Draft:Deciphering Developmental Disorders project

Deciphering Developmental Disorders project

The DDD (Deciphering Developmental Disorders) study is a large-scale genetic research project focused on understanding the causes of developmental disorders in children. It was launched in 2010 in the UK and led by the Wellcome Sanger Institute in collaboration with the NHS.

Key Points of the Study:

Objective: To identify genetic variants responsible for severe developmental disorders in children. Participants: Over 13,000 families with children affected by unexplained developmental conditions (1). Methods: The DDD study used arrayCGH, whole exome sequencing (WES) and later whole genome sequencing (WGS) to analyse DNA and identify mutations (2). Findings:

• Discovered new genetic causes for developmental disorders.
• Showed that many of these conditions result from de novo (new) mutations, meaning they are not inherited from parents.
• Identified specific genes linked to various conditions, improving diagnosis and potential treatments.

Impact:

• Helped clinicians provide better genetic diagnoses for families.
• Contributed to the 100,000 Genomes Project and other genetic research initiatives.
• Enhanced understanding of rare diseases, influencing healthcare and genetic counselling.

The DDD study was led by a team of researchers from the Wellcome Sanger Institute and the UK National Health Service (NHS). Some of the key researchers involved include:

1. Dr. Matthew Hurles (Academic Lead)

• Role: Principal Investigator of the DDD study.
• Affiliation: Wellcome Sanger Institute.
• Key Contributions:
  • Led the study’s genetic analysis efforts.
  • Pioneered research on de novo mutations in developmental disorders.
  • Played a major role in integrating whole exome sequencing (WES) into clinical diagnostics.

2. Professor Helen Firth (Clinical Lead)

• Role: Consultant Clinical Geneticist & Lead Clinician for the DDD Study
• Affiliation:
  • Cambridge University Hospitals (Addenbrooke’s Hospital)
  • Wellcome Sanger Institute
• Key Contributions:
  • Founder of DECIPHER – a pioneering database that helps clinicians and researchers share genetic variants linked to developmental disorders.
  • Played a major role in translating genetic discoveries into clinical practice, ensuring that findings from the DDD study were useful for real-world diagnosis and patient care.
  • Led efforts to create a standardized system for classifying genetic variants, improving the accuracy of diagnoses.
  • Worked extensively in rare disease genetics, helping identify novel genetic conditions.

3. Professor Caroline Wright

• Role: Expert in Genomic Medicine and former project manager of the DDD Study.
• Affiliation: University of Exeter (previously at the Wellcome Sanger Institute).
• Key Contributions:
  • Worked on translating genomic findings into clinical practice.
  • Helped develop guidelines for genetic testing and counseling based on DDD findings.

4. Dr. Michael Parker

• Role: Ethicist specializing in genomic research.
• Affiliation: University of Oxford.
• Key Contributions:
  • Led the ethical framework for genetic testing, ensuring families receive results responsibly.
  • Studied the implications of returning uncertain genetic findings to families.

5. Dr. David FitzPatrick

• Role: Clinical Geneticist.
• Affiliation: MRC Human Genetics Unit, University of Edinburgh.
• Key Contributions:
  • Identified new genetic syndromes through the DDD study.
  • Worked on clinical diagnosis and genetic counseling for families.

Collaborating Institutions:

• Wellcome Sanger Institute (UK) – Led the genomic sequencing efforts.
• NHS Regional Genetics Services – Provided patient data and clinical insights.
• Genomics England – Incorporated DDD findings into the broader 100,000 Genomes Project.

References

1. https://www.nejm.org/doi/10.1056/NEJMoa2209046

2. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(14)61705-0/fulltext