The Transcription of Transposable Elements Differentially Regulated by SVAs in the Major Histocompatibility Complex Class I Region of a Parkinson’s Progression Markers Initiative Cohort

Background/Objectives: The highly polymorphic Major Histocompatibility Complex (MHC) genomic region, located on the short arm of chromosome 6, is implicated genetically in Parkinson’s disease (PD), a progressive neurodegenerative disorder with motor and non-motor symptoms. Previously, we reported significant associations between SINE-VNTR-Alu (SVA) expression quantitative trait loci (eQTLs) and Human Leucocyte Antigen (HLA) class I genotypes in PD. In this study, we aimed to evaluate SVA associations and their regulatory effects on transposable element (TE) transcription in the MHC class I region. Methods: Transcriptome data from the peripheral blood cells of 1530 individuals in the Parkinson’s Progression Markers Initiative (PPMI) cohort were reanalyzed for TE and gene expression using publicly available bioinformatics tools, including Salmon and Matrix-eQTL. Results: Four structurally polymorphic SVAs regulated the transcription of 18 distinct clusters of 235 TE loci, comprising LINEs (33%), SINEs (19%), LTRs (35%), and ancient transposon DNA elements (12%) located near HLA genes. The transcribed TEs were predominantly short, with an average length of 445 nucleotides. The regulatory effects of these SVAs varied significantly in terms of TE types, numbers, and transcriptional activation or repression. The SVA-regulated TE RNAs in blood cells appear to function as enhancer-like elements, differentially influencing the expression of HLA class I genes, non-HLA genes, and noncoding RNAs. Conclusions: These findings highlight the roles of SVAs and their associated TEs in the complex regulatory networks governing coding and noncoding gene expression in the MHC class I region, with potential implications for immune function and disease susceptibility.