The Genome Sequence of the Chinese Hamster:Ushering In An Era of CHO Genome Engineering

Monday, October 17, 2011: 3:15 PM
M100 I (Minneapolis Convention Center)
Nitya M. Jacob1, Nandita Vishwanathan1, Faraaz Yusufi2, Ju-Xin Chin2, Terk Shuen Lee2, Kathryn C. Johnson1, Huong Le1, Thiru Ramaraj3, Jimmy Woodward3, Ernest F. Retzel3, John A. Crow3, Song Gao4, Niranjan Nagarajan4, Xiaoan Ruan4, Yijun Ruan4, Bernard L. W. Loo2, Dong-Yup Lee2, George Karypis5, Miranda G. S. Yap2 and Wei-Shou Hu1, (1)Department of Chemical Engineering and Materials Science, University of Minnesota, Minneapolis, MN, (2)Bioprocessing Technology Institute A-STAR, Singapore, (3)National Center for Genome Resources, Santa Fe, NM, (4)Genome Institute of Singapore A-STAR, Singapore, (5)Department of Computer Science and Engineering, University of Minnesota, Minneapolis, MN

CHO cells, the workhorses of the biopharmaceutical industry, are derived from the Chinese hamster, arguably making it the most economically important industrial organism. The synergistic application of high-throughput sequencing technologies, along with the existing CHO EST collection as backbone, enabled the efficient assembly of the Chinese hamster genome. The current assembly (~2.5Gb), constituting over two billion sequence reads, includes more than 25,000 annotated genes across a range of functional classes. This has allowed a global comparative analysis with the mouse, rat and human genomes. Furthermore, the investigation of regulatory features including promoters, CpG Islands and microRNAs has opened up new avenues for manipulating individual gene expression as well as genome level interventions.

In addition, this work aims to study the genetic variation underlying economically important productivity traits in CHO cells, by a comparative genomics approach, with diploid hamster DNA as reference. Further, cell line-specific functional polymorphisms have been identified utilizing RNA-Seq data from several different recombinant lines. The availability of a well-annotated Chinese hamster genome will open up many new opportunities for cell engineering and metabolic intervention for process enhancement.

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