PUBLICATION

Swift Large-scale Examination of Directed Genome Editing

Authors
Hammouda, O.T., Böttger, F., Wittbrodt, J., Thumberger, T.
ID
ZDB-PUB-190306-15
Date
2019
Source
PLoS One   14: e0213317 (Journal)
Registered Authors
Wittbrodt, Jochen
Keywords
none
MeSH Terms
  • Animals
  • Animals, Genetically Modified/genetics*
  • CRISPR-Cas Systems*
  • Embryo, Nonmammalian/cytology
  • Embryo, Nonmammalian/metabolism
  • Gene Editing/methods*
  • Gene Knockout Techniques/methods*
  • Genome
  • Oryzias/genetics*
  • Zebrafish/genetics*
PubMed
30835740 Full text @ PLoS One
Abstract
In the era of CRISPR gene editing and genetic screening, there is an increasing demand for quick and reliable nucleic acid extraction pipelines for rapid genotyping of large and diverse sample sets. Despite continuous improvements of current workflows, the handling-time and material costs per sample remain major limiting factors. Here we present a robust method for low-cost DIY-pipet tips addressing these needs; i.e. using a cellulose filter disc inserted into a regular pipet tip. These filter-in-tips allow for a rapid, stand-alone four-step genotyping workflow by simply binding the DNA contained in the primary lysate to the cellulose filter, washing it in water and eluting it directly into the buffer for the downstream application (e.g. PCR). This drastically cuts down processing time to maximum 30 seconds per sample, with the potential for parallelizing and automation. We show the ease and sensitivity of our procedure by genotyping genetically modified medaka (Oryzias latipes) and zebrafish (Danio rerio) embryos (targeted by CRISPR/Cas9 knock-out and knock-in) in a 96-well plate format. The robust isolation and detection of multiple alleles of various abundancies in a mosaic genetic background allows phenotype-genotype correlation already in the injected generation, demonstrating the reliability and sensitivity of the protocol. Our method is applicable across kingdoms to samples ranging from cells to tissues i. e. plant seedlings, adult flies, mouse cell culture and tissue as well as adult fish fin-clips.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping