At the opposite site of DGV (the Database of Genomic Variants, which contains only not pathogenic variations), there is DECIPHER, a useful database to retrieve pathogenic and plausibly pathogenic structural variations in humans.
DECIPHER is an open-source database which contains data about a large amount of submicroscopic structural DNA variations (microdeletions, microduplications and other rearrangements) which have been detected in about 25,000 affected humans. Notably, DECIPHER contains also some single nucletoide variations. The variations are currently mapped according to the GRCh37 human assembly and can be interrogated either in the native DECIPHER browser or in the UCSC Genome Browser and Ensembl browser (indeed the acronym stays for Database of Chromosomal Imbalance and Phenotype in Humans using Ensembl Resources).
The listing of variants
One of the good things of the last years is the developing of more intuitive interfaces for several bioinformatics tools and DECIPHER is luckily no exception. When typing the gene name we get a page with all structural variations including this gene. Some key information on this page are: 1. DECIPHER entry ID, 2. chromosome, 3. chromosomal positions (i.e. start and end of the variation according to the genomic nomenclature), 4. size of the variation (deducible also from 3) and 5. type of variation (gain or loss of genomic material; see also image below). For some entries we also get a summary of the phenotypic characteristic of the patient.
The Genoverse browser
By clicking on any entry of the list we are prompted to the map of the so called Genoverse browser, which, at first sight, might appear a bit crowded, but its interpretation is not very difficult indeed. Here below an example about a deletion encompassing the entire LRRK2 gene and more.
Some key elements which are not very intuitive at the beginning are:
- the Gene Legend bar, with its “% HI ranges“. HI stays for HaploInsufficiency, wherein a single functional copy of a gene is insufficient to maintain normal function and is a major cause of dominant disease. High ranks (e.g. 0-10%) indicate a gene is more likely to exhibit haploinsufficiency, low ranks (e.g. 90-100%) indicate a gene is more likely to NOT exhibit haploinsufficiency.
- the Morbid Genes: these are actually the genes which are linked to a morbid entry (i.e. a disease entry) in OMIM.
Breda Genetics srl and DECIPHER
Since single nucleotide variations are still very few, DECIPHER cannot be used as a comprehensive tool for the interpretation of all sequencing data, yet it is very helpful in the interpretation of large deletions/duplications and other submicroscopic genomic rearrangements. We therefore consistently refer to DECIPHER whenever reporting about CGH array or our EXOME D analyses (clinical exome sequencing plus deletion/duplication testing across the entire genome – all by NGS).