Genomic landscapes of Chinese hamster ovary cell lines as revealed by the Cricetulus griseus draft genome.

Nathan E Lewis; Xin Liu; Yuxiang Li; Harish Nagarajan; George Yerganian; Edward O'Brien; Aarash Bordbar; Anne M Roth; Jeffrey Rosenbloom; Chao Bian; Min Xie; Wenbin Chen; Ning Li; Deniz Baycin-Hizal; Haythem Latif; Jochen Förster; Michael Betenbaugh; Iman Famili; Xun Xu; Jun Wang; Bernhard O Palsson

doi:10.1038/nbt.2624

Genomic landscapes of Chinese hamster ovary cell lines as revealed by the Cricetulus griseus draft genome.

Nathan E Lewis, Xin Liu, Yuxiang Li, Harish Nagarajan, George Yerganian, Edward O'Brien, Aarash Bordbar, Anne M Roth, Jeffrey Rosenbloom, Chao Bian, Min Xie, Wenbin Chen, Ning Li, Deniz Baycin-Hizal, Haythem Latif, Jochen Förster, Michael Betenbaugh, Iman Famili, Xun Xu, Jun WangBernhard O Palsson

Novo Nordisk Foundation Center for Biosustainability

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Abstract

Chinese hamster ovary (CHO) cells, first isolated in 1957, are the preferred production host for many therapeutic proteins. Although genetic heterogeneity among CHO cell lines has been well documented, a systematic, nucleotide-resolution characterization of their genotypic differences has been stymied by the lack of a unifying genomic resource for CHO cells. Here we report a 2.4-Gb draft genome sequence of a female Chinese hamster, Cricetulus griseus, harboring 24,044 genes. We also resequenced and analyzed the genomes of six CHO cell lines from the CHO-K1, DG44 and CHO-S lineages. This analysis identified hamster genes missing in different CHO cell lines, and detected >3.7 million single-nucleotide polymorphisms (SNPs), 551,240 indels and 7,063 copy number variations. Many mutations are located in genes with functions relevant to bioprocessing, such as apoptosis. The details of this genetic diversity highlight the value of the hamster genome as the reference upon which CHO cells can be studied and engineered for protein production.

Original language	English
Journal	Nature Biotechnology
Volume	31
Pages (from-to)	759-765
ISSN	1087-0156
DOIs	https://doi.org/10.1038/nbt.2624
Publication status	Published - 2013

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Lewis, N. E., Liu, X., Li, Y., Nagarajan, H., Yerganian, G., O'Brien, E., Bordbar, A., Roth, A. M., Rosenbloom, J., Bian, C., Xie, M., Chen, W., Li, N., Baycin-Hizal, D., Latif, H., Förster, J., Betenbaugh, M., Famili, I., Xu, X., ... Palsson, B. O. (2013). Genomic landscapes of Chinese hamster ovary cell lines as revealed by the Cricetulus griseus draft genome. Nature Biotechnology, 31, 759-765. https://doi.org/10.1038/nbt.2624

@article{5e57cd4bb5674bee9ea3264e08ac9905,

title = "Genomic landscapes of Chinese hamster ovary cell lines as revealed by the Cricetulus griseus draft genome.",

abstract = "Chinese hamster ovary (CHO) cells, first isolated in 1957, are the preferred production host for many therapeutic proteins. Although genetic heterogeneity among CHO cell lines has been well documented, a systematic, nucleotide-resolution characterization of their genotypic differences has been stymied by the lack of a unifying genomic resource for CHO cells. Here we report a 2.4-Gb draft genome sequence of a female Chinese hamster, Cricetulus griseus, harboring 24,044 genes. We also resequenced and analyzed the genomes of six CHO cell lines from the CHO-K1, DG44 and CHO-S lineages. This analysis identified hamster genes missing in different CHO cell lines, and detected >3.7 million single-nucleotide polymorphisms (SNPs), 551,240 indels and 7,063 copy number variations. Many mutations are located in genes with functions relevant to bioprocessing, such as apoptosis. The details of this genetic diversity highlight the value of the hamster genome as the reference upon which CHO cells can be studied and engineered for protein production.",

author = "Lewis, {Nathan E} and Xin Liu and Yuxiang Li and Harish Nagarajan and George Yerganian and Edward O'Brien and Aarash Bordbar and Roth, {Anne M} and Jeffrey Rosenbloom and Chao Bian and Min Xie and Wenbin Chen and Ning Li and Deniz Baycin-Hizal and Haythem Latif and Jochen F{\"o}rster and Michael Betenbaugh and Iman Famili and Xun Xu and Jun Wang and Palsson, {Bernhard O}",

year = "2013",

doi = "10.1038/nbt.2624",

language = "English",

volume = "31",

pages = "759--765",

journal = "Nature Biotechnology",

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Lewis, NE, Liu, X, Li, Y, Nagarajan, H, Yerganian, G, O'Brien, E, Bordbar, A, Roth, AM, Rosenbloom, J, Bian, C, Xie, M, Chen, W, Li, N, Baycin-Hizal, D, Latif, H, Förster, J, Betenbaugh, M, Famili, I, Xu, X, Wang, J & Palsson, BO 2013, 'Genomic landscapes of Chinese hamster ovary cell lines as revealed by the Cricetulus griseus draft genome.', Nature Biotechnology, vol. 31, pp. 759-765. https://doi.org/10.1038/nbt.2624

TY - JOUR

T1 - Genomic landscapes of Chinese hamster ovary cell lines as revealed by the Cricetulus griseus draft genome.

AU - Lewis, Nathan E

AU - Liu, Xin

AU - Li, Yuxiang

AU - Nagarajan, Harish

AU - Yerganian, George

AU - O'Brien, Edward

AU - Bordbar, Aarash

AU - Roth, Anne M

AU - Rosenbloom, Jeffrey

AU - Bian, Chao

AU - Xie, Min

AU - Chen, Wenbin

AU - Li, Ning

AU - Baycin-Hizal, Deniz

AU - Latif, Haythem

AU - Förster, Jochen

AU - Betenbaugh, Michael

AU - Famili, Iman

AU - Xu, Xun

AU - Wang, Jun

AU - Palsson, Bernhard O

PY - 2013

Y1 - 2013

N2 - Chinese hamster ovary (CHO) cells, first isolated in 1957, are the preferred production host for many therapeutic proteins. Although genetic heterogeneity among CHO cell lines has been well documented, a systematic, nucleotide-resolution characterization of their genotypic differences has been stymied by the lack of a unifying genomic resource for CHO cells. Here we report a 2.4-Gb draft genome sequence of a female Chinese hamster, Cricetulus griseus, harboring 24,044 genes. We also resequenced and analyzed the genomes of six CHO cell lines from the CHO-K1, DG44 and CHO-S lineages. This analysis identified hamster genes missing in different CHO cell lines, and detected >3.7 million single-nucleotide polymorphisms (SNPs), 551,240 indels and 7,063 copy number variations. Many mutations are located in genes with functions relevant to bioprocessing, such as apoptosis. The details of this genetic diversity highlight the value of the hamster genome as the reference upon which CHO cells can be studied and engineered for protein production.

AB - Chinese hamster ovary (CHO) cells, first isolated in 1957, are the preferred production host for many therapeutic proteins. Although genetic heterogeneity among CHO cell lines has been well documented, a systematic, nucleotide-resolution characterization of their genotypic differences has been stymied by the lack of a unifying genomic resource for CHO cells. Here we report a 2.4-Gb draft genome sequence of a female Chinese hamster, Cricetulus griseus, harboring 24,044 genes. We also resequenced and analyzed the genomes of six CHO cell lines from the CHO-K1, DG44 and CHO-S lineages. This analysis identified hamster genes missing in different CHO cell lines, and detected >3.7 million single-nucleotide polymorphisms (SNPs), 551,240 indels and 7,063 copy number variations. Many mutations are located in genes with functions relevant to bioprocessing, such as apoptosis. The details of this genetic diversity highlight the value of the hamster genome as the reference upon which CHO cells can be studied and engineered for protein production.

U2 - 10.1038/nbt.2624

DO - 10.1038/nbt.2624

M3 - Journal article

SN - 1087-0156

VL - 31

SP - 759

EP - 765

JO - Nature Biotechnology

JF - Nature Biotechnology

ER -

Genomic landscapes of Chinese hamster ovary cell lines as revealed by the Cricetulus griseus draft genome.

Abstract

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