Examining Pathogenesis in Genome Instability Associated Neurodegenerative Mouse Model [polyA-RNA-seq]

DNA damage can promote altered RNA splicing and decreased gene expression (Gregersen and Svejstrup, 2018; Milek et al., 2017; Munoz et al., 2009; Shkreta and Chabot, 2015), and aberrant splicing is implicated in neurodegenerative diseases including amyotrophic lateral sclerosis (ALS), Fragile X syndrome and spinal muscular atrophy (SMA) (Conlon et al., 2016; Jia et al., 2012; Loomis et al., 2014; Qiu et al., 2014; Scotti and Swanson, 2016). Therefore, we used RNA-seq data to assess RNA-splicing in double-mutant brain tissue using multivariate analysis of transcriptional splicing (rMATS) (Shen et al., 2014) and a splicing deficiency score algorithm (Bai et al., 2013) to assess intron retention. Overall design: PolyA-enriched RNA sequencing of the cerebellum and cortex examining splicing deficiencies in ATM APTX null and ATM PARP null brains.