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A simple strategy for heritable chromosomal deletions in zebrafish via the combinatorial action of targeting nucleases

Shimin Lim1, Yin Wang23, Xueyao Yu4, Yian Huang5, Mark S Featherstone1 and Karuna Sampath123*

Author Affiliations

1 School of Biological Sciences, 50 Nanyang Avenue, Nanyang Technological University, Singapore 639798

2 Temasek Life Sciences Laboratory, 1 Research Link, National University of Singapore, Singapore 117604

3 Department of Biological Sciences, National University of Singapore, 14 Science Drive 4, Singapore 117543

4 School of Applied Science, Temasek Polytechnic, 21 Tampines Avenue 1, Singapore 529757

5 NUS High School of Mathematics and Science, 20 Clementi Avenue 1, Singapore 129957

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Genome Biology 2013, 14:R69  doi:10.1186/gb-2013-14-7-r69

Published: 1 July 2013

Abstract

Precise and effective genome-editing tools are essential for functional genomics and gene therapy. Targeting nucleases have been successfully used to edit genomes. However, whole-locus or element-specific deletions abolishing transcript expression have not previously been reported. Here, we show heritable targeting of locus-specific deletions in the zebrafish nodal-related genes squint (sqt) and cyclops (cyc). Our strategy of heritable chromosomal editing can be used for disease modeling, analyzing gene clusters, regulatory regions, and determining the functions of non-coding RNAs in genomes.