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Array-based comparative genomic hybridization study of human embryonic stem cell lines

ABSTRACT: G-banding of human embryonic stem cells (hESC) has proved their predisposition to aneuploidy of chromosomes 12, 17 and X. Now, using array-based comparative genomic hybridization, we find that hESC also accumulate other recurrent chromosomal abnormalities, such as duplications of stemness genes, submicroscopic instability of 20q11.21 and the appearance of a derivative chromosome 18. Keywords: comparative genomic hybridization, genomic integrity of human embryonic stem cells

ORGANISM(S): Homo sapiens

PROVIDER: GSE13422 | GEO | 2008/11/04

SECONDARY ACCESSION(S): PRJNA110075

REPOSITORIES: GEO

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Array-based comparative genomic hybridization study of human embryonic stem cell lines

Project description:G-banding of human embryonic stem cells (hESC) has proved their predisposition to aneuploidy of chromosomes 12, 17 and X. Now, using array-based comparative genomic hybridization, we find that hESC also accumulate other recurrent chromosomal abnormalities, such as duplications of stemness genes, submicroscopic instability of 20q11.21 and the appearance of a derivative chromosome 18. Keywords: comparative genomic hybridization, genomic integrity of human embryonic stem cells Array-based comparative genomic hybridization was performed on 48 DNA samples from 17 human embryonic stem cell lines, all cultured in our laboratory under the same conditions. All lines were hybridized against DNA obtained from peripheral blood from donors with a known normal karyotype. No replicates were done from the same DNA sample, but, whenever possible the same stem cell line was analysed at later passages. All detected abnormalities were confirmed by FISH and/or G-banding.

2010-05-17 | E-GEOD-13422 | biostudies-arrayexpress

16p13 aberrations predispose to autism and MR

Project description:Autism and mental retardation (MR) are often associated, suggesting that these conditions are etiologically related. Recently, array-based comparative genomic hybridization (array CGH) has identified submicroscopic deletions and duplications as a common cause of MR. This prompted us to search for such genomic imbalances in autism and related disorders. Here we describe a 1.5 Mb duplication on chromosome 16p13.1, found in four autistic male patients from three families and several variably affected and unaffected relatives. A deletion of the same interval was identified in three unrelated patients with MR and other clinical abnormalities. Duplications and deletions of this interval have not been described before, neither as copy number variants in the Database of Genomic Variants nor in >600 individuals from other cohorts examined by high resolution array CGH in our laboratory. Thus, this is the first description of a recurrent genomic imbalance predisposing to autism and/or MR. Keywords: array CGH

2007-05-22 | GSE6225 | GEO

The genomic landscape of colitis-associated colorectal carcinomas is dominated by TP53 mutations, aneuploidy and gains of chromosome arm 5p

Project description:Ulcerative colitis associated colorectal tumors were characterized by array-based comparative genomic hybridization to elucidate chromosomal aneuploidy patterns.

2022-02-01 | GSE156076 | GEO

Comparative genomic hybridization of human embryonic stem cell lines deposited in the National Stem Cell Bank

Project description:The Purpose of this series of experiments is to identify copy number variations, duplications, and deletions in human embryonic stem (hES) cell lines deposited to the National Stem Cell bank and reveal the difference between different hES cell lines. CGH can achieve these aims at higher resolution. Keywords: comparative genomic hybridization

2007-10-16 | GSE9313 | GEO

Human ES cells reveal recurrent genomic instability at 20q11.21

Project description:By analyzing five human embryonic stem (hES) cell lines over long-term culture, we detected a recurrent genomic instability in the human genome. An amplification of 2.5â4.6 Mb at 20q11.21, encompassing about 23 genes in common, appeared in four cell lines of different origins. This amplification, which has been associated with oncogenic transformation, may provide a selective advantage to hES cells in culture Array-based comparative genomic hybridization, was performed on genomic DNA samples from different human embryonic stem cell lines, all cultured in our laboratory under the same conditions. VUB05-HD is an hES cell line carrying the Huntingtin mutant gene H1, H9, SA01, and VUB01 are various hES cell lines GSM341552 and GSM341553: SNP analysis GSM341589 to GSM341669: CGH analysis

2010-05-16 | E-GEOD-13565 | biostudies-arrayexpress

Gene expression comparison between human embryonic stem cell lines with a normal karyotype and after acquiring a duplication of 20q11.21

Project description:Since the introduction of high-resolution molecular cytogenetic methods for the screening for chromosomal abnormalities in human embryonic stem cells (hESC), numerous laboratories worldwide have reported the gain of 20q11.21 as a recurrent mutation. Recently, in a large joint study, the International Stem Cell Initiative (ISCI) screened 125 hESC lines worldwide and found this aberration in over 20% of the lines. In our laboratory, we found an increased copy number of 20q11.21 in four hESC lines, VUB01, VUB02, VUB03 and VUB07. We first carried out Affymetrix HG-U133-Plus2 gene-expression microarray analysis of pairs of the mutant and wild type sublines. We identified a small group of very significantly deregulated genes, but none of them were located in the region of duplication. Validation of these results by qRT-PCR revealed that CHCHD2 and TRPC6 were most consistently deregulated.

2019-06-12 | GSE41439 | GEO

Non-clonal mosaicism in human somatic and embryonic stem cells revealed by single-cell array-based copy-number variation analysis

Project description:Although it is known that cultured human cells acquire copy number variations over time, little is known about the mutation frequency in individual cells. Here we describe that human somatic and embryonic stem cell cultures show significant fractions of cells carrying unique chromosomal abnormalities, forming a non-clonal genetic mosaic. We studied 85 human single cells by array-based comparative genomic hybridisation and found that 14-31% of hESC and 8-26% of somatic cells are chromosomally abnormal. Remarkably, only 2 cells showed full-chromosome aneuploidy, while 93% of detected abnormalities were segmental, most of them telomere-spanning. Furthermore, fluorescent in situ hybridisation confirmed this finding and revealed an increased instability of the subtelomeric regions in hESC as compared to somatic cells.

2014-06-24 | GSE51126 | GEO

Characterization of human embryonic stem cells with features of neoplastic progression

Project description:Cultured human embryonic stem (hES) cells can acquire genetic and epigenetic changes that make them vulnerable to transformation. As hES cells with cancer-cell characteristics share properties with normal hES cells, such as self-renewal, teratoma formation and the expression of pluripotency markers, they may be misconstrued as superior hES cells with enhanced âstemnessâ. We characterize two variant hES cell lines (v-hESC-1 and v-hESC-2) that express pluripotency markers at high levels and do not harbor chromosomal abnormalities by standard cytogenetic measures. We show that the two lines possess some features of neoplastic progression, including a high proliferative capacity, growth-factor independence, a 9- to 20-fold increase in frequency of tumor initiating cells, niche independence and aberrant lineage specification, although they are not malignant. Array comparative genomic hybridization revealed an amplification at 20q11.1-11.2 in v-hESC-1 and a deletion at 5q34a-5q34b;5q3 and a mosaic gain of chromosome 12 in v-hESC-2. These results emphasize the need for functional characterization to distinguish partially transformed and normal hES cells. Custom oligonucleotide array gene expression analysis was performed on total RNA from low passage normal and variant human embryonic stem cell (hESC) lines, all cultured in our laboratory under the same conditions. Furthermore, array-based comparative genomic hybridization was also performed on the normal and variant hESC lines. v-hESC-1 and v-hESC-2 represent two independent lines that display neoplastic characteristics with distinctive copy number alterations. v-hESC-1_A2B5 represents neural precursor cultures differentiated from variant hES cells. GSM349016-GSM349022: Gene expression analysis GSM351500-GSM351511: aCGH analysis

2010-06-24 | E-GEOD-13995 | biostudies-arrayexpress

CGH analysis of Candida albicans strains

Project description:Aneuploidy and the evolution of aneuploid karyotypes of Candida albicans strains was identified using aCGH. Whole chromosome and segmental aneuploidies, (specifically on the left arm of chromosome 5 - shown to be due to isochromosome formation) are associated with the appearance of resistance to the antifungal drug fluconazole. Keywords: Comparative Genomic Hybridization

2006-06-30 | GSE4995 | GEO

Expression data from undifferentiated human induced pluripotent stem cells

Project description:Due to their somatic cell origin, human induced pluripotent stem cells (HiPSCs) are assumed to carry a normal diploid genome, and adaptive chromosomal aberrations have not been fully evaluated. Here, we analyzed the chromosomal integrity of 66 HiPSC and 38 human embryonic stem cell (HESC) samples from 18 different studies by global gene expression meta-analysis. We report identification of a substantial number of cell lines carrying full and partial chromosomal aberrations, half of which were validated at the DNA level. Several aberrations resulted from culture adaptation, and others are suspected to originate from the parent somatic cell. Our classification revealed a third type of aneuploidy already evident in early passage HiPSCs, suggesting considerable selective pressure during the reprogramming process. The analysis indicated high incidence of chromosome 12 duplications, resulting in significant enrichment for cell cycle related genes. Such aneuploidy may limit the differentiation capacity and increase the tumorigenicity of HiPSCs.

2010-04-09 | GSE21243 | GEO

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