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Deletion of ultraconserved elements yields viable mice.

PLoS biology | 2007

Ultraconserved elements have been suggested to retain extended perfect sequence identity between the human, mouse, and rat genomes due to essential functional properties. To investigate the necessities of these elements in vivo, we removed four noncoding ultraconserved elements (ranging in length from 222 to 731 base pairs) from the mouse genome. To maximize the likelihood of observing a phenotype, we chose to delete elements that function as enhancers in a mouse transgenic assay and that are near genes that exhibit marked phenotypes both when completely inactivated in the mouse and when their expression is altered due to other genomic modifications. Remarkably, all four resulting lines of mice lacking these ultraconserved elements were viable and fertile, and failed to reveal any critical abnormalities when assayed for a variety of phenotypes including growth, longevity, pathology, and metabolism. In addition, more targeted screens, informed by the abnormalities observed in mice in which genes in proximity to the investigated elements had been altered, also failed to reveal notable abnormalities. These results, while not inclusive of all the possible phenotypic impact of the deleted sequences, indicate that extreme sequence constraint does not necessarily reflect crucial functions required for viability.

Pubmed ID: 17803355 RIS Download

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Associated grants

  • Agency: NHGRI NIH HHS, United States
    Id: R01 HG003988
  • Agency: NHLBI NIH HHS, United States
    Id: HL066681
  • Agency: NHGRI NIH HHS, United States
    Id: HG003988
  • Agency: NHGRI NIH HHS, United States
    Id: R01 HG003988-02
  • Agency: NHLBI NIH HHS, United States
    Id: U01 HL066681

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GenBank (tool)

RRID:SCR_002760

NIH genetic sequence database that provides annotated collection of all publicly available DNA sequences for almost 280 000 formally described species (Jan 2014) .These sequences are obtained primarily through submissions from individual laboratories and batch submissions from large-scale sequencing projects, including whole-genome shotgun (WGS) and environmental sampling projects. Most submissions are made using web-based BankIt or standalone Sequin programs, and GenBank staff assigns accession numbers upon data receipt. It is part of International Nucleotide Sequence Database Collaboration and daily data exchange with European Nucleotide Archive (ENA) and DNA Data Bank of Japan (DDBJ) ensures worldwide coverage. GenBank is accessible through NCBI Entrez retrieval system, which integrates data from major DNA and protein sequence databases along with taxonomy, genome, mapping, protein structure and domain information, and biomedical journal literature via PubMed. BLAST provides sequence similarity searches of GenBank and other sequence databases. Complete bimonthly releases and daily updates of GenBank database are available by FTP.

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GenePaint (tool)

RRID:SCR_003015

Digital atlas of gene expression patterns in developing and adult mouse. Several reference atlases are also available through this site. Expression patterns are determined by non-radioactive in situ hybridization on serial tissue sections. Sections are available from several developmental ages: E10.5, E14.5 (whole embryos), E15.5, P7 and P56 (brains only). To retrieve expression patterns, search by gene name, site of expression, GenBank accession number or sequence homology. For viewing expression patterns, GenePaint.org features virtual microscope tool that enables zooming into images down to cellular resolution.

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C57BL/6J (tool)

RRID:IMSR_JAX:000664

Mus musculus with name C57BL/6J from IMSR.

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