Chinese Hamster Ovary (CHO) cells are widely used for large scale production of recombinant biopharmaceuticals. During subsequent cell culture, the chromosome number and structure of CHO cells undergo rapid change. Over the course of cultivation, selection, and adaptation, chromosomal aberrations such as mutations, deletions, duplications, and other structural variants can accumulate. Some genomic regions may be more prone to such instability than others. Creative Bioarray can analyze the genome stability of CHO cell lines at macroscopic and microscopic levels. At the macroscopic level, we examined chromosomal and karyotypic variation, observing the progenies of single cell clones quickly developed widely distributed variants with different numbers and types of chromosomes. However, at the population level the karyotype and chromosomal number distribution remained in a similar range. Stability at the microscope level is analyzed using a gene-coding region focused comparative genomic hybridization (CGH) microarray, allowing us to determine genomic variations in gene copy number.
With CGH data for many parent-daughter relationships, including subclones and relationships between host and producing cell lines, Creative Bioarray can select sites ideal for targeted integration of transgenes as well as screen out potentially unstable cell lines developed using random integration.
Array Comparative Genomic Hybridization (aCGH) is a high-resolution karyotype analysis solution for the detection of unbalanced structural and numerical chromosomal alterations with high-throughput capabilities. Addition of SNPs can also detect polyploidy, loss of heterozygosity, and uniparental disomy. This method has significantly high resolution, which overcomes the limitation of traditional karyotyping (G-banded) as even high-resolution karyotypes are unreliable for detection of many known microdeletion syndromes which range from 3-5 Mb in size.
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