Cell Press, Cell Reports, 5(10), p. 833-839, 2015
DOI: 10.1016/j.celrep.2015.01.016
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Genomic structural variations (SVs) are large-scale structural differences in the genomic DNA ranging in size from a few kilobases to entire chromosomes. SVs may be unbalanced as in deletions, duplications, and insertions or balanced as in inversions and translocations or a combination thereof. SVs contribute to a large extent to the variability of our genome and are often associated with disease (Stankiewicz and Lupski, 2010). When occurring within the coding sequence of genes, they can affect the protein sequence and thereby protein function or stability. When encompassing one or several coding units, deletions or duplications lead to changes in gene dosage. Furthermore, it was shown that SVs could interfere with gene regulation by disrupting genomic architecture necessary for proper enhancer-promoter interactions. Such rearrangements can result in loss of WT interactions and/or ectopic enhancer-promoter interactions, thereby resulting in gene misexpression (Montavon et al., 2012, Spielmann et al., 2012 and Spielmann and Mundlos, 2013). To discriminate between these multiple effects and to study their complex molecular pathology in vivo modeling of SVs is required.