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The impact of sex on alternative splicing

Guy Karlebach, Diogo F.T. Veiga, Anne Deslattes Mays, Anil K. Kesarwani, Daniel Danis, Georgios Kararigas, Xingmin Aaron Zhang, Joshy George, Guru Ananda, Robin Steinhaus, Peter Hansen, Dominik Seelow, Chris Bizon, Rebecca Boyles, Chris Ball, Julie A McMurry, Melissa A Haendel, Jeremy Yang, Tudor Oprea, Mitali Mukerji, Olga Anczukow, Jacques Banchereau, Peter N Robinson
doi: https://doi.org/10.1101/490904
Guy Karlebach
The Jackson Laboratory for Genomic Medicine, Farmington CT 06032, USA
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Diogo F.T. Veiga
The Jackson Laboratory for Genomic Medicine, Farmington CT 06032, USA
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Anne Deslattes Mays
The Jackson Laboratory for Genomic Medicine, Farmington CT 06032, USA
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Anil K. Kesarwani
The Jackson Laboratory for Genomic Medicine, Farmington CT 06032, USA
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Daniel Danis
The Jackson Laboratory for Genomic Medicine, Farmington CT 06032, USA
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Georgios Kararigas
Charité-Universita□tsmedizin Berlin, Charitéplatz 1, 10115 Berlin, GermanyDZHK (German Centre for Cardiovascular Research), partner site Berlin, Germany
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Xingmin Aaron Zhang
The Jackson Laboratory for Genomic Medicine, Farmington CT 06032, USA
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Joshy George
The Jackson Laboratory for Genomic Medicine, Farmington CT 06032, USA
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Guru Ananda
The Jackson Laboratory for Genomic Medicine, Farmington CT 06032, USA
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Robin Steinhaus
Charité-Universita□tsmedizin Berlin, Charitéplatz 1, 10115 Berlin, Germany
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Peter Hansen
Charité-Universita□tsmedizin Berlin, Charitéplatz 1, 10115 Berlin, Germany
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Dominik Seelow
Charité-Universita□tsmedizin Berlin, Charitéplatz 1, 10115 Berlin, Germany
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Chris Bizon
Renaissance Computing Institute (RENCI), 100 Europa Drive, Suite 540, Chapel Hill, NC 27517, United States
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Rebecca Boyles
RTI International, Durham, NC 27709, USA
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Chris Ball
RTI International, Durham, NC 27709, USA
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Julie A McMurry
Linus Pauling institute, Oregon State University, Corvallis OR, USA
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Melissa A Haendel
Linus Pauling institute, Oregon State University, Corvallis OR, USA
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Jeremy Yang
Translational Informatics Division, Department of Internal Medicine, The University of New Mexico Health Science Center, Albuquerque, NM 87131, USA
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Tudor Oprea
Translational Informatics Division, Department of Internal Medicine, The University of New Mexico Health Science Center, Albuquerque, NM 87131, USA
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Mitali Mukerji
Genomics and Molecular Medicine, CSIR-Institute of Genomics and Integrative Biology, Mathura Road (CSIR-IGIB), Mathura Road, New Delhi 110 025, India. E-mail: mitali@igib.res.in,
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  • For correspondence: mitali@igib.res.in
Olga Anczukow
The Jackson Laboratory for Genomic Medicine, Farmington CT 06032, USA
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Jacques Banchereau
The Jackson Laboratory for Genomic Medicine, Farmington CT 06032, USA
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Peter N Robinson
The Jackson Laboratory for Genomic Medicine, Farmington CT 06032, USAInstitute for Systems Genomics, University of Connecticut, Farmington, CT, USA
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  • For correspondence: peter.robinson@jax.org
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Abstract

Over 95% of human genes undergo alternative splicing (AS) in a developmental, tissue-specific, or signal transduction-dependent manner. A number of factors including binding of cis-acting sequences by RNA-binding proteins (RBPs) are known to affect AS, but the combinatorial mechanisms leading to the distribution of spliced isoforms remain largely unstudied. Here, in 9011 samples from 532 individuals across 53 tissues from the Genotype-Tissue Expression (GTEx) resource, we identified 4,135 genes with sex-biased expression and 5,925 sex-biased AS events. We find that factors including escape from X-chromosomal inactivation, presence of Alu elements, and oestrogen receptor binding sites affect sex-biased AS. We utilize hierarchical Bayesian modelling to characterize the interactions of exon skipping, gene expression, and RBPs, and demonstrate two categories of sex-biased AS that differ with respect to splice site scores, gene expression, RBP levels, and skipping/inclusion ratio.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted December 10, 2018.
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The impact of sex on alternative splicing
Guy Karlebach, Diogo F.T. Veiga, Anne Deslattes Mays, Anil K. Kesarwani, Daniel Danis, Georgios Kararigas, Xingmin Aaron Zhang, Joshy George, Guru Ananda, Robin Steinhaus, Peter Hansen, Dominik Seelow, Chris Bizon, Rebecca Boyles, Chris Ball, Julie A McMurry, Melissa A Haendel, Jeremy Yang, Tudor Oprea, Mitali Mukerji, Olga Anczukow, Jacques Banchereau, Peter N Robinson
bioRxiv 490904; doi: https://doi.org/10.1101/490904
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The impact of sex on alternative splicing
Guy Karlebach, Diogo F.T. Veiga, Anne Deslattes Mays, Anil K. Kesarwani, Daniel Danis, Georgios Kararigas, Xingmin Aaron Zhang, Joshy George, Guru Ananda, Robin Steinhaus, Peter Hansen, Dominik Seelow, Chris Bizon, Rebecca Boyles, Chris Ball, Julie A McMurry, Melissa A Haendel, Jeremy Yang, Tudor Oprea, Mitali Mukerji, Olga Anczukow, Jacques Banchereau, Peter N Robinson
bioRxiv 490904; doi: https://doi.org/10.1101/490904

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