Abstract

The majority of children with severe developmental disorders remain without a genetic diagnosis. Families often describe the road to reaching a diagnosis as an ‘odyssey’ lasting years and involving dozens of different medical professionals. The Deciphering Developmental Disorders (DDD) study has collected detailed clinical phenotypes and genome sequence data from 14,000 children with undiagnosed developmental disorders and their parents as an effort to quickly and definitively reach a genetic diagnosis. Using data from the first 4,000 DDD patients, my computational analyses have already generated hypotheses relating to specific variants in individual genomic functional elements. This work will contribute to an improved understanding of the role of the regulatory genome in developmental disorders and provides a scalable model for the interpretation of non-coding elements in rare disease cohorts.