title: Chromosome engineering in zygotes with CRISPR/Cas9.
abstract: Deletions, duplications, and inversions of large genomic regions covering several genes are an important class of disease causing variants in humans. Modeling these structural variants in mice requires multistep processes in ES cells, which has limited their availability. Mutant mice containing small insertions, deletions, and single nucleotide polymorphisms can be reliably generated using CRISPR/Cas9 directly in mouse zygotes. Large structural variants can be generated using CRISPR/Cas9 in ES cells, but it has not been possible to generate these directly in zygotes. We now demonstrate the direct generation of deletions, duplications and inversions of up to one million base pairs by zygote injection.
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, CB10 1SA, Cambridge, United Kingdom.
authors.forename: Katharina
authors.initials: K
authors.lastname: Boroviak
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, CB10 1SA, Cambridge, United Kingdom.
authors.forename: Brendan
authors.initials: B
authors.lastname: Doe
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, CB10 1SA, Cambridge, United Kingdom.
authors.forename: Ruby
authors.initials: R
authors.lastname: Banerjee
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, CB10 1SA, Cambridge, United Kingdom.
authors.forename: Fengtang
authors.initials: F
authors.lastname: Yang
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, CB10 1SA, Cambridge, United Kingdom.
authors.forename: Allan
authors.initials: A
authors.lastname: Bradley
mesh_terms: D000818:Animals; D001483:Base Sequence; D064113:CRISPR-Cas Systems; D058674:Chromosome Duplication; D007446:Chromosome Inversion; D002875:Chromosomes; D004247:DNA; D005240:Feasibility Studies; D005260:Female; D005818:Genetic Engineering / Q000379:methods*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data
chemical_list: D004247:DNA
keywords: CRISPR/Cas9; large structural variants; zygote injection