Megabase deletions of gene deserts result in viable mice.

Journal:

Nature 2004 Oct

Authors:

Nóbrega MA, Zhu Y, Plajzer-Frick I, Afzal V, Rubin EM

Abstract

The functional importance of the roughly 98% of mammalian genomes not corresponding to protein coding sequences remains largely undetermined. Here we show that some large-scale deletions of the non-coding DNA referred to as gene deserts 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
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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.[less]

Mesh Headings:

Animals, Chromosome Deletion, Chromosomes, Mammalian, Conserved Sequence, Female, Gene Expression Profiling, Genes, Essential, Genome, Homozygote, Humans, Longevity, Male, Mice, Mice, Mutant Strains, Mice, Transgenic, Phenotype, Reproduction, Sequence Deletion