Megabase deletions of gene deserts result in viable mice

Marcelo A. Nóbrega, Yiwen Zhu, Ingrid Plajzer-Frick, Veena Afzal and Edward M. Rubin ()
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Marcelo A. Nóbrega: DOE Joint Genome Institute Walnut Creek
Yiwen Zhu: DOE Joint Genome Institute Walnut Creek
Ingrid Plajzer-Frick: DOE Joint Genome Institute Walnut Creek
Veena Afzal: DOE Joint Genome Institute Walnut Creek
Edward M. Rubin: DOE Joint Genome Institute Walnut Creek

Nature, 2004, vol. 431, issue 7011, 988-993

Abstract: Abstract The functional importance of the roughly 98% of mammalian genomes not corresponding to protein coding sequences remains largely undetermined1. Here we show that some large-scale deletions of the non-coding DNA referred to as gene deserts2,3,4 can be well tolerated by an organism. We deleted two large non-coding intervals, 1,511 kilobases and 845 kilobases in length, from the mouse genome. Viable mice homozygous for the deletions were generated and were indistinguishable from wild-type littermates with regard to morphology, reproductive fitness, growth, longevity and a variety of parameters assaying general homeostasis. Further detailed analysis of the expression of multiple genes bracketing the deletions revealed only minor expression differences in homozygous deletion and wild-type mice. Together, the two deleted segments harbour 1,243 non-coding sequences conserved between humans and rodents (more than 100 base pairs, 70% identity). Some of the deleted sequences might encode for functions unidentified in our screen; nonetheless, these studies further support the existence of potentially ‘disposable DNA’ in the genomes of mammals.

Date: 2004
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DOI: 10.1038/nature03022

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