与阿尔茨海默病相关的位点特异性内源性逆转录病毒表达
Locus specific endogenous retroviral expression associated with Alzheimer's disease.
作者信息
Dawson Tyson, Rentia Uzma, Sanford Jessie, Cruchaga Carlos, Kauwe John S K, Crandall Keith A
机构信息
Computational Biology Institute, The George Washington University, Washington, DC, United States.
Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, The George Washington University, Washington, DC, United States.
出版信息
Front Aging Neurosci. 2023 Jul 6;15:1186470. doi: 10.3389/fnagi.2023.1186470. eCollection 2023.
INTRODUCTION
Human endogenous retroviruses (HERVs) are transcriptionally-active remnants of ancient retroviral infections that may play a role in Alzheimer's disease.
METHODS
We combined two, publicly available RNA-Seq datasets with a third, novel dataset for a total cohort of 103 patients with Alzheimer's disease and 45 healthy controls. We use telescope to perform HERV quantification for these samples and simultaneously perform gene expression analysis.
RESULTS
We identify differentially expressed genes and differentially expressed HERVs in Alzheimer's disease patients. Differentially expressed HERVs are scattered throughout the genome; many of them are members of the HERV-K superfamily. A number of HERVs are correlated with the expression of dysregulated genes in Alzheimer's and are physically proximal to genes which drive disease pathways.
DISCUSSION
Dysregulated expression of ancient retroviral insertions in the human genome are present in Alzheimer's disease and show localization patterns that may explain how these elements drive pathogenic gene expression.
引言
人类内源性逆转录病毒（HERV）是古代逆转录病毒感染的转录活性残余物，可能在阿尔茨海默病中发挥作用。
方法
我们将两个公开可用的RNA测序数据集与第三个新数据集相结合，形成了一个由103名阿尔茨海默病患者和45名健康对照组成的总队列。我们使用望远镜对这些样本进行HERV定量，并同时进行基因表达分析。
结果
我们在阿尔茨海默病患者中鉴定出差异表达基因和差异表达的HERV。差异表达的HERV散布在整个基因组中；其中许多是HERV-K超家族的成员。一些HERV与阿尔茨海默病中失调基因的表达相关，并且在物理上靠近驱动疾病途径的基因。
讨论
人类基因组中古代逆转录病毒插入的失调表达存在于阿尔茨海默病中，并显示出可能解释这些元件如何驱动致病基因表达的定位模式。
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