Email updates

Keep up to date with the latest news and content from BMC Genomics and BioMed Central.

Open Access Highly Accessed Research article

Multiplex genomic structure variation mediated by TALEN and ssODN

Sanyuan Ma1, Xiaogang Wang1, Yuanyuan Liu1, Jie Gao1, Shengling Zhang1, Run Shi1, Jiasong Chang1, Ping Zhao1 and Qingyou Xia12*

Author Affiliations

1 State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, China

2 Present Address: State Key Laboratory of Silkworm Genome Biology, Southwest University, Beibei, Chongqing 400716, China

For all author emails, please log on.

BMC Genomics 2014, 15:41  doi:10.1186/1471-2164-15-41

Published: 18 January 2014

Abstract

Background

Genomic structure variation (GSV) is widely distributed in various organisms and is an important contributor to human diversity and disease susceptibility. Efficient approaches to induce targeted genomic structure variation are crucial for both analytic and therapeutic studies of GSV. Here, we presented an efficient strategy to induce targeted GSV including chromosomal deletions, duplications and inversions in a precise manner.

Results

Utilizing Transcription Activator-Like Effector Nucleases (TALEN) designed to target two distinct sites, we demonstrated targeted deletions, duplications and inversions of an 8.9 Mb chromosomal segment, which is about one third of the entire chromosome. We developed a novel method by combining TALEN-induced GSV and single stranded oligodeoxynucleotide (ssODN) mediated gene modifications to reduce unwanted mutations occurring during the targeted GSV using TALEN or Zinc finger nuclease (ZFN). Furthermore, we showed that co-introduction of TALEN and ssODN generated unwanted complex structure variation other than the expected chromosomal deletion.

Conclusions

We demonstrated the ability of TALEN to induce targeted GSV and provided an efficient strategy to perform GSV precisely. Furthermore, it is the first time to show that co-introduction of TALEN and ssODN generated unwanted complex structure variation. It is plausible to believe that the strategies developed in this study can be applied to other organisms, and will help understand the biological roles of GSV and therapeutic applications of TALEN and ssODN.

Keywords:
TAL Effectors; Genomic structure variation; Chromosomal deletion; Chromosomal duplication; Chromosomal inversion; ssODN