CHOmics, Inc., San Diego, California, USA.
Nat Biotechnol. 2013 Aug;31(8):759-65. doi: 10.1038/nbt.2624. Epub 2013 Jul 21.
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.
中国仓鼠卵巢（CHO）细胞于 1957 年首次分离，是许多治疗性蛋白的首选生产宿主。尽管 CHO 细胞系之间存在遗传异质性已得到充分证实，但由于缺乏 CHO 细胞的统一基因组资源，对其基因型差异进行系统的核苷酸分辨率特征描述一直受到阻碍。在这里，我们报告了一只雌性中国仓鼠（Cricetulus griseus）的 2.4-Gb 草图基因组序列，其中包含 24044 个基因。我们还对来自 CHO-K1、DG44 和 CHO-S 谱系的 6 个 CHO 细胞系的基因组进行了重测序和分析。这项分析确定了不同 CHO 细胞系中缺失的仓鼠基因，并检测到超过 370 万个单核苷酸多态性（SNP）、551240 个插入缺失和 7063 个拷贝数变异。许多突变位于与生物加工相关的基因中，如凋亡。这种遗传多样性的细节突出了仓鼠基因组作为 CHO 细胞研究和工程化用于蛋白质生产的参考基因组的价值。
