PT  - JOURNAL ARTICLE
AU  - Klas Hatje
AU  - Ramon O. Vidal
AU  - Raza-Ur Rahman
AU  - Dominic Simm
AU  - Björn Hammesfahr
AU  - Orr Shomroni
AU  - Stefan Bonn
AU  - Martin Kollmar
TI  - The landscape of human mutually exclusive splicing
AID  - 10.1101/133215
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 133215
4099  - http://biorxiv.org/content/early/2017/05/02/133215.short
4100  - http://biorxiv.org/content/early/2017/05/02/133215.full
AB  - 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 genome-wide 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 five-fold. The data provides strong evidence for the existence of large and multi-cluster MXEs in higher vertebrates and offers new insights into MXE splicing mechanics and evolution. Finally, MXEs are significantly enriched in pathogenic mutations and their spatio-temporal expression predicts human disease pathology.