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阿尔茨海默病患者大脑中的全转录组piRNA分析

Transcriptome-wide piRNA profiling in human brains of Alzheimer's disease.

作者信息

Qiu Wenying, Guo Xiaoyun, Lin Xiandong, Yang Qian, Zhang Wanying, Zhang Yong, Zuo Lingjun, Zhu Yong, Li Chiang-Shan R, Ma Chao, Luo Xingguang

机构信息

Department of Human Anatomy, Histology and Embryology, Institute of Basic Medical Sciences, Neuroscience Center, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China.

Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA; Shanghai Mental Health Center, Shanghai, China.

出版信息

Neurobiol Aging. 2017 Sep;57:170-177. doi: 10.1016/j.neurobiolaging.2017.05.020. Epub 2017 Jun 3.

Abstract

Discovered in the brains of multiple animal species, piRNAs may contribute to the pathogenesis of neuropsychiatric illnesses. The present study aimed to identify brain piRNAs across transcriptome that are associated with Alzheimer's disease (AD). Prefrontal cortical tissues of 6 AD cases and 6 controls were examined for piRNA expression levels using an Arraystar HG19 piRNA array (containing 23,677 piRNAs) and genotyped for 17 genome-wide significant and replicated risk SNPs. We examined whether piRNAs are expressed differently between AD cases and controls and explored the potential regulatory effects of risk SNPs on piRNA expression levels. We identified a total of 9453 piRNAs in human brains, with 103 nominally (p < 0.05) differentially (>1.5 fold) expressed in AD cases versus controls and most of the 103 piRNAs nominally correlated with genome-wide significant risk SNPs. We conclude that piRNAs are abundant in human brains and may represent risk biomarkers of AD.

摘要

在多种动物物种的大脑中发现的piRNA可能与神经精神疾病的发病机制有关。本研究旨在鉴定转录组中与阿尔茨海默病(AD)相关的脑piRNA。使用Arraystar HG19 piRNA阵列(包含23,677个piRNA)检测6例AD病例和6例对照的前额叶皮质组织中piRNA的表达水平,并对17个全基因组显著且重复的风险单核苷酸多态性(SNP)进行基因分型。我们研究了AD病例和对照之间piRNA的表达是否存在差异,并探讨了风险SNP对piRNA表达水平的潜在调控作用。我们在人类大脑中总共鉴定出9453个piRNA,其中103个在AD病例与对照中名义上(p < 0.05)差异表达(>1.5倍),并且这103个piRNA中的大多数名义上与全基因组显著的风险SNP相关。我们得出结论,piRNA在人类大脑中丰富存在,可能代表AD的风险生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f304/5542056/395fc32a457c/nihms881704f1.jpg

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