DECIPHERing human disease

Database provides a key to unlock the causes of illnesses

The global distribution of DECIPHER consortium members. The Decipher consortium has around 100 members from countries across the globe
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. Since then, over 10,000 CNVs have been found, covering about five 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.”

Nigel Carter A lead member of the DECIPHER team from the Wellcome Trust Sanger Institute

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. 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.”

Charles Lee An Associate Professor at Harvard Medical School and a Clinical Cytogeneticist at Brigham and Women’s Hospital in Boston, USA

The report provides case studies in which DECIPHER played a pivotal role. In one example a four-year-old girl with symptoms of developmental delay and poor eye contact had a novel genetic finding and remained without a clear diagnosis. However, two new cases with similar structural variants were submitted to the database one year later, to provide the elusive diagnosis. The case studies exemplify increasing value of the database as clinicians add case information.

“DECIPHER is particularly useful when we look at patients with developmental delay, learning disability, dysmorphic features or congenital abnormalities, where, using genomic array technology, we can assign a diagnosis in 15 per cent of previously undiagnosed cases. This improvement is dependent on a fantastic level of collaboration. More than 2000 patient cases have been contributed to the DECIPHER database since its inception: its diagnostic power strengthens as new cases are added.”

Helen Firth Consultant Clinical Geneticist at Addenbrookes Hospital and lead author on the study

DECIPHER is built upon the Ensembl genome browser. It is the only open-access, web-based interactive database of its type, although data from other databases are available. The report’s authors suggest that while combination of all data in one resource would be ideal, providing access to the data in one genome browser is a realistic and practical method of harnessing the combined power of the datasets.

Sharing data between researchers is increasingly important. As the role of CNVs in human disease is better understood, so resources such as DECIPHER will gain momentum that will drive significant health benefits and improvements to genetic counselling.

More information


This work was supported by the Wellcome Trust.


Collaborating Institution

  • Cambridge University Department of Medical Genetics, Addenbrookes Hospital, Cambridge, UK.
  • The Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.
  • K. U. Leuven, ESAT/SCD, Kasteelpark Arenberg, Leuven-Heverlee, Belgium.


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Selected websites

  • University of Cambridge

    As the University of Cambridge celebrates its eight-hundredth anniversary in 2009, it is looking to the future. Its mission is to contribute to society through the pursuit of education, learning and research at the highest international levels of excellence. It admits the very best and brightest students, regardless of background, and offers one of the UK’s most generous bursary schemes.

    The University of Cambridge’s reputation for excellence is known internationally and reflects the scholastic achievements of its academics and students, as well as the world-class original research carried out by its staff. Some of the most significant scientific breakthroughs occurred at the University, including the splitting of the atom, invention of the jet engine and the discoveries of stem cells, plate tectonics, pulsars and the structure of DNA. From Isaac Newton to Stephen Hawking, the University has nurtured some of history’s greatest minds and has produced more Nobel Prize winners than any other UK institution with over 80 laureates.

  • The Wellcome Trust Sanger Institute

    The Wellcome Trust Sanger Institute, which receives the majority of its funding from the Wellcome Trust, was founded in 1992. The Institute is responsible for the completion of the sequence of approximately one-third of the human genome as well as genomes of model organisms and more than 90 pathogen genomes. In October 2006, new funding was awarded by the Wellcome Trust to exploit the wealth of genome data now available to answer important questions about health and disease.

  • The Wellcome Trust

    The Wellcome Trust is a global charitable foundation dedicated to achieving extraordinary improvements in human and animal health. We support the brightest minds in biomedical research and the medical humanities. Our breadth of support includes public engagement, education and the application of research to improve health. We are independent of both political and commercial interests.