Background: Systemic lupus erythematosus (SLE) is a complex autoimmune disease, which mainly affects childbearing-aged women. Although its pathogenesis is not fully clear yet, studies have shown that genetic factors are vital in exploring SLE pathogenic mechanisms.
Objective: The purpose of this study is to predict and screen potential pathogenic single nucleotide polymorphisms (SNPs). By comparing the genomes of members of a family with SLE and performing functional analysis on mutation loci, possible pathogenic polymorphisms are screened. These analyses lay the foundation for the further mechanism research.
Method: Genomic alignment, variant calling and functional annotation were performed and then ~92,778 original SNPs were obtained for each specimen. We found the patient/healthy-specific SNPs show different conservative score distribution. Many patient-specific SNPs were detected in SLE-related pathways. We therefore investigated the patient-specific SNPs from four diverse perspectives, including nonsynonymous variations in exon regions, expression quantitative trait loci (eQTLs), RNA binding sites and RNA-binding protein (RBP) binding sites.
Results: 18 potential pathogenic SNPs were identified in SLE risk genes, which were associated with functional loci. Systematic literature study was then performed to verify these potential pathogenic SNPs.
Conclusion: This study could help to better explain possible genetic mechanisms of SLE from the perspective of variation. It could provide effective strategy for the accurate diagnosis and personalized treatment of SLE patients.