UCL Great Ormond Street Institute of Child Health


Great Ormond Street Institute of Child Health




The HIGH-5 Programme


Major investment from the National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London is supporting the development of a new high definition, in-depth phenotyping at GOSH (HIGH-5) programme.

HIGH-5 aims to address a major challenge in the understanding of rare diseases: how high penetrance genetic variants interact with genomic modifier alleles, non-genetic determinants and environmental factors to influence disease pathology.

The primary aim of this research is to analyse and integrate genomic, clinical and molecular phenotype information from patients with rare childhood diseases. This will allow the identification of clinical biomarkers that will inform likely disease severity and progression, risk of developing specific clinical complications, and/or stratify patients for appropriate or novel therapies.


Towards personalised medicine for rare diseases

  • Every individual is different as a result of our unique genetic make-up and exposure to differing environments.
  • Patients affected by rare diseases with similar or identical primary genetic defects can markedly vary in their expression of clinical phenotypes, even in patients within the same family.
  • Access to multiple technological advances now offers an exceptional opportunity for in depth phenotyping of disease at the molecular level to evaluate genetic variants in conjunction with detectable variation in RNA, protein, metabolites and epigenetic factors in patient derived tissue.

HIGH-5 will look beyond the identification of disease causing variants by integrating clinical and multi-omics datasets to obtain a more complete understanding of childhood diseases. 

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Using state-of-the-art resources, this approach represents a multidisciplinary strategy to investigate the phenotypic variability that is a feature of many rare diseases. HIGH-5 serves as an important archetypal study for future studies on other rare and complex conditions researched at GOSH and UCL ICH.