Determining whether the RNA isoforms from medically relevant genes have distinct functions could facilitate direct targeting of RNA isoforms for disease treatment. Here, as a step toward this goal for neurological diseases, we sequenced 12 postmortem, aged human frontal cortices (6 Alzheimer disease cases and 6 controls; 50% female) using one Oxford Nanopore PromethION flow cell per sample. We identified 1,917 medically relevant genes expressing multiple isoforms in the frontal cortex where 1,018 had multiple isoforms with different protein-coding sequences. Of these 1,018 genes, 57 are implicated in brain-related diseases including major depression, schizophrenia, Parkinson’s disease and Alzheimer disease. Our study also uncovered 53 new RNA isoforms in medically relevant genes, including several where the new isoform was one of the most highly expressed for that gene. We also reported on five mitochondrially encoded, spliced RNA isoforms. We found 99 differentially expressed RNA isoforms between cases with Alzheimer disease and controls.

确定来自医学相关基因的 RNA 同工型是否具有不同的功能可以促进直接靶向 RNA 同工型用于疾病治疗。在这里，作为实现神经系统疾病这一目标的一步，我们对每个样本使用一个 Oxford Nanopore PromethION 流动细胞对 12 个死后的老年人类额叶皮质（6 名阿尔茨海默病病例和 6 名对照；50% 女性）进行了测序。我们在额叶皮质中鉴定了 1,917 个表达多种亚型的医学相关基因，其中 1,018 个基因具有具有不同蛋白质编码序列的多种亚型。在这 1,018 个基因中，有 57 个与大脑相关疾病有关，包括重度抑郁症、精神分裂症、帕金森病和阿尔茨海默病。我们的研究还在医学相关基因中发现了 53 个新的 RNA 亚型，其中新亚型是该基因表达最高的几种亚型之一。我们还报道了五种线粒体编码的剪接 RNA 亚型。我们发现阿尔茨海默病病例和对照之间存在 99 种差异表达的 RNA 亚型。