title: High-resolution DNA analysis of human embryonic stem cell lines reveals culture-induced copy number changes and loss of heterozygosity.
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.
authors.affiliation: Turku Centre for Biotechnology, University of Turku and Abo Akademi University, Turku, Finland. elisa.narva@btk.fi
authors.forename: Elisa
authors.initials: E
authors.lastname: Närvä
authors.forename: Reija
authors.initials: R
authors.lastname: Autio
authors.forename: Nelly
authors.initials: N
authors.lastname: Rahkonen
authors.forename: Lingjia
authors.initials: L
authors.lastname: Kong
authors.forename: Neil
authors.initials: N
authors.lastname: Harrison
authors.forename: Danny
authors.initials: D
authors.lastname: Kitsberg
authors.forename: Lodovica
authors.initials: L
authors.lastname: Borghese
authors.forename: Joseph
authors.initials: J
authors.lastname: Itskovitz-Eldor
authors.forename: Omid
authors.initials: O
authors.lastname: Rasool
authors.forename: Petr
authors.initials: P
authors.lastname: Dvorak
authors.forename: Outi
authors.initials: O
authors.lastname: Hovatta
authors.forename: Timo
authors.initials: T
authors.lastname: Otonkoski
authors.forename: Timo
authors.initials: T
authors.lastname: Tuuri
authors.forename: Wei
authors.initials: W
authors.lastname: Cui
authors.forename: Oliver
authors.initials: O
authors.lastname: Brüstle
authors.forename: Duncan
authors.initials: D
authors.lastname: Baker
authors.forename: Edna
authors.initials: E
authors.lastname: Maltby
authors.forename: Harry D
authors.initials: HD
authors.lastname: Moore
authors.forename: Nissim
authors.initials: N
authors.lastname: Benvenisty
authors.forename: Peter W
authors.initials: PW
authors.lastname: Andrews
authors.forename: Olli
authors.initials: O
authors.lastname: Yli-Harja
authors.forename: Riitta
authors.initials: R
authors.lastname: Lahesmaa
mesh_terms: D001483:Base Sequence; D018929:Cell Culture Techniques / Q000379:methods; D004247:DNA / Q000235:genetics*; D056915:DNA Copy Number Variations / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods*; D053595:Embryonic Stem Cells / Q000145:classification* / Q000502:physiology*; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D017422:Sequence Analysis, DNA / Q000379:methods*
chemical_list: D004247:DNA