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AlleleAnalyzer: a tool for personalized and allele-specific sgRNA design

View ORCID ProfileKathleen C. Keough, Svetlana Lyalina, Michael P. Olvera, View ORCID ProfileSean Whalen, Bruce R. Conklin, View ORCID ProfileKatherine S. Pollard
doi: https://doi.org/10.1101/342923
Kathleen C. Keough
1Pharmaceutical Sciences and Pharmacogenomics Graduate Program at the University of California, San Francisco, California, USA
2Gladstone Institutes, San Francisco, California, USA
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  • ORCID record for Kathleen C. Keough
Svetlana Lyalina
2Gladstone Institutes, San Francisco, California, USA
3Bioinformatics Graduate Program at the University of California, San Francisco, California, USA
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Michael P. Olvera
2Gladstone Institutes, San Francisco, California, USA
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Sean Whalen
2Gladstone Institutes, San Francisco, California, USA
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Bruce R. Conklin
2Gladstone Institutes, San Francisco, California, USA
4Departments of Biostatistics, Medicine, Ophthalmology and Pharmacology, University of California, San Francisco, California, USA
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Katherine S. Pollard
2Gladstone Institutes, San Francisco, California, USA
5Department of Epidemiology & Biostatistics, Institute for Human Genetics, Quantitative Biology Institute, and Institute for Computational Health Sciences, University of California, San Francisco, California, USA
6Chan Zuckerberg Biohub, California, USA
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Abstract

The CRISPR/Cas system is a highly specific genome editing tool capable of distinguishing alleles differing by even a single base pair. However, current tools only design sgRNAs for a reference genome, not taking into account individual variants which may generate, remove, or modify CRISPR/Cas sgRNA sites. This may cause mismatches between designed sgRNAs and the individual genome they are intended to target, leading to decreased experimental performance. Here we describe AlleleAnalyzer, a tool for designing personalized and allele-specific sgRNAs for genome editing. We leverage >2,500 human genomes to identify optimized pairs of sgRNAs that can be used for human therapeutic editing in large populations in the future.

  • List of Abbreviations

    sgRNA
    single-guide RNA
    PAM site
    protospacer adjacent motif site
    1KGP
    1000 Genomes Project
    kb
    kilobases (1000 genomic basepairs)
    iPSC
    induced pluripotent stem cell
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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 September 11, 2018.
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    AlleleAnalyzer: a tool for personalized and allele-specific sgRNA design
    Kathleen C. Keough, Svetlana Lyalina, Michael P. Olvera, Sean Whalen, Bruce R. Conklin, Katherine S. Pollard
    bioRxiv 342923; doi: https://doi.org/10.1101/342923
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    AlleleAnalyzer: a tool for personalized and allele-specific sgRNA design
    Kathleen C. Keough, Svetlana Lyalina, Michael P. Olvera, Sean Whalen, Bruce R. Conklin, Katherine S. Pollard
    bioRxiv 342923; doi: https://doi.org/10.1101/342923

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