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The work was done in collaboration with colleagues from KU Leuven, Belgium; the University of Tokyo; the University of Maryland; Imperial College London and others around the world.

A better understanding of the functions of the genes involved in these and other disorders could pave the way for the development of treatments. The findings are published today (March 16) in the online edition of Natural medicine.

Rare diseases affect approximately 1 in 20 people, but only a minority of patients receive a genetic diagnosis. Less than half of the 10,000 registered rare diseases have a known genetic cause. Genome sequencing of large cohorts of patients with rare diseases provides a way to discover as yet unknown genetic causes. However, large genetic data sets are difficult to work with, which slows down research significantly, the researchers said.

Ernest Turro, associate professor of genetics and genomic sciences at Icahn Mount Sinai and lead author of the study, said: “While rare diseases are individually rare, collectively they are quite common. It is important for our understanding of human biology and for development Diagnostic and therapeutic found the remaining causes.

“Many people with rare diseases struggle for many years to obtain a genetic diagnosis. By developing and applying statistical methods and computational approaches to find new causes of rare diseases, we hope to expand knowledge of the underlying causes of these diseases, speed up the time to diagnosis of patients and pave the way for treatment development.

The researchers studied a collection of 269 rare disease classes using data from 77,539 participants in the 100,000 Genomes Project, one of the largest data sets of rare disease patients with phenotyping and whole genome sequencing. The researchers identified 260 associations between genes and rare disease classes, including 19 associations previously absent from the literature. Through an international academic collaboration, the authors validated the three most plausible novel associations by identifying additional cases in other countries and using experimental and bioinformatics approaches.

Daniel Greene, a postdoctoral fellow at Icahn Mount Sinai and lead author of the study, added: “We hope that our computational framework will help accelerate the discovery of the remaining unknown etiologies of rare diseases across the board. For now, we hope that a genetic diagnosis it will be feasible for certain families with previously unexplained primary lymphedema, thoracic aortic aneurysm, and deafness.

“We also plan to apply our methods in novel ways and on other data sets, with the goal of continuing to unravel the genetic causes of rare diseases.”

Andrew Mumford, Professor of Hematology at the University of Bristol, Research Director of the NHS South West Genomic Medicine Service (GMS) Alliance and co-principal investigator of the study in the UK, explained: “The genetic discoveries identified in our study are the product of a truly international collaboration of experts in computation from Mount Sinai in New York and functional genomics from the University of Leuven.

“I am delighted to have contributed by providing the clinical genomics expertise required to integrate statistical and functional genomic data to produce findings that are relevant to the NHS Genomic Medicine Service.

“This research is an important result of the NHS 100,000 Genomes Project, which was made possible by the large-scale involvement of doctors within the NHS, including significant contributions from Bristol’s two hospital trusts: the North Bristol NHS Trust (NBT ) and the University Hospitals of Bristol and Weston. NHS Foundation Trust (UHBW)”.

Paper

‘Genetic association analysis of 77,539 genomes reveals etiologies of rare diseases’ by Ernest Turro, Daniel Greene, Andrew Mumford et al. in Natural medicine