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Bug mapping and fitness testing of chemically synthesized chromosome X

Wu, Yi and Li, Bing-Zhi and Zhao, Meng and Mitchell, Leslie A and Xie, Ze-Xiong and Lin, Qiu-Hui and Wang, Xia and Xiao, Wen-Hai and Wang, Ying and Zhou, Xiao and Liu, Hong and Li, Xia and Ding, Ming-Zhu and Liu, Duo and Zhang, Lu and Liu, Bao-Li and Wu, Xiao-Le and Li, Fei-Fei and Dong, Xiu-Tao and Jia, Bin and Zhang, Wen-Zheng and Jiang, Guo-Zhen and Liu, Yue and Bai, Xue and Song, Tian-Qing and Chen, Yan and Zhou, Si-Jie and Zhu, Rui-Ying and Gao, Feng and Kuang, Zheng and Wang, Xuya and Shen, Michael and Yang, Kun and Stracquadanio, Giovanni and Richardson, Sarah M and Lin, Yicong and Wang, Lihui and Walker, Roy and Luo, Yisha and Ma, Ping-Sheng and Yang, Huanming and Cai, Yizhi and Dai, Junbiao and Bader, Joel S and Boeke, Jef D and Yuan, Ying-Jin (2017) 'Bug mapping and fitness testing of chemically synthesized chromosome X.' Science, 355 (6329). ISSN 0036-8075

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Abstract

Debugging a genome sequence is imperative for successfully building a synthetic genome. As part of the effort to build a designer eukaryotic genome, yeast synthetic chromosome X (synX), designed as 707,459 base pairs, was synthesized chemically. SynX exhibited good fitness under a wide variety of conditions. A highly efficient mapping strategy called pooled PCRTag mapping (PoPM), which can be generalized to any watermarked synthetic chromosome, was developed to identify genetic alterations that affect cell fitness (“bugs”). A series of bugs were corrected that included a large region bearing complex amplifications, a growth defect mapping to a recoded sequence in FIP1, and a loxPsym site affecting promoter function of ATP2. PoPM is a powerful tool for synthetic yeast genome debugging and an efficient strategy for phenotype-genotype mapping.

Item Type: Article
Subjects: Q Science > Q Science (General)
Q Science > QA Mathematics > QA75 Electronic computers. Computer science
Q Science > QA Mathematics > QA76 Computer software
Q Science > QD Chemistry
Divisions: Faculty of Science and Health > Computer Science and Electronic Engineering, School of
Depositing User: Giovanni Stracquadanio
Date Deposited: 15 May 2017 09:36
Last Modified: 05 Jul 2018 10:15
URI: http://repository.essex.ac.uk/id/eprint/19591

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