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.
Department of Neurology, Boston University School of Medicine, Boston, Massachusetts, United States of America; Bioinformatics Program, Boston University, Boston, Massachusetts, United States of America.
Adam T
AT
Labadorf
Department of Neurology, Boston University School of Medicine, Boston, Massachusetts, United States of America; Bioinformatics Program, Boston University, Boston, Massachusetts, United States of America; Genome Science Institute, Boston University School of Medicine, Boston, Massachusetts, United States of America.
Richard H
RH
Myers
D017398:Alternative Splicing; D001921:Brain / Q000378:metabolism*; D016022:Case-Control Studies; D005091:Exons; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017423:Sequence Analysis, RNA; D014158:Transcription, Genetic
C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger