IMR Press / FBS / Volume 16 / Issue 1 / DOI: 10.31083/j.fbs1601004
Open Access Review
Decoding Non-coding Variants: Recent Approaches to Studying Their Role in Gene Regulation and Human Diseases
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1 Department of Biology, University of Puerto Rico-Río Piedras, 00931 San Juan, Puerto Rico
*Correspondence: (Edwin G. Peña-Martínez); jose.rodrí (José A. Rodríguez-Martínez)
Front. Biosci. (Schol Ed) 2024, 16(1), 4;
Submitted: 16 October 2023 | Revised: 23 December 2023 | Accepted: 2 January 2024 | Published: 1 March 2024
Copyright: © 2024 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.

Genome-wide association studies (GWAS) have mapped over 90% of disease- and quantitative-trait-associated variants within the non-coding genome. Non-coding regulatory DNA (e.g., promoters and enhancers) and RNA (e.g., 5 and 3 UTRs and splice sites) are essential in regulating temporal and tissue-specific gene expressions. Non-coding variants can potentially impact the phenotype of an organism by altering the molecular recognition of the cis-regulatory elements, leading to gene dysregulation. However, determining causality between non-coding variants, gene regulation, and human disease has remained challenging. Experimental and computational methods have been developed to understand the molecular mechanism involved in non-coding variant interference at the transcriptional and post-transcriptional levels. This review discusses recent approaches to evaluating disease-associated single-nucleotide variants (SNVs) and determines their impact on transcription factor (TF) binding, gene expression, chromatin conformation, post-transcriptional regulation, and translation.

non-coding variants
gene regulation
transcription factors
massively parallel reporter assay
RNA processing
Graphical Abstract
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5R25GM061151-20/NIH RISE Fellowship
STC-1231306/NSF BioXFEL Fellowship
Fig. 1.
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