Genome recombination on demand

Abstract

The human genome consists of more than 3 billion base pairs, among which only 1% encode proteins. These coding regions are small islands within a sea of noncoding and repetitive sequences. It remains unclear which DNA has a function or regulatory role and what the functional relevance of such genome architecture is. Advances in genome editing and functional genomics have facilitated the systematic interrogation of gene sequence and function. Yet there is little understanding of how gene order, orientation, and spacing affect gene expression and encode biological functions. On pages 487 and 488 of this issue, Koeppel et al. (1) and Pinglay et al. (2), respectively, present approaches for generating large genome rearrangements in mammalian cells at unprecedented scale. These technologies pave the way for largescale functional analyses of genome organization, structural variants, noncoding DNA, and the design of mammalian cell lines with evolved properties.