Bioinformatics techniques reveal hidden prevalence of repeat expansion disorders

Research by scientists at Queen Mary University of London heralds a new era in genetic sequencing and testing. In the largest study of its kind to date, published today in Natural medicineAn international group of researchers led by Queen Mary used new bioinformatics techniques to analyze 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 diseases, known as repeat expansion disorders (RED). The study results showed that REDs are up to three times more common than current estimates, based on clinical observation or diagnosis of the disease. It has also been 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 could indicate that REDs like Huntington’s disease are almost three times more common than we think so, which means we are underdiagnosed. these conditions.

“Alternatively, the presence of certain DNA repeats may not lead to disease in some people. This could herald a major shift in the way we think about genetic testing, profiling and counseling.

“These results were only possible because we are able to study entire genomes from the 100,000 Genomes Project in many individuals on a large scale. This represents a paradigm shift from traditional studies of small families with histories of genetic disease towards the analysis of large populations of individuals.

“Our next steps will be to study large cohorts of people carrying these genetic changes, to help us better understand what causes them to develop in certain individuals.”

Dr Sarah Tabrizi, Professor of Clinical Neurology at the UCL Queen Square Institute of Neurology and co-author of the paper, said: “These findings are extremely important. These data will compel us as a community of researchers, academics, and physicians to evaluate whether these DNA repeats serve an unmet diagnostic need in rare neurological diseases, meaning that the investigation of expansion disorders repeated now deserves much more particular attention.