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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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© 2014 Elsevier B.V.
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http://www.ncbi.nlm.nih.gov/pubmed/25660031 (beliebiger Volltext)
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 Urheber:
Kraft, K.1, Autor           
Geuer, S.2, Autor
Will, A. J.2, Autor
Chan, W. L., Autor
Paliou, C.2, Autor
Borschiwer, M.2, Autor
Harabula, I.2, Autor
Wittler, L.3, Autor           
Franke, M.1, Autor           
Ibrahim, D.1, Autor           
Kragesteen, B. K.2, Autor
Spielmann, M.1, Autor           
Mundlos, S.1, Autor           
Lupianez, D. G.2, Autor
Andrey, G.2, Autor
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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 Zusammenfassung: 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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Sprache(n): eng - English
 Datum: 2015-02-042015-02-10
 Publikationsstatus: Erschienen
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 Inhaltsverzeichnis: -
 Art der Begutachtung: Expertenbegutachtung
 Identifikatoren: DOI: 10.1016/j.celrep.2015.01.016
ISSN: 2211-1247 (Electronic)
 Art des Abschluß: -

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Titel: Cell Reports
Genre der Quelle: Zeitschrift
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Ort, Verlag, Ausgabe: Elsevier
Seiten: - Band / Heft: 10 (5) Artikelnummer: - Start- / Endseite: 833 - 839 Identifikator: Anderer: 2211-1247
CoNE: https://pure.mpg.de/cone/journals/resource/2211-1247