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Deletion of ultraconserved elements yields viable mice
Nadav Ahituv1, Yiwen Zhu, Axel Visel
1Genomics Division, Lawrence Berkeley National Laboratory, Berkeley, California, United States of America.
Plos Biology
|September 7, 2007
Summary
Ultraconserved elements (UCEs) in the mouse genome were deleted to test their necessity. Surprisingly, mice lacking these highly conserved sequences showed no critical abnormalities, challenging assumptions about their essential functions.
Area of Science:
- Genomics
- Comparative genomics
- Evolutionary biology
Background:
- Ultraconserved elements (UCEs) exhibit high sequence identity across mammalian genomes.
- These elements are hypothesized to possess essential functional properties due to their conservation.
Purpose of the Study:
- To investigate the in vivo necessity of noncoding ultraconserved elements.
- To determine if extreme sequence constraint correlates with crucial functions for viability.
Main Methods:
- Deletion of four noncoding ultraconserved elements (222-731 bp) from the mouse genome.
- Selection of elements functioning as enhancers and located near genes with known phenotypes.
- Comprehensive phenotyping assays including growth, longevity, pathology, and metabolism.
Main Results:
- All four mouse lines lacking the targeted ultraconserved elements were viable and fertile.
- No critical abnormalities were detected in standard phenotyping assays.
- Targeted screens based on neighboring gene functions also revealed no significant abnormalities.
Conclusions:
- Extreme sequence constraint in ultraconserved elements does not necessarily imply essential functions for organismal viability.
- The functional significance of some ultraconserved elements may be context-dependent or redundant.
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