(133a) The Genome Sequence of the Chinese Hamster:Ushering In An Era of CHO Genome Engineering

Authors: 
Jacob, N. M., University of Minnesota
Vishwanathan, N., University of Minnesota
Yusufi, F., Bioprocessing Technology Institute A-STAR
Chin, J., Bioprocessing Technology Institute A-STAR
Lee, T. S., Bioprocessing Technology Institute A-STAR
Johnson, K. C., University of Minnesota
Le, H., University of Minnesota
Ramaraj, T., National Center for Genome Resources
Woodward, J., National Center for Genome Resources
Retzel, E. F., National Center for Genome Resources
Crow, J. A., National Center for Genome Resources
Nagarajan, N., Genome Institute of Singapore A-STAR
Ruan, X., Genome Institute of Singapore A-STAR
Ruan, Y., Genome Institute of Singapore A-STAR
Loo, B. L. W., Bioprocessing Technology Institute A-STAR
Lee, D. Y., Bioprocessing Technology institute, A*STAR
Karypis, G., University of Minnesota
Yap, M. G. S., Agency for Science and Technology Research (A*STAR)
Gao, S., Genome Institute of Singapore A-STAR


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.