Abstract
The search for genetic variants that act as causative factors in human diseases by disrupting the normal splicing process has primarily focused on single nucleotide variants (SNVs). It is worth noting that insertions or deletions (indels) have also been sporadically reported as causative disease variants through their potential impact on the splicing process. In this study, to perform identification of indels inducing exon extension/shrinkage events, we used individual-specific genomes and RNA sequencing (RNA-seq) data pertaining to the corresponding individuals and identified 12 exon extension/shrinkage events that were potentially induced by indels that disrupted authentic splice sites or created novel splice sites in 235 normal individuals. By evaluating the impact of these abnormal splicing events on the resulting transcripts, we found that five events led to the generation of premature termination codons (PTCs), including those occurring within genes associated with genetic disorders. Our analysis revealed that the potential functions of indels have been underexamined, and it is worth considering the possibility that indels may affect splice site usage, using RNA-seq data to discover novel potentially disease-associated mutations.