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Title: Influence of ATM-mediated DNA damage response on genomic variation in human induced pluripotent stem cells (Affymetrix CNV)      
keywords:
Variation
ID:
PRJNA313311
description:
Genome instability is a potential limitation to the research and therapeutic application of induced pluripotent stem cells (iPSCs). Observed genomic variations reflect the combined activities of DNA damage, cellular DNA damage response (DDR), and selection pressure in culture. To understand the contribution of DDR on the distribution of copy number variations (CNVs) in iPSCs, we mapped CNVs of iPSCs with mutations in the central DDR gene ATM onto genome organization landscapes defined by genome-wide replication timing profiles. We show that following reprogramming the early and late replicating genome is differentially affected by CNVs in ATM deficient iPSCs relative to wild type iPSCs. Specifically, the early replicating regions had increased CNV losses during retroviral reprogramming. This differential CNV distribution was not present after later passage or after episomal reprogramming. Comparison of different reprogramming methods in the setting of defective DNA damage response reveals unique vulnerability of early replicating open chromatin to retroviral vectors. Overall design: We isolated genomic DNA from Ataxia-telangiectasia (A-T) iPSC cells derived from patient fibroblasts virus and episomal vectors, coresponding fibroblasts, normal human fibroblast derived iPSCcells, for hybridization to the Affymetrix Genome-Wide Human SNP 6.0 Array.
accesstypes:
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landingpage: http://www.ncbi.nlm.nih.gov/bioproject/PRJNA313311
authentication:
none
authorization:
none
ID:
pmid:26935587
name:
Homo sapiens
ncbiID:
ncbitax:9606
abbreviation:
NCBI
homePage: http://www.ncbi.nlm.nih.gov
ID:
SCR:006472
name:
National Center for Biotechnology Information
homePage: http://www.ncbi.nlm.nih.gov/bioproject
ID:
SCR:004801
name:
NCBI BioProject
  • P01 GM085354/GM/NIGMS NIH HHS/United States

  • R01 GM083337/GM/NIGMS NIH HHS/United States

  • R21 CA161666/CA/NCI NIH HHS/United States

  • R00 HD061981/HD/NICHD NIH HHS/United States

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