Today - five years after the inception of the DECIPHER database - researchers have published a report that reveals the developing role of the database in revolutionising both clinical practice and genetic research.
The report explores the growing benefits of DECIPHER for researchers, clinicians and patients - highlighting how the data, provided by around 100 centres and shared openly worldwide, can benefit all three groups.
DECIPHER - the Database of Chromosomal Imbalance and Phenotype in Humans using Ensembl Resources - is hosted at the Wellcome Trust Sanger Institute. It was established in 2004 to catalogue submicroscopic structural duplications, deletions and rearrangements in the genome - called copy number variants (CNVs) - and to uncover their possible role in disease.
"The first comprehensive map of human copy number variation was produced just three years ago, changing our understanding of human genetics" explains Nigel Carter, a lead member of the DECIPHER team from the Wellcome Trust Sanger Institute. "Since then, over 10,000 CNVs have been found, covering about 5 per cent of the human genome. This rate of advance has been remarkable: using new technologies, we are able to uncover the smaller, elusive variants at a 50 fold-higher resolution. But the pivotal role that DECIPHER plays is in looking at how these variants affect human health."
The problem researchers face is that while many CNVs initially appear to have no visible effect on individual health, others appear to have minor effects, and some are harmful. What DECIPHER helps clinicians to do is to evaluate CNVs and determine whether or not they are linked to the patient's problems. In some cases, the findings are novel or have been observed only a handful of times before. With consent from the patient, data can be shared worldwide and clusters of people with overlapping genetic rearrangements can be identified.
By looking at genetic information first in an unbiased and less subjective manner, recurrent genetic changes can be found, researchers can then seek matching symptoms. This reverses the traditional practice of identification where researchers would move from individuals with shared symptoms back to a chromosomal cause and is particularly helpful for conditions such as learning disability and congenital disorders which have a large number of different genetic causes.
"We need new ways to uncover those rearrangements that cause human disease. But we must also be wary of dismissing CNVs if they appear to have no physical effect," says Charles Lee, an Associate Professor at Harvard Medical School and a Clinical Cytogeneticist at Brigham and Women's Hospital in Boston, USA. "For example, there may be variants that only affect people with a specific genetic makeup; or sometimes specific combinations of variants may result in pathology."