RNA-Sequencing
Enhancing genomic diagnostic testing using RNA-Sequencing
There are certain types of genetic changes that are difficult to detect with standard DNA sequencing alone. This means that in some people with a dominant or recessive genetic disorder (caused by a mistake in one or both copies of a gene), we may be unable to confirm the cause of the condition.
Genetic testing sometimes uncovers changes in genes that haven’t been seen before: variants of unknown significance (VUS). When we see a VUS, we need additional information to try and figure out whether this is just part of the normal genetic variation seen in the population or potentially the cause of someone’s medical problems.
Using other technologies can help us detect changes not seen on DNA sequencing and can sometimes clarify whether a VUS is medically important or not.
Project Overview
This project was set up to address some of the limitations associated with standard DNA sequencing.
DNA is how we store genetic information. However, to use a gene, the DNA is first copied into a molecule called RNA. We currently don’t look at RNA when carrying out genetic testing for most conditions. However, looking at RNA can give us information that DNA testing cannot. For example:
- Some changes in DNA that are not detected on routine testing can prevent a gene being copied into RNA – as if the gene has been switched off.
- After being copied into RNA, parts of the DNA code that are not needed are removed through a process called splicing. An estimated 1 in 10 VUS are thought to affect splicing.
The aim of this project is to evaluate whether RNA sequencing (RNA-Seq) can improve diagnosis of genetic conditions and should be used as a standard part of testing in the NHS.
Progress to Date and Next Steps
174 individuals with a range of genetic conditions from the NEY and across the UK have been included in the study, and sequencing has been performed using RNA extracted from blood and fibroblasts (cells grown following skin biopsy).
All of the samples collected have now been processed. Our analysis and reporting team, comprising clinical scientists and experts in bioinformatics, are currently analysing the data and will begin reporting in due course to identify any significant findings not detected on DNA sequencing.
Contact us to learn more.
Our project team are:
Sponsor: Michael Wright, Medical Director, NEY GMS
Lead: Brian Wilson, Consultant in Clinical Genetics, Newcastle upon Tyne Hospitals NHS Trust