| Citation |
NARVA, Elisa, Reija AUTIO, Nelly RAHKONEN, Lingjia KONG, Neil
HARRISON, Danny KITSBERG, Lodovica BORGHESE, Joseph
ITSKOVITZ-ELDOR, Omid RASOOL, Petr DVOŘÁK, Outi HOVATTA, Timo
OTONSKI, Timo TUURI, Wei CUI, Oliver BRUSTLE, Duncan BAKER,
Edna MALTBY, Harry D. MOORE, Nissim BEVENISTY, Peter W.
ANDREWS, Olli YLI-HARJA and Riita LAHESMAA. High-resolution DNA
analysis of human embryonic stem cell lines reveals
culture-induced copy number changes and loss of heterozygosity.
Nature Biotechnology. 2010, vol. 28, No 4, 7 pp. ISSN
1087-0156. |
| Description |
Prolonged culture of human embryonic stem cells (hESCs) can lead to adaptation and the acquisition of chromosomal abnormalities, underscoring the need for rigorous genetic analysis of these cells. Here we report the highest-resolution study of hESCs to date using an Affymetrix SNP 6.0 array containing 906,600 probes for single nucleotide polymorphisms (SNPs) and 946,000 probes for copy number variations (CNVs). Analysis of 17 different hESC lines maintained in different laboratories identified 843 CNVs of 50 kb-3 Mb in size. We identified, on average, 24% of the loss of heterozygosity (LOH) sites and 66% of the CNVs changed in culture between early and late passages of the same lines. Thirty percent of the genes detected within CNV sites had altered expression compared to samples with normal copy number states, of which >44% were functionally linked to cancer. Furthermore, LOH of the q arm of chromosome 16, which has not been observed previously in hESCs, was detected.
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