Genomic and transcriptomic studies of expression quantitative trait loci (eQTL) revealed that SINE-VNTR-Alu (SVA) retrotransposon insertion polymorphisms (RIPs) within human genomes markedly affect the co-expression of many coding and noncoding genes by coordinated regulatory processes. This study examined the polymorphic SVA modulation of gene co-expression within the major histocompatibility complex (MHC) genomic region where more than 160 coding genes are involved in innate and adaptive immunity. We characterized the modulation of SVA RIPs utilizing the genomic and transcriptomic sequencing data obtained from whole blood of 1266 individuals in the Parkinson's Progression Markers Initiative (PPMI) cohort that included an analysis of human leukocyte antigen (HLA)-A regulation in a subpopulation of the cohort. The regulatory properties of eight SVAs located within the class I and class II MHC regions were associated with differential co-expression of 71 different genes within and 75 genes outside the MHC region. Some of the same genes were affected by two or more different SVA. Five SVA are annotated in the human genomic reference sequence GRCh38.p14/hg38, whereas the other three were novel insertions within individuals. We also examined and found distinct structural effects (long and short variants and the CT internal variants) for one of the SVA (R_SVA_24) insertions on the differential expression of the HLA-A gene within a subpopulation (550 individuals) of the PPMI cohort. This is the first time that many HLA and non-HLA genes (multilocus expression units) and splicing mechanisms have been shown to be regulated by eight structurally polymorphic SVA within the MHC genomic region by applying precise statistical analysis of RNA data derived from the blood samples of a human cohort population. This study shows that SVA within the MHC region are important regulators or rheostats of gene co-expression that might have potential roles in diversity, health, and disease.

中文翻译：

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主要组织相容性复合体中 SVA 逆转录转座子对表达数量性状位点的调节。

表达数量性状位点（eQTL）的基因组和转录组研究表明，人类基因组中的SINE-VNTR-Alu（SVA）逆转录转座子插入多态性（RIP）通过协调的调控过程显着影响许多编码和非编码基因的共表达。这项研究检查了主要组织相容性复合体 (MHC) 基因组区域内基因共表达的多态性 SVA 调节，该区域有超过 160 个编码基因参与先天性和适应性免疫。我们利用从帕金森病进展标记计划 (PPMI) 队列中 1266 名个体的全血获得的基因组和转录组测序数据来表征 SVA RIP 的调节，其中包括对帕金森病进展标记物亚群中人类白细胞抗原 (HLA)-A 调节的分析。队列。位于 I 类和 II 类 MHC 区域内的 8 个 SVA 的调控特性与 MHC 区域内 71 个不同基因和 MHC 区域外 75 个不同基因的差异共表达相关。一些相同的基因受到两种或多种不同SVA的影响。人类基因组参考序列 GRCh38.p14/hg38 中注释了五个 SVA，而其他三个是个体内的新插入。我们还检查并发现了 SVA (R_SVA_24) 插入之一对 PPMI 队列亚群（550 人）内 HLA-A 基因差异表达的明显结构影响（长和短变异以及 CT 内部变异）。通过对血液样本中的 RNA 数据进行精确统计分析，首次发现许多 HLA 和非 HLA 基因（多位点表达单位）和剪接机制受到 MHC 基因组区域内八个结构多态性 SVA 的调节人类队列人口。这项研究表明，MHC 区域内的 SVA 是基因共表达的重要调节剂或变阻器，可能在多样性、健康和疾病中发挥潜在作用。