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Genome-wide interrogation of Mammalian stem cell fate determinants by nested chromosome deletions.

PLoS genetics | 2010

Understanding the function of important DNA elements in mammalian stem cell genomes would be enhanced by the availability of deletion collections in which segmental haploidies are precisely characterized. Using a modified Cre-loxP-based system, we now report the creation and characterization of a collection of ∼1,300 independent embryonic stem cell (ESC) clones enriched for nested chromosomal deletions. Mapping experiments indicate that this collection spans over 25% of the mouse genome with good representative coverage of protein-coding genes, regulatory RNAs, and other non-coding sequences. This collection of clones was screened for in vitro defects in differentiation of ESC into embryoid bodies (EB). Several putative novel haploinsufficient regions, critical for EB development, were identified. Functional characterization of one of these regions, through BAC complementation, identified the ribosomal gene Rps14 as a novel haploinsufficient determinant of embryoid body formation. This new library of chromosomal deletions in ESC (DelES: http://bioinfo.iric.ca/deles) will serve as a unique resource for elucidation of novel protein-coding and non-coding regulators of ESC activity.

Pubmed ID: 21170304 RIS Download

Associated grants

  • Agency: Canadian Institutes of Health Research, Canada
    Id: MOP 82814

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This is a list of tools and resources that we have found mentioned in this publication.


International Gene Trap Consortium (tool)

RRID:SCR_002305

Consortium represents all publicly available gene trap cell lines, which are available on non-collaborative basis for nominal handling fees. Researchers can search and browse IGTC database for cell lines of interest using accession numbers or IDs, keywords, sequence data, tissue expression profiles and biological pathways, can find trapped genes of interest on IGTC website, and order cell lines for generation of mutant mice through blastocyst injection. Consortium members include: BayGenomics (USA), Centre for Modelling Human Disease (Toronto, Canada), Embryonic Stem Cell Database (University of Manitoba, Canada), Exchangeable Gene Trap Clones (Kumamoto University, Japan), German Gene Trap Consortium provider (Germany), Sanger Institute Gene Trap Resource (Cambridge, UK), Soriano Lab Gene Trap Resource (Mount Sinai School of Medicine, New York, USA), Texas Institute for Genomic Medicine - TIGM (USA), TIGEM-IRBM Gene Trap (Naples, Italy).

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Ensembl (tool)

RRID:SCR_002344

Collection of genome databases for vertebrates and other eukaryotic species with DNA and protein sequence search capabilities. Used to automatically annotate genome, integrate this annotation with other available biological data and make data publicly available via web. Ensembl tools include BLAST, BLAT, BioMart and the Variant Effect Predictor (VEP) for all supported species.

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miRBase (tool)

RRID:SCR_003152

Central online repository for microRNA nomenclature, sequence data, annotation and target prediction.Collection of published miRNA sequences and annotation.

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UCSC Genome Browser (tool)

RRID:SCR_005780

Portal to interactively visualize genomic data. Provides reference sequences and working draft assemblies for collection of genomes and access to ENCODE and Neanderthal projects. Includes collection of vertebrate and model organism assemblies and annotations, along with suite of tools for viewing, analyzing and downloading data.

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Knockout Mouse Project Repository (tool)

RRID:SCR_007318

Repository of mouse vectors, ES cells, mice, embryos, and sperm generated by NIH KOMP Mutagenesis Project. In addition, KOMP Repository offers services in support of KOMP products, including ES cell microinjection, vector cloning, post-insertional modification of cloned ES cells, cryopreservation, assisted reproduction techniques (IVF, ICSI) and mouse breeding, pathology services, phenotyping services, etc. KOMP Repository is final component of more than $50 million trans-NIH initiative to increase availability of genetically altered mice and related materials. The University of California, Davis (UC Davis) and Children''s Hospital Oakland Research Institute (CHORI) in Oakland, Calif., are collaborating to preserve, protect, and make available about 8,500 types of knockout mice and related products available to research community. Products are generated by two KOMP mutagenesis teams (CSD consortium and Regeneron Inc). All KOMP products generated by CSD consortium and Regeneron are available through KOMP Repository. Notice as of December 19, 2019: Materials from KOMP Repository have been deposited into MMRRC, including all mouse models and mouse embryonic stem cell lines. Eventually www.komp.org will be sunsetting, and IMSR will remove KOMP Repository listings, since they were double listed in MMRRC. MMRRC will contain the most accurate and up to date resource models.

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GoBean - a Java application for Gene Ontology enrichment analysis (tool)

RRID:SCR_005808

GoBean is a Java application for gene ontology enrichment analysis. It utilizes the NetBeans platform framework. Features * Graphical comparison of multiple enrichment analysis results * Versatile filter facility for focused analysis of enrichment results * Effective exploitation of the graphical/hierarchical structure of GO * Evidence code based association filtering * Supports local data files such as the ontology obo file and gene association files * Supports late enrichment methods and multiple testing corrections * Built-in ID conversion for common species using Ensembl biomart service Platform: Windows compatible, Mac OS X compatible, Linux compatible

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BLAT (tool)

RRID:SCR_011919

Software designed to quickly find sequences of 95% and greater similarity of length 25 bases or more.

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