Ribo-depleted RNA-Seq Libraries From Huntington's Disease Brain

Transcriptional dysregulation is well documented in Huntington’s disease (HD) post-mortem brain. We previously identified gene expression profiles from both symptomatic and asymptomatic HD prefrontal cortex which characterize the effects of degeneration in disease versus normal brains. Transcriptional dysregulation in HD brain is well documented by these studies and others, but the extent and causes of this dysregulation remain unknown. Here, we present a large ribo-depleted RNA sequencing (rdRNA-Seq) dataset and novel bioinformatic methodology to further characterize transcriptional dysregulation in HD brain as it relates to disease variables, including CAG repeat size, age of symptom onset, and rate of neurodegeneration. rdRNA-Seq was performed in 98 post-mortem HD prefrontal cortex samples previously characterized for CAG repeat size and extent of striatal and cortical involvement. rdRNA-Seq data, in contrast to poly-A selected RNA-Seq, allows the assessment of transcribed non-coding genomic regions that may correspond to large-scale regulatory mechanisms as well as individual genes. Unlike traditional RNA-Seq analysis, which focuses almost exclusively on annotated regions of the genome, we developed a novel bioinformatic method that divides the genome into bins and identifies genomic loci of arbitrary length associated with variables of interest.