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Deletion of ultraconserved elements yields viable mice.

PLoS biology | Sep 20, 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

Mesh terms: Animals | Conserved Sequence | Fertility | Genome | Mice | Phenotype | Sequence Deletion | Survival

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Associated grants

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

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GenBank

NIH genetic sequence database that provides an 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 the web-based BankIt or standalone Sequin programs, and GenBank staff assigns accession numbers upon data receipt. It is part of the International Nucleotide Sequence Database Collaboration and daily data exchange with the European Nucleotide Archive (ENA) and the DNA Data Bank of Japan (DDBJ) ensures worldwide coverage. GenBank is accessible through the NCBI Entrez retrieval system, which integrates data from the major DNA and protein sequence databases along with taxonomy, genome, mapping, protein structure and domain information, and the biomedical journal literature via PubMed. BLAST provides sequence similarity searches of GenBank and other sequence databases. Complete bimonthly releases and daily updates of the GenBank database are available by FTP.

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GenePaint.org

A digital atlas of gene expression patterns in the 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 were labeled using non radioactive in situ hybridization with riboprobes and annotated for level of gene expression (not detected, weak, medium, strong) and pattern (ubiquitous, regional, scattered). 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 a virtual microscope tool that enables zooming into images down to cellular resolution.

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