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Integrative genetic analysis of the amyotrophic lateral sclerosis spinal cord implicates glial activation and suggests new risk genes
medRxiv - Neurology Pub Date : 2021-09-02 , DOI: 10.1101/2021.08.31.21262682
Jack Humphrey , Sanan Venkatesh , Rahat Hasan , Jake T Herb , Katia de Paiva Lopes , Fahri Kucukali , Marta Byrska-Bishop , Uday S Evani , Giuseppe Narzisi , Delphine Fagegaltier , Kristel Sleegers , Hemali Phatnani , David A Knowles , Pietro Fratta , Towfique Raj ,

Amyotrophic lateral sclerosis (ALS) is a progressively fatal neurodegenerative disease affecting motor neurons in the brain and spinal cord. We used 380 post-mortem tissue RNA-seq transcriptomes from 154 ALS cases and 49 control individuals from cervical, thoracic, and lumbar spinal cord segments to investigate the gene expression response to ALS. We observed an increase in microglia and astrocyte expression, accompanied by a decrease in oligodendrocytes. By creating a gene co-expression network in the ALS samples, we identify several activated microglia modules that negatively correlate with retrospective disease duration.

中文翻译:

肌萎缩侧索硬化脊髓的综合遗传分析涉及神经胶质激活并提出新的风险基因

肌萎缩侧索硬化 (ALS) 是一种逐渐致命的神经退行性疾病,影响大脑和脊髓中的运动神经元。我们使用来自 154 个 ALS 病例和 49 个来自颈、胸和腰脊髓节段的对照个体的 380 个死后组织 RNA-seq 转录组来研究对 ALS 的基因表达反应。我们观察到小胶质细胞和星形胶质细胞表达增加,同时少突胶质细胞减少。通过在 ALS 样本中创建基因共表达网络,我们确定了几个与回顾性疾病持续时间呈负相关的激活小胶质细胞模块。
更新日期:2021-09-04
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