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帕金森病中的基因表达不对称性;α-突触核蛋白和β-突触核蛋白基因表达水平的变化与半球特异性严重程度相关。

Gene expression asymmetry in Parkinson's Disease; variation of and gene expression levels are correlated with hemisphere specific severity.

作者信息

Pierce Steven E, van der Schans Edwin J C, Ensink Elizabeth, Coetzee Gerhard A

机构信息

Van Andel Institute, Grand Rapids, Michigan, USA.

出版信息

bioRxiv. 2024 Jul 4:2024.07.02.601704. doi: 10.1101/2024.07.02.601704.

DOI:10.1101/2024.07.02.601704
PMID:39005359
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11245011/
Abstract

Parkinson's Disease (PD) develops unilaterally, which may be related to brain hemispheric differences in gene expression. Here we measured bulk RNA-seq levels in neuronal nuclei obtained from prefrontal cortex postmortem brain samples from males and females with PD and from healthy controls. Left and right hemispheres from each brain were related the side of symptom onset and compared. We employed two approaches; first we identified genes differentially expressed between PD and controls and between left vs right PD brain hemispheres. Second, we examined the presence of, and correlates to, variable asymmetry seen in candidate PD differentially expressed genes. We found large variation among individuals with PD, and PD stratification by gene expression similarity was required for patterns of genetic asymmetry to emerge. For a subset of PD brains, hemispherical variation of and gene levels correlated with the side of PD symptom onset.

摘要

帕金森病(PD)单侧发病,这可能与大脑半球基因表达差异有关。在此,我们测量了从患有PD的男性和女性以及健康对照者的前额叶皮质死后脑样本中获取的神经元细胞核中的整体RNA测序水平。将每个大脑的左右半球与症状发作侧相关联并进行比较。我们采用了两种方法:首先,我们鉴定了PD与对照之间以及PD脑的左右半球之间差异表达的基因。其次,我们检查了候选PD差异表达基因中可变不对称性的存在及其相关性。我们发现PD患者个体之间存在很大差异,并且需要通过基因表达相似性对PD进行分层才能出现遗传不对称模式。对于一部分PD大脑,[此处原文可能缺失具体基因名称]基因水平的半球差异与PD症状发作侧相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adb7/11245011/cda2552604f4/nihpp-2024.07.02.601704v1-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adb7/11245011/0832b2fc18e6/nihpp-2024.07.02.601704v1-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adb7/11245011/d38d99e057fa/nihpp-2024.07.02.601704v1-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adb7/11245011/cda2552604f4/nihpp-2024.07.02.601704v1-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adb7/11245011/0832b2fc18e6/nihpp-2024.07.02.601704v1-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adb7/11245011/d38d99e057fa/nihpp-2024.07.02.601704v1-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adb7/11245011/cda2552604f4/nihpp-2024.07.02.601704v1-f0003.jpg

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