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Platelet Biology Group


The Genetic Aetiology of Rare Diseases

NIHR Bioresource

Key people: Dr Chris PenkettDr Roger JamesSofie Ashford

The National Institute of Health Research has established a BioResource for Rare Diseases. Our group is responsible for the recruitment of patient participants to this resource, for the collation of patient phenotype data and for the sequencing of patient genomes. Genetic epidemiologists and statisticians in the group are analysing the data generated by the Bioresource in order to identify genetic mutations causing diseases as part of the BRIDGE project. 

A rare disease is a condition that has a prevalence of fewer than 5 in 10,000 individuals of the UK population thus affecting approximately 3% of the population.  The aims of the BioResource for Rare Diseases are:

  1. to reduce the delay in ascertaining a genetic diagnosis for inherited and acquired genetic disorders (including rare cancers), where the genotype causing phenotype is known, by developing NGST-based diagnostic tests covering NHS diagnostically-important genes; such projects can include translational projects on e.g. a subset of diagnostic genes,
  2. to determine the genetic basis of Inherited Rare Diseases, including rare cancers for which the causative locus has hitherto not been identified, but which have potential wider relevance for the common diseases that are the focus of Biomedical Research Centres/Units (BRC/BRU)-funded translational and experimental medicine research

Recruitment is via participating BRC/BRU/hospitals with specialist interest in rare diseases.

Currently the main focus of the BRIDGE study fall into the themes: infection and immunity, rare cancers, neuroscience and cardiovascular disease. The active projects are:

Bleeding and Platelet Disorders (BPD) 

Key people: Dr Ernest TurroProfessor Willem Ouwehand

The immediate purpose of this study is to identify the genetic basis of hitherto unresolved bleeding and platelet disorders by exome-sequencing.

Pulmonary Arterial Hypertension (PAH

Key people: Dr Stefan GräfProfessor Willem OuwehandProfessor Nick Morell

The discovery of the range of genetic mutations underlying PAH will provide a more complete picture of the cause of this disease and identify rational targets for new drugs. It will also pave the way towards prevention strategies for this disease and of the prediction of prognosis based on a genetic classification of PAH.

Primary Immune Disorders (PID)

Key people: Dr Hana Lango AllenProfessor Willem Ouwehand

This study focuses on genetic causes of severe immune disorders, also known as Primary ImmunoDeficiencies with the largest category being CVID, but it may also include the “extreme phenotype” of premature and severe autoimmunity.

Specialist Pathology: Evaluating Exomes in Diagnostics (SPEED)

Key people:  Professor Willem OuwehandDr Lucy Raymond

This research project aims to develop more affordable DNA-based tests for the diagnosis of rare diseases for which the gene is known.

Steroid Resistant Nephrotic Syndrome (SRNS)

This study focuses on genetic causes Steroid Resistant Nephrotic Syndrome.

Genetics of haematological traits

Key people: Dr William Astle, Professor Nicole Soranzo, Professor Willem Ouwehand.

Discovering new gene functions through genome wide association studies of blood indices and elucidating the molecular mechanisms by which sequence variation alters these traits.