Structural variations (SVs), including chromosomal aberrations, are changes to the structure or number of chromosomes. Chromosomes are long DNA molecules containing the genetic material of living organisms. There can be extra or missing chromosomes, or chromosomes that have different types of rearrangements resulting in gains and losses of DNA, copy number changes, and balanced shifts in position. Any of these SVs can disrupt the normal function of a gene and contribute to the development of a broad range of genetic diseases and cancer. Unlike single nucleotide variants (SNVs) or small deletions and duplications (indels), SVs can range in size from a few hundred base pairs to thousands or millions of base pairs of DNA. Traditionally, SVs have been identified by karyotyping, fluorescence in situ hybridization (FISH), and chromosomal microarray (CMA).
Optical genome mapping (OGM) with Bionano genome mapping systems can identify all classes of structural variation by observing changes in label spacing and comparisons of order, position, and orientation of label patterns. Tab through the image carousel below to see how each type of SV is visualized with OGM.
Deletions result in a loss of genetic material. A decreased spacing of labels, with or without loss of the labels themselves, is evidence of a deletion.
Insertions result in a gain of genetic material. Label spacing that increases with or without additional labels detected point to inserted sequences.
Translocations are rearrangements that can occur within chromosomes (intrachromosomal) or between chromosomes (interchromosomal). Genome maps aligning partially with two or more different chromosomes or genomic locations indicate translocations.
Inversions result within a single chromosome and can either include the centromere (pericentric) or be confined to one arm (paracentric). When label patterns are inverted relative to the reference, an inversion is called.
Repeat expansions and contractions are dynamic mutations that occur when specific sequence motif changes repeat size throughout successive generations. Like deletions and insertions, expansions or contractions of tandem arrays or segmental duplications can be identified by changes in label spacing.
1. Perry GH, Yang F, Marques-Bonet T, et al. Copy number variation and evolution in humans and chimpanzees. Genome Res. 2008;18(11):1698-1710. doi:10.1101/gr.082016.108
2. Weischenfeldt J, Symmons O, Spitz F, Korbel JO. Phenotypic impact of genomic structural variation: insights from and for human disease. Nat Rev Genet. 2013;14(2):125-138. doi:10.1038/nrg3373
3. Pang AW, MacDonald JR, Pinto D, et al. Towards a comprehensive structural variation map of an individual human genome. Genome Biol. 2010;11(5):R52. doi:10.1186/gb-2010-11-5-r52
4. Sebat J, Lakshmi B, Malhotra D, et al. Strong association of de novo copy number mutations with autism. Science. 2007;316(5823):445-449. doi:10.1126/science.1138659
5. Beroukhim R, Mermel CH, Porter D, et al. The landscape of somatic copy-number alteration across human cancers. Nature. 2010;463(7283):899-905. doi:10.1038/nature08822
6. Talkowski ME, Rosenfeld JA, Blumenthal I, et al. Sequencing chromosomal abnormalities reveals neurodevelopmental loci that confer risk across diagnostic boundaries. Cell. 2012;149(3):525-537. doi:10.1016/j.cell.2012.03.028
7. Collins RL, Brand H, Karczewski KJ, et al. A structural variation reference for medical and population genetics [published correction appears in Nature. 2021 Feb;590(7846):E55]. Nature. 2020;581(7809):444-451. doi:10.1038/s41586-020-2287-8
8. Chiang C, Scott AJ, Davis JR, et al. The impact of structural variation on human gene expression. Nat Genet. 2017;49(5):692-699. doi:10.1038/ng.3834
9. Manolio TA, Collins FS, Cox NJ, et al. Finding the missing heritability of complex diseases. Nature. 2009;461(7265):747-753. doi:10.1038/nature08494