Lawrence Berkeley National Laboratory
Megabase deletions of gene deserts result in viable mice
- Author(s): Nobrega, Marcelo A.
- Zhu, Yiwen
- Plajzer-Frick, Ingrid
- Afzal, Veena
- Rubin, Edward M.
- et al.
The functional importance of the approximately 98 percent of mammalian genomes not corresponding to protein coding sequences remain largely un-scrutinized 1. To test experimentally whether some extensive regions of non-coding DNA, referred to as gene deserts 2-4, contain critical functions essential for the viability of the organism, we deleted two large non-coding intervals, 1,511 kb and 845 kb in length, from the mouse genome. Viable mice homozygous for the deletions were generated and were indistinguishable from wild-type littermates with regards to morphology, reproductive fitness, growth, longevity and a variety of parameters assaying general homeostasis. Further in-depth analysis of the expression of genes bracketing the deletions revealed similar expression characteristics in homozygous deletion and wild-type mice. Together, the two deleted segments harbour 1,243 non-coding sequences conserved between humans and rodents (>100bp, 70 percent identity). These studies demonstrate that some large-scale deletions of non-coding DNA can be well tolerated by an organism, bringing into question the role of many human-mouse conserved sequences 5,6, and further supports the existence of potentially "disposable DNAi" in the genomes of mammals.