TY - JOUR AU - AU - Hatje, Klas AU - Rahman, Raza-Ur AU - Vidal, Ramon O. AU - Simm, Dominic AU - Hammesfahr, Björn AU - Bansal, Vikas AU - Rajput, Ashish AU - Mickael, Michel Edwar AU - Sun, Ting AU - Bonn, Stefan AU - Kollmar, Martin T1 - The landscape of human mutually exclusive splicing PY - 2017 N2 - Mutually exclusive splicing of exons is a mechanism of functional gene and protein diversification with pivotal roles in organismal development and diseases such as Timothy syndrome, cardiomyopathy and cancer in humans. In order to obtain a first genomewide estimate of the extent and biological role of mutually exclusive splicing in humans, we predicted and subsequently validated mutually exclusive exons (MXEs) using 515 publically available RNA-Seq datasets. Here, we provide evidence for the expression of over 855 MXEs, 42% of which represent novel exons, increasing the annotated human mutually exclusive exome more than fivefold. The data provide strong evidence for the existence of large and multi-cluster MXEs in higher vertebrates and offer new insights into MXE evolution. More than 82% of the MXE clusters are conserved in mammals, and five clusters have homologous clusters in Drosophila Finally, MXEs are significantly enriched in pathogenic mutations and their spatio-temporal expression might predict human disease pathology. DO - doi:10.15252/msb.20177728 LA - en ER -