Genetics of cell-type-specific post-transcriptional gene regulation during human neurogenesis,American Journal of Human Genetics

当前位置： X-MOL 学术 › Am. J. Hum. Genet. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Genetics of cell-type-specific post-transcriptional gene regulation during human neurogenesis
American Journal of Human Genetics ( IF 8.1 ) Pub Date : 2024-08-20 , DOI: 10.1016/j.ajhg.2024.07.015
Nil Aygün ₁ , Celine Vuong ₂ , Oleh Krupa ₁ , Jessica Mory ₁ , Brandon D Le ₁ , Jordan M Valone ₁ , Dan Liang ₁ , Beck Shafie ₂ , Pan Zhang ₂ , Angelo Salinda ₂ , Cindy Wen ₂ , Michael J Gandal ₃ , Michael I Love ₄ , Luis de la Torre-Ubieta ₂ , Jason L Stein ₁

Affiliation

Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; UNC Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Intellectual and Developmental Disabilities Research Center, Semel Institute, David Geffen School of Medicine University of California, Los Angeles, Los Angeles, CA 90095, USA; Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Psychiatry and Biobehavioral Sciences, Semel Institute, David Geffen School of Medicine University of California, Los Angeles, Los Angeles, CA 90095, USA.
Intellectual and Developmental Disabilities Research Center, Semel Institute, David Geffen School of Medicine University of California, Los Angeles, Los Angeles, CA 90095, USA; Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Psychiatry and Biobehavioral Sciences, Semel Institute, David Geffen School of Medicine University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

The function of some genetic variants associated with brain-relevant traits has been explained through colocalization with expression quantitative trait loci (eQTL) conducted in bulk postmortem adult brain tissue. However, many brain-trait associated loci have unknown cellular or molecular function. These genetic variants may exert context-specific function on different molecular phenotypes including post-transcriptional changes. Here, we identified genetic regulation of RNA editing and alternative polyadenylation (APA) within a cell-type-specific population of human neural progenitors and neurons. More RNA editing and isoforms utilizing longer polyadenylation sequences were observed in neurons, likely due to higher expression of genes encoding the proteins mediating these post-transcriptional events. We also detected hundreds of cell-type-specific editing quantitative trait loci (edQTLs) and alternative polyadenylation QTLs (apaQTLs). We found colocalizations of a neuron edQTL in CCDC88A with educational attainment and a progenitor apaQTL in EP300 with schizophrenia, suggesting that genetically mediated post-transcriptional regulation during brain development leads to differences in brain function.

更新日期：2024-08-20

点击分享查看原文

点击收藏

公开下载

阅读更多本刊新发论文本刊介绍/投稿指南