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

Journal of Molecular Pathology, Год журнала: 2025, Номер 6(1), С. 1 - 1

Опубликована: Янв. 6, 2025

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) Human Leucocyte Antigen (HLA) class I genotypes PD. In this study, aimed to evaluate SVA their regulatory effects transposable element (TE) transcription MHC region. Methods: Transcriptome data from peripheral blood cells 1530 individuals Progression Markers Initiative (PPMI) cohort were reanalyzed for TE gene using publicly available bioinformatics tools, including Salmon Matrix-eQTL. Results: Four structurally SVAs regulated 18 distinct clusters 235 loci, comprising LINEs (33%), SINEs (19%), LTRs (35%), ancient transposon DNA elements (12%) near HLA genes. transcribed TEs predominantly short, an average length 445 nucleotides. these varied significantly terms types, numbers, transcriptional activation or repression. SVA-regulated RNAs appear function as enhancer-like elements, differentially influencing genes, non-HLA noncoding RNAs. Conclusions: These findings highlight roles associated complex networks governing coding potential implications immune susceptibility.

Язык: Английский

SVA Regulation of Transposable Element Clustered Transcription within the Major Histocompatibility Complex Genomic Class II Region of the Parkinson’s Progression Markers Initiative

Genes, Год журнала: 2024, Номер 15(9), С. 1185 - 1185

Опубликована: Сен. 9, 2024

SINE-VNTR-Alu (SVA) retrotransposons can regulate expression quantitative trait loci (eQTL) of coding and noncoding genes including transposable elements (TEs) distributed throughout the human genome. Previously, we reported that expressed SVAs leucocyte antigen (HLA) class II genotypes on chromosome 6 were associated significantly with Parkinson’s disease (PD). Here, our aim was to follow-up previous study evaluate SVA associations their regulatory effects transcription TEs within HLA genomic region. We reanalyzed transcriptome data peripheral blood cells from Progression Markers Initiative (PPMI) for 1530 subjects TE gene RNAs publicly available computing packages. Four structurally polymorphic 20 distinct clusters 235 represented by LINES (37%), SINES (28%), LTR/ERVs (23%), ancient transposon DNA (12%) are located in close proximity genes. The transcribed mostly short length, an average size 389 nucleotides. numbers, types profiles positive negative regulation varied markedly between four SVAs. appear be enhancer-like coordinated differentially Future work mechanisms underlying potential impact is essential elucidating roles normal cellular processes pathogenesis.

Язык: Английский