Figure 3.

New TE clusters as substrates for aberrant splice site activation. (a,b) Mutation-induced exonization of the LTR78-AluJ cluster in F8 intron 18. (a) Schematics of mutation-induced pseudoexon splice sites located in separate TEs. Canonical exons are denoted by black boxes, pseudoexon by a grey box. Exon length is in nucleotides below. A scale at the bottom is in kilobases (kb). Mutation (asterisk) activated the pseudoexon via a de novo 5’ss, leading to mild haemophilia A [62]. Dotted lines above and below the pre-mRNA indicate aberrant and canonical splicing, respectively. (b) Sequences around pseudoexon splice sites. Splice sites are denoted by a slash. A putative branch point adenine in LTR78 (boxed) was predicted by the SVM-BP algorithm [73]; the disease-causing mutation is underlined. Sequences in blue and red are derived from LTR78 and AluJ, respectively. (c,d) Mutation-induced exonization of a LINE and MER58A cluster in COL4A5. (c) Schematics of mutation-induced splice sites activated in separate TEs. For full legend, see panel (a). (d) Sequences around pseudoexon splice sites. Sequences in blue are derived from a LINE-1 copy, sequences in orange from a MER58A copy. Mutation (asterisk) creating the 3’ss AG led to pseudoexon activation, causing Alport syndrome [63]