High-resolution DNA analysis of human embryonic stem cell lines reveals culture-induced copy number changes and loss of heterozygosity

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Authors

NARVA Elisa AUTIO Reija RAHKONEN Nelly KONG Lingjia HARRISON Neil KITSBERG Danny BORGHESE Lodovica ITSKOVITZ-ELDOR Joseph RASOOL Omid DVOŘÁK Petr HOVATTA Outi OTONSKI Timo TUURI Timo CUI Wei BRUSTLE Oliver BAKER Duncan MALTBY Edna MOORE Harry D. BEVENISTY Nissim ANDREWS Peter W. YLI-HARJA Olli LAHESMAA Riita

Year of publication 2010
Type Article in Periodical
Magazine / Source Nature Biotechnology
MU Faculty or unit

Faculty of Medicine

Citation
Field Genetics and molecular biology
Keywords COMPARATIVE GENOMIC HYBRIDIZATION; ES CELLS; INSTABILITY; EXPRESSION; CANCER; CHROMOSOME-16; CARCINOMA; GENES
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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