Evidence of Extensive Alternative Splicing in Post Mortem Human Brain HTT Transcription by mRNA Sequencing.

Despite 20 years since its discovery, the gene responsible for Huntington’s Disease, HTT, has still not had its function or transcriptional profile completely characterized. In response to a recent report by Ruzo et al. of several novel splice forms of HTT in human embryonic stem cell lines, we have analyzed a set of mRNA sequencing datasets from post mortem human brain from Huntington’s disease, Parkinson’s disease, and neurologically normal control subjects to evaluate support for previously observed and to identify novel splice patterns. A custom analysis pipeline produced supporting evidence for some of the results reported by two previous studies of alternative isoforms as well as identifying previously unreported splice patterns. All of the alternative splice patterns were of relatively low abundance compared to the canonical splice form.

尽管自发现以来已经过去了20年，但导致亨廷顿病的基因HTT，其功能或转录图谱仍未得到完全表征。针对Ruzo等人最近在人类胚胎干细胞系中发现几种新型HTT剪接形式的报告，我们分析了一组来自亨廷顿病、帕金森病和神经正常对照受试者的死后人类大脑的mRNA测序数据集，以评估对先前观察结果的支持，并识别新的剪接模式。一个定制的分析流程为先前两项关于可变异构体的研究报告的一些结果提供了支持证据，同时也识别出了先前未报道的剪接模式。与标准剪接形式相比，所有可变剪接模式的丰度都相对较低。