Dissecting aneuploidy phenotypes by constructing Sc2.0 chromosome VII and SCRaMbLEing synthetic disomic yeast

Yue Shen, Feng Gao, Yun Wang, Yuerong Wang, Ju Zheng, Jianhui Gong, Jintao Zhang, Zhouqing Luo, Daniel Schindler, Yang Deng, Weichao Ding, Tao Lin, Reem Swidah, Hongcui Zhao, Shuangying Jiang, Cheng Zeng, Shihong Chen, Tai Chen, Yong Wang, Yisha LuoLeslie Mitchell, Joel S. Bader, Guojie Zhang, Xia Shen, Jian Wang, Xian Fu, Junbiao Dai, Jef D. Boeke, Huanming Yang, Xun Xu, Yizhi Cai

Research output: Contribution to journalArticlepeer-review


Aneuploidy compromises genomic stability, often leading to embryo inviability, and is frequently associated with tumorigenesis and aging. Different aneuploid chromosome stoichiometries lead to distinct transcriptomic and phenotypic changes, making it helpful to study aneuploidy in tightly controlled genetic backgrounds. By deploying the engineered SCRaMbLE (synthetic chromosome rearrangement and modification by loxP-mediated evolution) system to the newly synthesized megabase Sc2.0 chromosome VII (synVII), we constructed a synthetic disomic yeast and screened hundreds of SCRaMbLEd derivatives with diverse chromosomal rearrangements. Phenotypic characterization and multi-omics analysis revealed that fitness defects associated with aneuploidy could be restored by (1) removing most of the chromosome content or (2) modifying specific regions in the duplicated chromosome. These findings indicate that both chromosome copy number and specific chromosomal regions contribute to the aneuploidy-related phenotypes, and the synthetic chromosome resource opens new paradigms in studying aneuploidy.

Original languageEnglish (US)
Article number100364
JournalCell Genomics
Issue number11
StatePublished - Nov 8 2023


  • SCRaMbLE
  • aneuploidy phenotypes
  • aneuploidy recovery approaches
  • growth rate
  • synVII
  • synthetic disomic yeast
  • synthetic genomics

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Genetics


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