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Title: Deletion of ultraconserved elements yields viable mice

Abstract

Ultraconserved elements have been suggested to retainextended perfect sequence identity between the human, mouse, and ratgenomes due to essential functional properties. To investigate thenecessities of these elements in vivo, we removed four non-codingultraconserved elements (ranging in length from 222 to 731 base pairs)from the mouse genome. To maximize the likelihood of observing aphenotype, we chose to delete elements that function as enhancers in amouse transgenic assay and that are near genes that exhibit markedphenotypes both when completely inactivated in the mouse as well as whentheir expression is altered due to other genomic modifications.Remarkably, all four resulting lines of mice lacking these ultraconservedelements were viable and fertile, and failed to reveal any criticalabnormalities 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 where genes in proximityto the investigated elements had been altered, also failed to revealnotable abnormalities. These results, while not inclusive of all thepossible phenotypic impact of the deleted sequences, indicate thatextreme sequence constraint does not necessarily reflect crucialfunctions required for viability.

Authors:
; ; ; ; ; ;
Publication Date:
Research Org.:
Ernest Orlando Lawrence Berkeley NationalLaboratory, Berkeley, CA (US)
Sponsoring Org.:
USDOE Director, Office of Science; National Institutes ofHealth
OSTI Identifier:
925538
Report Number(s):
LBNL-63263
R&D Project: GHPG6D; TRN: US200809%%795
DOE Contract Number:  
DE-AC02-05CH11231; NIH:U1HL66681B
Resource Type:
Journal Article
Resource Relation:
Journal Name: PLoS Biology; Journal Volume: 5; Journal Issue: 9; Related Information: Journal Publication Date: 09/2007
Country of Publication:
United States
Language:
English
Subject:
60; FUNCTIONALS; GENES; IN VIVO; METABOLISM; MICE; MODIFICATIONS; PATHOLOGY; PHENOTYPE; SCREENS; VIABILITY

Citation Formats

Ahituv, Nadav, Zhu, Yiwen, Visel, Axel, Holt, Amy, Afzal, Veena, Pennacchio, Len A., and Rubin, Edward M. Deletion of ultraconserved elements yields viable mice. United States: N. p., 2007. Web. doi:10.1371/journal.pbio.0050234.
Ahituv, Nadav, Zhu, Yiwen, Visel, Axel, Holt, Amy, Afzal, Veena, Pennacchio, Len A., & Rubin, Edward M. Deletion of ultraconserved elements yields viable mice. United States. doi:10.1371/journal.pbio.0050234.
Ahituv, Nadav, Zhu, Yiwen, Visel, Axel, Holt, Amy, Afzal, Veena, Pennacchio, Len A., and Rubin, Edward M. Sun . "Deletion of ultraconserved elements yields viable mice". United States. doi:10.1371/journal.pbio.0050234. https://www.osti.gov/servlets/purl/925538.
@article{osti_925538,
title = {Deletion of ultraconserved elements yields viable mice},
author = {Ahituv, Nadav and Zhu, Yiwen and Visel, Axel and Holt, Amy and Afzal, Veena and Pennacchio, Len A. and Rubin, Edward M.},
abstractNote = {Ultraconserved elements have been suggested to retainextended perfect sequence identity between the human, mouse, and ratgenomes due to essential functional properties. To investigate thenecessities of these elements in vivo, we removed four non-codingultraconserved elements (ranging in length from 222 to 731 base pairs)from the mouse genome. To maximize the likelihood of observing aphenotype, we chose to delete elements that function as enhancers in amouse transgenic assay and that are near genes that exhibit markedphenotypes both when completely inactivated in the mouse as well as whentheir expression is altered due to other genomic modifications.Remarkably, all four resulting lines of mice lacking these ultraconservedelements were viable and fertile, and failed to reveal any criticalabnormalities 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 where genes in proximityto the investigated elements had been altered, also failed to revealnotable abnormalities. These results, while not inclusive of all thepossible phenotypic impact of the deleted sequences, indicate thatextreme sequence constraint does not necessarily reflect crucialfunctions required for viability.},
doi = {10.1371/journal.pbio.0050234},
journal = {PLoS Biology},
number = 9,
volume = 5,
place = {United States},
year = {Sun Jul 15 00:00:00 EDT 2007},
month = {Sun Jul 15 00:00:00 EDT 2007}
}