High-resolution DNA Analysis of Human Embryonic Stem Cell Lines Reveals Culture-induced Copy Number Changes and Loss of Heterozygosity

Overview

Journal Nat Biotechnol

Specialty Biotechnology

Date 2010 Mar 31

PMID 20351689

Citations 139

Authors

Elisa Narva

Reija Autio

Nelly Rahkonen

Lingjia Kong

Neil Harrison

Danny Kitsberg

Lodovica Borghese

Joseph Itskovitz-Eldor

Omid Rasool

Petr Dvorak

Outi Hovatta

Timo Otonkoski

Timo Tuuri

Wei Cui

Oliver Brustle

Duncan Baker

Edna Maltby

Harry D Moore

Nissim Benvenisty

Peter W Andrews

Olli Yli-Harja

Riitta Lahesmaa

Affiliations

Soon will be listed here.

Abstract

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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