CRISPR-directed mitotic recombination enables genetic mapping without crosses

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...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2016-05, Vol.352 (6289), p.1113-1116
Main Authors: Sadhu, Meru J., Bloom, Joshua S., Day, Laura, Kruglyak, Leonid
Format: Article
Language:English
Subjects:
Amino Acid Substitution
Bacterial Proteins - metabolism
Calcium-Transporting ATPases - genetics
Chromosome Mapping - methods
Chromosomes, Fungal
Clustered Regularly Interspaced Short Palindromic Repeats
Construction
CRISPR-Associated Protein 9
Crosses, Genetic
DNA Breaks, Double-Stranded
Drug Resistance, Fungal - genetics
Endonucleases - metabolism
Genes
Genetic Linkage
Genetics
Leucine - genetics
Loci
Loss of Heterozygosity
Manganese
Manganese - pharmacology
Mapping
Mitosis - genetics
Molecular Chaperones
Mutation
Panels
Polymorphism, Single Nucleotide
Recombination, Genetic
Saccharomyces cerevisiae - drug effects
Saccharomyces cerevisiae - genetics
Saccharomyces cerevisiae Proteins - genetics
Studies
Yeast
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Summary: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 (clustered, regularly interspaced, short palindromic repeats) 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.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.aaf5124