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, Journal Year: 2025, Volume and Issue: 6(1), P. 1 - 1

Published: Jan. 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.

Language: Английский

scTCR-seq and HTS reveal a special novel TRBD2-TRBJ1 rearrangement in mammalian TRB CDR3 repertoire

BMC Genomics, Journal Year: 2025, Volume and Issue: 26(1)

Published: April 4, 2025

Mammalian T cell receptor (TCR) beta-chain (TRB) V-D-J rearrangement mainly follows the "12/23 rule", and "D-J preceding V-(D-J) rearrangement". Owing to physical position of D-J-C cluster in TRB locus, TRBD2 (D2) gene cannot directly perform inversional or deletional/loop-out with TRBJ1 (J1) gene. Our previous studies revealed a single reverse TRBV30 (TRBV31 mice) mammalian which can cause indirect D2 J1 gene; however, mechanism proportion involved germline are unknown. We obtained CDR3 repertoires thymus peripheral tissues from humans mice by HTS scTCR-seq found that 14% rearrangements is D2-J1 (D2-J2 account for approximately 86%). The V30 preferentially performs (V30-D2), leading V30-D2-J1 humans, D1 (V30-D1), allowing forward V genes (Vx) Vx-D2-J1 rearrangement. further were present more than 24% 15% rhesus monkeys bats, respectively. Moreover, bovine containing D1J1C1, D3J3C3, D2J2C2 clusters, 11% D3-J1 22% D2-J3 found. This study provides new perspective feasible solution research on significance special recombination pattern locus repertoire formed

Language: Английский