PhD Studentship: Integrative Analysis of Whole Genomes and Transcriptomes From Multiple Cell Types in Rare Disease Patients

About the GW4 BioMed2 Doctoral Training Partnership

The partnership brings together the Universities of Bath, Bristol, Cardiff (lead) and Exeter to develop the next generation of biomedical researchers. Students will have access to the combined research strengths, training expertise and resources of the four research-intensive universities, with opportunities to participate in interdisciplinary and 'team science'. The DTP already has over 90 studentships over 6 cohorts in its first phase, along with 58 students over 3 cohorts in its second phase.

Project Information

Research Theme: Population Health Sciences

Summary: Comprehensive genetic analysis using whole genome sequencing (WGS) still fails to identify the genetic cause of diseases in about 50% of patients with rare diseases. To increase this yield, the NIHR BioResource for Rare Disorders launched the RNA phenotyping initiative, which combines RNA-sequencing and proteomic data with WGS for 1000 patients with rare diseases. This PhD project will develop new approaches to integrate these data to identify new causes of disease.

Project Description: The use of Whole-Genome Sequencing has dramatically increased the diagnostic yield and shortened the time to diagnosis for individuals affected by rare diseases. However, WGS still fails to identify the underlying genetic cause in about 50% of patients.
This is due to several factors, mainly:

1. lack of statistical power due to small sets of cases with different genetic aetiology,
2. difficulty in predicting the consequences of a number of causal genetic variants, and lastly,
3. challenges with identifying structural variants using current WGS techniques.

To increase the percentage of individuals receiving a diagnosis the NIHR National BioResource for Rare Diseases launched the RNA phenotyping initiative. Here, WGS is supplemented with RNA-sequencing from four highly purified blood cell types and proteomic data from the same cells and plasma.

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