title: Copy number variant analysis of human embryonic stem cells.
abstract: Differences between individual DNA sequences provide the basis for human genetic variability. Forms of genetic variation include single-nucleotide polymorphisms, insertions/duplications, deletions, and inversions/translocations. The genome of human embryonic stem cells (hESCs) has been characterized mainly by karyotyping and comparative genomic hybridization (CGH), techniques whose relatively low resolution at 2-10 megabases (Mb) cannot accurately determine most copy number variability, which is estimated to involve 10%-20% of the genome. In this brief technical study, we examined HSF1 and HSF6 hESCs using array-comparative genomic hybridization (aCGH) to determine copy number variants (CNVs) as a higher-resolution method for characterizing hESCs. Our approach used five samples for each hESC line and showed four consistent CNVs for HSF1 and five consistent CNVs for HSF6. These consistent CNVs included amplifications and deletions that ranged in size from 20 kilobases to 1.48 megabases, involved seven different chromosomes, were both shared and unique between hESCs, and were maintained during neuronal stem/progenitor cell differentiation or drug selection. Thirty HSF1 and 40 HSF6 less consistently scored but still highly significant candidate CNVs were also identified. Overall, aCGH provides a promising approach for uniquely identifying hESCs and their derivatives and highlights a potential genomic source for distinct differentiation and functional potentials that lower-resolution karyotype and CGH techniques could miss. Disclosure of potential conflicts of interest is found at the end of this article.
authors: Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, California 90095-1732, USA.
authors: Hao
authors: H
authors: Wu
authors: Kevin J
authors: KJ
authors: Kim
authors: Kshama
authors: K
authors: Mehta
authors: Salvatore
authors: S
authors: Paxia
authors: Andrew
authors: A
authors: Sundstrom
authors: Thomas
authors: T
authors: Anantharaman
authors: Ali I
authors: AI
authors: Kuraishy
authors: Tri
authors: T
authors: Doan
authors: Jayati
authors: J
authors: Ghosh
authors: April D
authors: AD
authors: Pyle
authors: Amander
authors: A
authors: Clark
authors: William
authors: W
authors: Lowry
authors: Guoping
authors: G
authors: Fan
authors: Tim
authors: T
authors: Baxter
authors: Bud
authors: B
authors: Mishra
authors: Yi
authors: Y
authors: Sun
authors: Michael A
authors: MA
authors: Teitell
mesh_terms: D018929:Cell Culture Techniques; D002455:Cell Division / Q000235:genetics; D004247:DNA / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000502:physiology*; D014644:Genetic Variation; D015894:Genome, Human; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins / Q000235:genetics; D006801:Humans; D009474:Neurons / Q000166:cytology / Q000502:physiology; D009693:Nucleic Acid Hybridization / Q000379:methods; D016133:Polymerase Chain Reaction / Q000379:methods; D014157:Transcription Factors / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; C000619706:HSF1 protein, human; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; D014157:Transcription Factors; D004247:DNA