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Genome-wide gene amplification during differentiation of neural progenitor cells in vitro.

Fischer U, Keller A, Voss M, Backes C, Welter C, Meese E - PLoS ONE (2012)

Bottom Line: We used array-CGH (comparative genomic hybridization) and FISH (fluorescence in situ hybridization) to discover gene amplifications during in vitro differentiation of human neural progenitor cells.Here we report a complex gene amplification pattern two and five days after induction of differentiation of human neural progenitor cells.Gene amplifications in normal human cells as physiological process has not been reported yet and may bear resemblance to developmental gene amplifications in amphibians and insects.

View Article: PubMed Central - PubMed

Affiliation: Department of Human Genetics, Saarland University, Homburg/Saar, Germany. ulrike.fischer@uks.eu

ABSTRACT
DNA sequence amplification is a phenomenon that occurs predictably at defined stages during normal development in some organisms. Developmental gene amplification was first described in amphibians during gametogenesis and has not yet been described in humans. To date gene amplification in humans is a hallmark of many tumors. We used array-CGH (comparative genomic hybridization) and FISH (fluorescence in situ hybridization) to discover gene amplifications during in vitro differentiation of human neural progenitor cells. Here we report a complex gene amplification pattern two and five days after induction of differentiation of human neural progenitor cells. We identified several amplified genes in neural progenitor cells that are known to be amplified in malignant tumors. There is also a striking overlap of amplified chromosomal regions between differentiating neural progenitor cells and malignant tumor cells derived from astrocytes. Gene amplifications in normal human cells as physiological process has not been reported yet and may bear resemblance to developmental gene amplifications in amphibians and insects.

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Correlation of gene content to chromosome region.The correlation is shown for human chromosome 16 with several amplified and one deleted region in NHNP cells after 5 d differentiation. The log2 ratio profile of the 10× window averaged data is presented at 25 kb resolution (A). Fused lasso analysis is performed using the same data points (B). GC repeats, gene content and banding pattern is shown as indicated by Ensembl genome browser (C). Both the log2 ratio profile and the fused lasso analysis indicate an overlap between amplifications and regions with high GC and gene content and an overlap between deletion and regions with low GC and gene content.
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pone-0037422-g005: Correlation of gene content to chromosome region.The correlation is shown for human chromosome 16 with several amplified and one deleted region in NHNP cells after 5 d differentiation. The log2 ratio profile of the 10× window averaged data is presented at 25 kb resolution (A). Fused lasso analysis is performed using the same data points (B). GC repeats, gene content and banding pattern is shown as indicated by Ensembl genome browser (C). Both the log2 ratio profile and the fused lasso analysis indicate an overlap between amplifications and regions with high GC and gene content and an overlap between deletion and regions with low GC and gene content.

Mentions: Analysis of these chromosome regions revealed hundreds of genes that were involved in this amplification process. Besides amplifications, we also detected deletions that were mainly localized in chromosome regions lacking genes or contain only few genes. In contrast, amplified chromosome regions mainly map within chromosome regions with a high gene density (Figure 5).


Genome-wide gene amplification during differentiation of neural progenitor cells in vitro.

Fischer U, Keller A, Voss M, Backes C, Welter C, Meese E - PLoS ONE (2012)

Correlation of gene content to chromosome region.The correlation is shown for human chromosome 16 with several amplified and one deleted region in NHNP cells after 5 d differentiation. The log2 ratio profile of the 10× window averaged data is presented at 25 kb resolution (A). Fused lasso analysis is performed using the same data points (B). GC repeats, gene content and banding pattern is shown as indicated by Ensembl genome browser (C). Both the log2 ratio profile and the fused lasso analysis indicate an overlap between amplifications and regions with high GC and gene content and an overlap between deletion and regions with low GC and gene content.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3351388&req=5

pone-0037422-g005: Correlation of gene content to chromosome region.The correlation is shown for human chromosome 16 with several amplified and one deleted region in NHNP cells after 5 d differentiation. The log2 ratio profile of the 10× window averaged data is presented at 25 kb resolution (A). Fused lasso analysis is performed using the same data points (B). GC repeats, gene content and banding pattern is shown as indicated by Ensembl genome browser (C). Both the log2 ratio profile and the fused lasso analysis indicate an overlap between amplifications and regions with high GC and gene content and an overlap between deletion and regions with low GC and gene content.
Mentions: Analysis of these chromosome regions revealed hundreds of genes that were involved in this amplification process. Besides amplifications, we also detected deletions that were mainly localized in chromosome regions lacking genes or contain only few genes. In contrast, amplified chromosome regions mainly map within chromosome regions with a high gene density (Figure 5).

Bottom Line: We used array-CGH (comparative genomic hybridization) and FISH (fluorescence in situ hybridization) to discover gene amplifications during in vitro differentiation of human neural progenitor cells.Here we report a complex gene amplification pattern two and five days after induction of differentiation of human neural progenitor cells.Gene amplifications in normal human cells as physiological process has not been reported yet and may bear resemblance to developmental gene amplifications in amphibians and insects.

View Article: PubMed Central - PubMed

Affiliation: Department of Human Genetics, Saarland University, Homburg/Saar, Germany. ulrike.fischer@uks.eu

ABSTRACT
DNA sequence amplification is a phenomenon that occurs predictably at defined stages during normal development in some organisms. Developmental gene amplification was first described in amphibians during gametogenesis and has not yet been described in humans. To date gene amplification in humans is a hallmark of many tumors. We used array-CGH (comparative genomic hybridization) and FISH (fluorescence in situ hybridization) to discover gene amplifications during in vitro differentiation of human neural progenitor cells. Here we report a complex gene amplification pattern two and five days after induction of differentiation of human neural progenitor cells. We identified several amplified genes in neural progenitor cells that are known to be amplified in malignant tumors. There is also a striking overlap of amplified chromosomal regions between differentiating neural progenitor cells and malignant tumor cells derived from astrocytes. Gene amplifications in normal human cells as physiological process has not been reported yet and may bear resemblance to developmental gene amplifications in amphibians and insects.

Show MeSH
Related in: MedlinePlus