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Page 214 Bergara-Muguruza et al. J Transl Genet Genom 2023;7:213-229 https://dx.doi.org/10.20517/jtgg.2023.14

development of different immune-related diseases and highlight the potential of these molecules in the
development of emerging RNA-based therapies.

Keywords: lncRNA, SNP, immune-related diseases, RNA-based therapies

INTRODUCTION
The development of next-generation sequencing (NGS) techniques has revolutionized the study of
biological systems, allowing researchers to sequence entire genomes at an unprecedented speed and scale.
These technological advances have presented NGS as an essential tool both in basic and translational
[1]
research , enabling a wide range of scientific applications. NGS, together with recent developments in
annotation methods and computational programming , have played a critical role in the identification of
[2]
[2]
risk alleles associated with complex diseases through genome-wide association studies (GWAS) . In
addition, several high-throughput array-based approaches, such as the Immunochip microarray, have
facilitated the analysis of large numbers of single-nucleotide polymorphisms (SNPs) in immune-related
[3,4]
loci .

This genetic mapping has yielded valuable insights into complex diseases, including the identification of
immune disease-conferring gene variants that can help in risk prediction. More importantly, this knowledge
has guided towards the understanding of the underlying biological mechanisms in these complex diseases ,
[5]
which has presented new possible strategies for prevention, diagnosis, and therapeutics. However, this
knowledge has remained limited so far, primarily because around 90% of the SNPs identified through
[6]
GWAS are located in non-coding regions, evenly distributed between intergenic and intronic sequences ,
making it challenging to establish the precise biological functions associated with these variants .
[7]

Recent studies have shown that disease-associated SNPs are enriched in long non-coding RNAs
[8]
(lncRNAs) . lncRNAs are a diverse group of non-coding RNAs of more than 200 nucleotides in length [9,10] ;
their expression is rather cell type-specific in comparison to that of protein-coding genes, and they appear
to be predominantly localized in the nucleus . To date, lncRNAs have been implicated in nearly all stages
[11]
of the gene life cycle, encompassing transcription, mRNA splicing, RNA decay and translation. Given the
broad expression of lncRNAs and their participation in fundamental cellular processes, their potential
association with various disorders has been explored, particularly in complex diseases, where the signals of
[12]
association frequently originate from non-coding regions of the genome . Interestingly, increasing studies
confirm that the presence of SNPs within lncRNAs can influence diverse aspects of their biogenesis [13,14] , and
these molecules have shown to be valuable disease-specific biomarkers as well as potential targets for future
personalized therapeutic approaches [15,16] .

In this review, the implication of immune disease-associated SNPs located in lncRNAs has been studied
[Table 1], highlighting the importance of the identification and the functional characterization of these
molecules in the context of autoimmune and immune-related disorders (AIDs) to find possible biomarkers
and/or therapeutic targets.

GENE REGULATION BY lncRNAs
lncRNAs were initially believed to lack coding capacity and were considered transcriptional by-products or
"junk" . However, consortiums such as ENCODE (The Encyclopedia of DNA Elements) and FANTOM
[17]
[2]
(The Functional Annotation of the Mammalian Genome) , together with the development of new high
throughput sequencing technologies, revealed the presence of an extensive set of non-coding elements with