Nature Reviews Genetics has a review of the emerging evidence for massive amounts of structural variation in the human genome.
The first wave of information from the analysis of the human genome revealed SNPs to be the main source of genetic and phenotypic human variation. However, the advent of genome-scanning technologies has now uncovered an unexpectedly large extent of what we term ‘structural variation’ in the human genome. This comprises microscopic and, more commonly, submicroscopic variants, which include deletions, duplications and large-scale copy-number variants – collectively termed copy-number variants or copy-number polymorphisms – as well as insertions, inversions and translocations. Rapidly accumulating evidence indicates that structural variants can comprise millions of nucleotides of heterogeneity within every genome, and are likely to make an important contribution to human diversity and disease susceptibility.
* Structural variants in the human genome include cytogenetically detectable and submicroscopic deletions, duplications, large-scale copy-number variants, inversions and translocations.
* The ability to detect and characterize structural variants in the 1-kb to 3-Mb size range in a robust manner across the genome has not been possible until recently.
* New developments in genome-scanning technologies and computational methodologies, and the availability of a reference sequence for comparison, have made possible the large-scale discovery of structural variants.
* Many studies are revealing that the total content of structural variants in the human genome could equal or exceed that of SNPs.
* Structural variants often coincide with low-copy repeat DNA (also called segmental duplications), as these highly related sequences are more likely to undergo non-allelic recombination and subsequent rearrangement.
* Structural variation in the genome can directly or indirectly influence gene dosage through different mechanisms, and therefore influence phenotypic variation and disease.
* The cataloguing of structural variants and their frequencies in populations will be important for disease-mapping studies and for proper interpretation of clinical diagnostic-testing data.