Journal
NATURE BIOTECHNOLOGY
Volume 28, Issue 4, Pages 371-U103Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nbt.1615
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Funding
- European Union
- Juvenile Diabetes Research Foundation
- Academy of Finland
- Improving Outcomes Guidance Trust
- Ministry of Education, Youth, and Sport of the Czech Republic
- Ida Montin Foundation
- Academy of Finland [129657, 134117]
- Medical Research Council, UK
- Academy of Finland (AKA) [134117, 134117] Funding Source: Academy of Finland (AKA)
- Medical Research Council [G0801059, G0700785] Funding Source: researchfish
- MRC [G0801059, G0700785] Funding Source: UKRI
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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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