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The landscape of human mutually exclusive splicing.

MPG-Autoren
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Hatje,  K.
Research Group of Systems Biology of Motor Proteins, MPI for biophysical chemistry, Max Planck Society;

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Simm,  D.
Research Group of Systems Biology of Motor Proteins, MPI for biophysical chemistry, Max Planck Society;

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Hammesfahr,  B.
Research Group of Systems Biology of Motor Proteins, MPI for biophysical chemistry, Max Planck Society;

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Kollmar,  M.
Research Group of Systems Biology of Motor Proteins, MPI for biophysical chemistry, Max Planck Society;

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Zitation

Hatje, K., Rahman, R. U., Vidal, R. O., Simm, D., Hammesfahr, B., Bansal, V., et al. (2017). The landscape of human mutually exclusive splicing. Molecular Systems Biology, 13(12): 959. doi:10.15252/msb.20177728.


Zitierlink: https://hdl.handle.net/11858/00-001M-0000-002E-8F7C-0
Zusammenfassung
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.