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

Abigail L. Pfaff; Vivien J. Bubb; John P. Quinn; Sulev Koks

doi:10.3390/ijms241411548

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

Journal article

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

Abigail L. Pfaff, Vivien J. Bubb, John P. Quinn and Sulev Koks

International journal of molecular sciences, Vol.24(14), 11548

2023

DOI: https://doi.org/10.3390/ijms241411548

PMID: 37511314

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Abstract

amyotrophic lateral sclerosis

exonisation

gene expression

retrotransposon

SINE-VNTR-Alu

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 HLA-A, 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.

Details

Title: A Genome-Wide Screen for the Exonisation of Reference SINE-VNTR-Alus and Their Expression in CNS Tissues of Individuals with Amyotrophic Lateral Sclerosis
Authors/Creators: Abigail L. Pfaff - Perron Institute for Neurological and Translational Science
Vivien J. Bubb - University of Liverpool
John P. Quinn - University of Liverpool
Sulev Koks - Murdoch University, Centre for Molecular Medicine and Innovative Therapeutics
Publication Details: International journal of molecular sciences, Vol.24(14), 11548
Publisher: MDPI
Grant note: MSWA and Perron Institute for Neurological and Translational Science
Identifiers: 991005595769407891
Murdoch Affiliation: Centre for Molecular Medicine and Innovative Therapeutics
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.54 Molecular & Cell Biology - Genetics; 1.54.1122 Transposable Elements
Web Of Science research areas: Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
ESI research areas: Chemistry