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Evaluation of Lupus Risk Variants for Their Potential Cis-Regulatory Effects on Long Non-coding RNA (LncRNA) Expression

Charfauros, Andrew-Jerome (2020) Evaluation of Lupus Risk Variants for Their Potential Cis-Regulatory Effects on Long Non-coding RNA (LncRNA) Expression. Master's Thesis, University of Pittsburgh. (Unpublished)

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Systemic Lupus Erythematosus (SLE) is a complex autoimmune disease (AID) that results from interactions between environmental and multiple genetic and epigenetic risk factors. Long non-coding RNAs (lncRNAs) are a class of non-protein-coding RNA molecules that execute multiple regulatory functions through their interactions with various (DNA, RNA, protein) molecules. Recent studies increasingly implicate lncRNAs as important regulators of immune response and autoimmunity. A growing body of evidence suggests an important role of non-coding regulatory variants in autoimmunity and recent multi-omics studies also implicate alterations in SNP‑lncRNA‑mRNA interactions as important contributors to AID onset and pathogenesis. While the aberrant expression of lncRNAs in SLE has recently been reported in multiple studies, only a few studies have proposed or established the potential involvement of GWAS-implicated lncRNAs in SLE. Given that most lncRNAs are relatively novel and only recently mapped to human genome, the SLE risk loci/variants warrant further exploration for their potential cis-regulatory effects on both mRNA and lncRNA expression, which is the main purpose of the current study. For this purpose, we performed in silico analyses of SLE associated loci/SNPs using the publicly available GTEx Portal (V8) in order to evaluate their cis-regulatory effects in SLE-relevant immune cells/tissues (LCLs and spleen). Our analyses have revealed a number of cis-regulated lncRNAs (known or novel) with potential roles in SLE-associated immunopathology, in addition to previously proposed protein-coding genes. Interestingly, the majority of significant SNP–lncRNA associations were observed in the spleen followed by LCLs, and only a small number of lncRNA genes were found to be cis-regulated in both spleen and LCLs. Our further in silico evaluations using additional bioinformatics tools and databases have revealed that highly SLE-relevant lncRNAs identified in this study were expressed in a wide spectrum of immune cell types (T cells, B cells, NK cells, monocytes), which is also in line with multiple adaptive and innate immune system abnormalities observed in SLE-related immunopathology. In summary, the results of our study provide further support to the recently proposed role of SNP‑lncRNA‑mRNA networks in immune regulation and autoimmunity. LncRNAs represent exciting pharmaceutical targets due to their ability to interact with a variety of molecules to regulate gene expression. Hence an improved understanding of their roles in SLE may guide future preventive or therapeutic interventions for this chronic autoimmune disease, which represents a significant public health concern due to significant morbidity and mortality.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Charfauros, Andrew-JeromeAMC320@pitt.eduAMC320
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee MemberLefterov, Iliyailiyal@pitt.eduiliyal
Committee MemberPark, Hyun Junghyp15@pitt.eduhyp15
Thesis AdvisorDemirci, Yesimfyd1@pitt.edufyd1
Date: 10 September 2020
Date Type: Publication
Defense Date: 14 August 2020
Approval Date: 10 September 2020
Submission Date: 27 July 2020
Access Restriction: 2 year -- Restrict access to University of Pittsburgh for a period of 2 years.
Number of Pages: 50
Institution: University of Pittsburgh
Schools and Programs: School of Public Health > Human Genetics
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: lupus, SLE, loci, polymorphism, SNP, lncRNA, eQTL
Date Deposited: 10 Sep 2020 22:23
Last Modified: 01 Sep 2022 05:15

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  • Evaluation of Lupus Risk Variants for Their Potential Cis-Regulatory Effects on Long Non-coding RNA (LncRNA) Expression. (deposited 10 Sep 2020 22:23) [Currently Displayed]


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