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  Deletions, Inversions, Duplications: Engineering of Structural Variants using CRISPR/Cas in Mice

Kraft, K., Geuer, S., Will, A. J., Chan, W. L., Paliou, C., Borschiwer, M., et al. (2015). Deletions, Inversions, Duplications: Engineering of Structural Variants using CRISPR/Cas in Mice. Cell Reports, 10(5), 833-839. doi:10.1016/j.celrep.2015.01.016.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0025-78F1-2 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0025-78F2-F
Genre: Journal Article

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© 2014 Elsevier B.V.
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 Creators:
Kraft, K.1, Author              
Geuer, S.2, Author
Will, A. J.2, Author
Chan, W. L., Author
Paliou, C.2, Author
Borschiwer, M.2, Author
Harabula, I.2, Author
Wittler, L.3, Author              
Franke, M.1, Author              
Ibrahim, D.1, Author              
Kragesteen, B. K.2, Author
Spielmann, M.1, Author              
Mundlos, S.1, Author              
Lupianez, D. G.2, Author
Andrey, G.2, Author
Affiliations:
1Research Group Development & Disease (Head: Stefan Mundlos), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433557              
2Max Planck Society, ou_persistent13              
3Dept. of Developmental Genetics (Head: Bernhard G. Herrmann), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433548              

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 Abstract: Structural variations (SVs) contribute to the variability of our genome and are often associated with disease. Their study in model systems was hampered until now by labor-intensive genetic targeting procedures and multiple mouse crossing steps. Here we present the use of CRISPR/Cas for the fast (10 weeks) and efficient generation of SVs in mice. We specifically produced deletions, inversions, and also duplications at six different genomic loci ranging from 1.1 kb to 1.6 Mb with efficiencies up to 42%. After PCR-based selection, clones were successfully used to create mice via aggregation. To test the practicability of the method, we reproduced a human 500 kb disease-associated deletion and were able to recapitulate the human phenotype in mice. Furthermore, we evaluated the regulatory potential of a large genomic interval by deleting a 1.5 Mb fragment. The method presented permits rapid in vivo modeling of genomic rearrangements.

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Language(s): eng - English
 Dates: 2015-02-042015-02-10
 Publication Status: Published in print
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 Rev. Method: Peer
 Identifiers: DOI: 10.1016/j.celrep.2015.01.016
ISSN: 2211-1247 (Electronic)
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Title: Cell Reports
Source Genre: Journal
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Publ. Info: Elsevier
Pages: - Volume / Issue: 10 (5) Sequence Number: - Start / End Page: 833 - 839 Identifier: Other: 2211-1247
CoNE: /journals/resource/2211-1247