Deciphering Developmental Disorders (DDD)

The Deciphering Developmental Disorders (DDD) study aims to use new genomic technologies to improve the diagnosis of developmental disorders in children. It is a collaboration between the NHS clinical genetics services, the Wellcome Trust Sanger Institute and families across the UK.

[Deciphering Developmental Disorders]


Thousands of babies are born each year in the UK with errors in their genetic makeup that affect their development. Diagnosis of developmental disorders is currently restricted to a small minority of children and requires the clinician to recognise the appearance of the child and the pattern of symptoms, supplemented by the use of microscopes to identify large rearrangements of the genetic material in chromosomes. Research shows that the latest molecular testing methods identify previously undetectable changes in chromosomes allowing new diagnoses to be made. However, clinical use is hampered by the limited availability and inconsistent application of these technologies, and by lack of basic knowledge to link genetic changes directly to symptoms. The consequence is that clinical diagnoses remain impossible except for a small number of children.

The DDD study

The study is led jointly by Nigel Carter, Matthew Hurles and Jeffrey Barrett at the Wellcome Trust Sanger Institute supported by large team of dedicated scientists; Helen Firth at Addenbrooke's Hospital in Cambridge, David Fitzpatrick at the Human Genetics Unit in Edinburgh and Mike Parker at the Ethox Centre in Oxford.

The results of the DDD study will provide a unique, online catalogue of genetic changes linked to clinical features that will enable clinicians to diagnose developmental disorders. Furthermore, the study will enable the design of more efficient and cheaper diagnostic assays for relevant genetic testing to be offered to all such patients in the UK and so transform clinical practice for children with developmental disorders.

Over time, the work will also improve understanding of how genetic changes cause developmental disorders and why the severity of the disease varies in individuals.

The Sanger Institute will contribute to the DDD study by performing genetic analysis of DNA samples from patients with developmental disorders, and their parents, recruited into the study through the Regional Genetics Services. Using microarray technology and the latest DNA sequencing methods, research teams will probe genetic information to identify mutations (DNA errors or rearrangements) and establish if these mutations play a role in the developmental disorders observed in patients.

The DDD initiative grew out of the groundbreaking DECIPHER database, a global partnership of clinical genetics centres set up in 2004, which allows researchers and clinicians to share clinical and genomic data from patients worldwide. The DDD study aims to transform the power of DECIPHER as a diagnostic tool for use by clinicians.

Tools for clinicians and researchers

An important aspect of the study will be the development of information technology to support clinicians in their diagnosis and management of children with developmental disorders. The study team hopes to deliver cost-effective and accurate tools for doctors to analyse the cause of developmental disorders within the next three to five years. By developing a comprehensive knowledge base and computer tools to allow researchers to interpret genetic findings, DDD will help to unlock the complex role of chromosomal abnormalities in disease. Using this knowledge, DDD will enable the development of new pre- and postnatal diagnostic tests that could eventually be rolled out for all patients with developmental disorders in the UK.

Empirical research, ethical analysis

Ethics research is a core part of the DDD study, and aims to pave the way for an informed public debate about the ethical and social implications of the use of whole genome sequencing in health care and its appropriate control. Alongside its core biomedical research, the DDD team will carry out empirical social science and ethics research on the views of health professionals, NHS laboratory staff and families about the implications of DDD methods in the clinical setting. Based on these investigations, the team will develop new models for good practice and explore particular practical ethical issues around producing data and sharing results with patients in the context of uncertainty about their implications. This research will also explore broader questions around the ethics of whole genome sequencing in the clinical setting.

Data access

As well as improving patient care, the DDD team will empower researchers in the field by making the data generated securely available to other research teams around the world. By assembling a solid resource of high-quality, high-resolution and consistent genomic data, the leaders of the DDD study hope to extend the reach of DECIPHER across a broader spectrum of disorders than is currently possible.

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