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CRISPR-directed mitotic recombination enables genetic mapping without crosses

Meru J. Sadhu, Joshua S. Bloom, Laura Day, Leonid Kruglyak
doi: https://doi.org/10.1101/040428
Meru J. Sadhu
Department of Human Genetics, Department of Biological Chemistry, and Howard Hughes Medical Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA
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  • For correspondence: msadhu@mednet.ucla.edu jbloom@mednet.ucla.edu lkruglyak@mednet.ucla.edu
Joshua S. Bloom
Department of Human Genetics, Department of Biological Chemistry, and Howard Hughes Medical Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA
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  • For correspondence: msadhu@mednet.ucla.edu jbloom@mednet.ucla.edu lkruglyak@mednet.ucla.edu
Laura Day
Department of Human Genetics, Department of Biological Chemistry, and Howard Hughes Medical Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA
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Leonid Kruglyak
Department of Human Genetics, Department of Biological Chemistry, and Howard Hughes Medical Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA
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  • For correspondence: msadhu@mednet.ucla.edu jbloom@mednet.ucla.edu lkruglyak@mednet.ucla.edu
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Abstract

Linkage and association studies have mapped thousands of genomic regions that contribute to phenotypic variation, but narrowing these regions to the underlying causal genes and variants has proven much more challenging. Resolution of genetic mapping is limited by the recombination rate. We developed a method that uses CRISPR to build mapping panels with targeted recombination events. We tested the method by generating a panel with recombination events spaced along a yeast chromosome arm, mapping trait variation, and then targeting a high density of recombination events to the region of interest. Using this approach, we fine-mapped manganese sensitivity to a single polymorphism in the transporter Pmr1. Targeting recombination events to regions of interest allows us to rapidly and systematically identify causal variants underlying trait differences.

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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-NC-ND 4.0 International license.
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Posted February 19, 2016.
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CRISPR-directed mitotic recombination enables genetic mapping without crosses
Meru J. Sadhu, Joshua S. Bloom, Laura Day, Leonid Kruglyak
bioRxiv 040428; doi: https://doi.org/10.1101/040428
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CRISPR-directed mitotic recombination enables genetic mapping without crosses
Meru J. Sadhu, Joshua S. Bloom, Laura Day, Leonid Kruglyak
bioRxiv 040428; doi: https://doi.org/10.1101/040428

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