803 and Koks, Sulev ORCID: 0000-0001-6087-6643 (2023) A Genome-Wide Screen for the Exonisation of Reference SINE-VNTR-Alus and Their Expression in CNS Tissues of Individuals with Amyotrophic Lateral Sclerosis. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 24 (14). 11548-.

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Official URL: http://dx.doi.org/10.3390/ijms241411548

Abstract

The hominid-specific retrotransposon SINE-VNTR-Alu (SVA) is a composite element that has contributed to the genetic variation between individuals and influenced genomic structure and function. SVAs are involved in modulating gene expression and splicing patterns, altering mRNA levels and sequences, and have been associated with the development of disease. We evaluated the genome-wide effects of SVAs present in the reference genome on transcript sequence and expression in the CNS of individuals with and without the neurodegenerative disorder Amyotrophic Lateral Sclerosis (ALS). This study identified SVAs in the exons of 179 known transcripts, several of which were expressed in a tissue-specific manner, as well as 92 novel exonisation events occurring in the motor cortex. An analysis of 65 reference genome SVAs polymorphic for their presence/absence in the ALS consortium cohort did not identify any elements that were significantly associated with disease status, age at onset, and survival. However, there were transcripts, such as transferrin and <i>HLA-A</i>, that were differentially expressed between those with or without disease, and expression levels were associated with the genotype of proximal SVAs. This study demonstrates the functional consequences of several SVA elements altering mRNA splicing patterns and expression levels in tissues of the CNS.

Item Type:	Article
Uncontrolled Keywords:	amyotrophic lateral sclerosis, exonisation, gene expression, retrotransposon, SINE-VNTR-Alu
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:	28 Sep 2023 10:21
Last Modified:	28 Sep 2023 10:22
DOI:	10.3390/ijms241411548
Open Access URL:	https://doi.org/10.3390/ijms241411548
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3173157