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Rare disease diagnosis by 100,000 genomes pilot

As our readers well know, rare diseases are a global health-care challenge, with almost 10,000 conditions that affect 6% of the Western population. There is a genetic component to more than 80% of rare diseases, and these conditions can be disabling and costly to treat. With the development of next-generation sequencing in recent years, the diagnosis rates of rare diseases have improved greatly. 

In 2013, the UK government launched the 100,000 genome project to address the lack of diagnosis by applying whole-genome sequencing to study rare diseases, cancers, and infections in a national healthcare setting. A team of researchers from the 100,000 Genomes Project Pilot conducted a pilot study that enrolled families and undertook detailed clinical phenotyping of the proband to evaluate the effect of the whole genome sequencing approach on a genetic diagnosis of rare conditions by the National Health Service (NHS) in the UK. The authors performed various genetic testing on samples obtained from the participants. 

There were a total of 4660 participants in this study (2183 probands and 2477 family members), of which 161 rare diseases were present, neurologic conditions, ophthalmologic conditions, and tumor syndromes appeared most common. There was a wide variation in the numbers of affected and unaffected individuals within each family. The authors aimed to recruit family trios (parents and proband) or larger family structures to facilitate more effective variant prioritization. In this study published in the New England Journal of Medicine, a genetic diagnosis was made in 25% of the probands, and the genotypes were deposited in the ClinVar repository.