Fig 1: 1H6 peaks are enriched at key regulatory elements of neuronal genes.a Venn diagram and Gene Ontology analysis of genes associated with peaks common to both Ctrl2 and AD1 neurons or specific to AD neurons (AD1). The most significant pathways are indicated on the diagram along with the respective P value calculated by the GO algorithm. b Sashimi plot of three different loci containing a 1H6 peak and associated with a differential splicing event. Exons are represented as blue boxes. The red lines represent a peak found in AD neurons; the green lines represent a peak found in control (Ctrl) neurons green. Loss of the intragenic peak in AD neurons between the SMN1 and NAIP genes is associated with the formation of cryptic fusion transcripts. The common peak found at the APP locus (but increased in AD) is associated with loss of some minor isoforms in AD neurons. The unique peak gained in AD neurons at the DNAH6 locus is associated with loss of minor isoforms and a large splicing gap in AD neurons. c Table showing the number of genes containing a 1H6 peak, as well as the number of genes that entailed a differential splicing event associated with a 1H6 peak when comparing Ctrl1 and Ctrl2 neurons with AD1 neurons. The splicing events were subdivided into loss of a minor isoform or formation of a gap junction. d Western blot analyses of Ctrl2 and AD2 neurons. GAPDH and ponceau were used as normalizers. Black arrows indicate differentially expressed protein variants. e Volcano plot showing differential gene expression between control (Ctrl1 and Ctrl2 combined) and AD1 neurons using RNA-seq. Superimposed in red are genes containing a G4 peak and associated with an abnormal splicing event. Note that genes in the third volcano plot (i.e., gained in AD) are significantly downregulated, and genes in the first volcano plot (i.e., lost in AD) are significantly upregulated in AD1. For each gene distribution (red dotted ovals), a P value was calculated using binomial distribution, knowing that 51% of the genes were upregulated.