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Engineering microdeletions and microduplications by targeting segmental duplications with CRISPR

Title
Engineering microdeletions and microduplications by targeting segmental duplications with CRISPR
Authors
Tai D.J.C.Ragavendran A.Manavalan P.Stortchevoi A.Seabra C.M.Erdin S.Collins R.L.Blumenthal I.Chen X.Shen Y.Sahin M.Zhang C.Lee C.Gusella J.F.Talkowski M.E.
Ewha Authors
Charles Lee
SCOPUS Author ID
Charles Leescopus
Issue Date
2016
Journal Title
Nature Neuroscience
ISSN
1097-6256JCR Link
Citation
vol. 19, no. 3, pp. 517 - 522
Publisher
Nature Publishing Group
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Recurrent, reciprocal genomic disorders resulting from non-allelic homologous recombination (NAHR) between near-identical segmental duplications (SDs) are a major cause of human disease, often producing phenotypically distinct syndromes. The genomic architecture of flanking SDs presents a challenge for modeling these syndromes; however, the capability to efficiently generate reciprocal copy number variants (CNVs) that mimic NAHR would represent a valuable modeling tool. We describe here a CRISPR/Cas9 genome engineering method, single-guide CRISPR/Cas targeting of repetitive elements (SCORE), to model reciprocal genomic disorders and demonstrate its capabilities by generating reciprocal CNVs of 16p11.2 and 15q13.3, including alteration of one copy-equivalent of the SDs that mediate NAHR in vivo. The method is reproducible, and RNA sequencing reliably clusters transcriptional signatures from human subjects with in vivo CNVs and their corresponding in vitro models. This new approach will provide broad applicability for the study of genomic disorders and, with further development, may also permit efficient correction of these defects. © 2016 Nature America, Inc. All rights reserved.
DOI
10.1038/nn.4235
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일반대학원 > 생명과학과 > Journal papers
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