The Rare Diseases RNA Phenotyping project is a follow-on from our study that sequenced the whole genome of 8,000 participants. This was conducted by the NIHR BioResource Rare Diseases consortium, who were looking to find more information about the genetic causes behind rare diseases. This work resulted in 20% of participants receiving a diagnosis.
This latest study aims to increase this diagnosis rate further and provide a greater understanding of how and why rare disease may arise. As well as further investigating the DNA of participants, the project also focuses on understanding more about their RNA and proteins. RNA is the molecule in our cells that helps to translate sections of our DNA into proteins. This process is required for our cells to work correctly. Certain changes within DNA or RNA can stop proteins from functioning correctly, which can lead to someone being affected by a rare disease. By comparing how RNA functions in people with rare diseases to those without, we hope to understand more about what may cause a rare disease.
How the study works
Participants in the project are asked to donate a 50 ml blood sample. This is transported to our laboratory where three types of white blood cell - neutrophils, monocytes and T Helper cells – are isolated alongside platelets, which are the cells that help our blood to clot. From these cells we extract RNA; this is then sequenced to understand the underlying RNA code. To support the RNA analysis, we will sequence the participants’ DNA and analyse the structure and quantity of the proteins that are potentially contributing to the rare disease.
Alongside collecting a blood sample, we also collect clinical information. This will help to build a strong overall picture of a person’s condition and symptoms. To support any findings, we also recruit participants without a disease (known as “controls”) so that we can compare the results with data from those with rare disease. This information may help us to identify any changes to the DNA, RNA and proteins that might be contributing to a participant’s rare disease.
The project is investigating 17 different rare diseases, including immunological conditions, kidney disorders, inherited neurological disorders, genetic eye conditions, mitochondrial disease, and blood disorders.
Professor Sinisa Savic, Professor of Clinical Immunology at the University of Leeds and the Rare Diseases BioResource co-lead said:
“Reaching 1,000 participants in the Rare Diseases RNA study is a remarkable milestone and a testament to the commitment of our patients, clinical teams and research partners. This level of engagement gives us an unprecedented opportunity to deepen our understanding of rare conditions and accelerate the development of earlier, more precise diagnoses. We are incredibly grateful to everyone who contributed to this achievement, which brings us a significant step closer to transforming care for people living with rare diseases.”
Thanks to the contributions of our participants, clinical teams and researchers, we hope that our investigations will build a more complete picture of what is happening in someone’s body when they have a rare disease. This information will help doctors and scientists to understand more about what causes rare disease with the hope of improving diagnosis and treatment options in the future.
Now we have reached our recruitment goal, the next step is to finish producing the data and begin the analysis. Once analysis has been completed, the data will be made available for additional researchers to apply for access so they can conduct approved studies into the causes of rare disease.
A very heartfelt thank you to everyone who has participated so far in this study.
Find out more about the Rare Diseases RNA phenotyping project
If you are a researcher interested in working with the NIHR BioResource to support your study, please get in touch.
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