Research led by scientists at Queen Mary University of London is heralding in a new era for genetic sequencing and testing.
In the largest study of its kind to date, published today in Nature Medicine, an international group of researchers led by Queen Mary used new bioinformatics techniques to scan the genetic profiles of 80,000 people to understand the frequency of specific expansions of short repetitive DNA sequences in the general population.
These expansions are the most common cause of inherited neurological conditions, known as repeat expansion disorders (REDs). The study’s results showed that REDs are up to three times more frequent than current estimates, which are based on clinical observation or disease diagnosis. It was also found that their frequency is common between different populations.
Dr Arianna Tucci, Clinical Reader in Genomic Medicine at Queen Mary University of London who led the research, said: “This very important advance may indicate that REDs like Huntington’s disease are nearly three times more common than we think, meaning we’re underdiagnosing these conditions. Alternatively, the presence of certain DNA repeats may not lead to illness in some people. This could herald a major shift in how we think about genetic testing, profiling and counselling.
“These findings were only possible because we are able to study whole genomes from the 100,000 Genomes Project in many individuals at scale. This represents a paradigm shift from traditional studies of small families with a history of a genetic condition to the analysis of large populations of individuals. Our next steps will be to study large cohorts of people that carry these genetic changes, to help us better understand what leads them to develop in certain individuals.”
Dr Sarah Tabrizi, Professor of Clinical Neurology at the UCL Queen Square Institute of Neurology and co-author on the paper, said: “These results are extremely important. These data will force us as a community of researchers, academics and doctors to evaluate whether these DNA repeats address an unmet diagnostic need in rare neurological diseases, meaning the investigation of repeat expansion disorders deserves much more close attention now.”
Examples of RED conditions include Fragile X syndrome, the commonest inherited form of amyotrophic lateral sclerosis and frontotemporal dementia, Huntington’s disease, inherited ataxias (Friedreich ataxia), and RFC1-Cerebellar Ataxia, Neuropathy, Vestibular Areflexia syndrome (CANVAS).
- Ibañez K, Jadhav B, Zanovello M, et al. Increased frequency of repeat expansion mutations across different populations. Preprint. medRxiv. 2024 Jul 8. doi:10.1101/2023.07.03.23292162