Letters to Nature

Nature 431, 988-993 (21 October 2004) | doi:10.1038/nature03022; Received 2 June 2004; Accepted 8 September 2004

Megabase deletions of gene deserts result in viable mice

Marcelo A. Nóbrega2, Yiwen Zhu2, Ingrid Plajzer-Frick, Veena Afzal & Edward M. Rubin

  1. DOE Joint Genome Institute Walnut Creek, California 94598, USA, and Genomics Division Lawrence Berkeley National Laboratory Berkeley, California 94720, USA
  2. These authors contributed equally to this work

Correspondence to: Edward M. Rubin Correspondence and requests for materials should be addressed to E.M.R. (Email: emrubin@lbl.gov).

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.

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