Variant Views

Evidence for 28 Genetic Disorders Discovered by Combining Healthcare and Research Data

By Malorye Branca on March, 5 2021


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Primary reference: Kaplanis, J. et al. Nature, Oct. 14. 2020.

Conditions: Developmental disorders. 

To identify previously undescribed genes associated with developmental disorders, researchers have integrated healthcare (clinical record) and research exome-sequence data from 31,058 parent–offspring trios of individuals with developmental disorders, and developed a simulation-based statistical test to identify gene-specific enrichment of de novo mutations. This study is part of the Deciphering Developmental Disorders project which has spent four years collecting DNA and clinical information from over 12,000 undiagnosed children and adults in the UK with developmental disorders and their parents. 

They identified 285 genes that were significantly associated with developmental disorders, including 28 that had not previously been robustly associated with developmental disorders. Much of the excess of de novo mutations in protein-coding genes remains unaccounted for. They note that: "Modelling suggests that more than 1,000 genes associated with developmental disorders have not yet been described, many of which are likely to be less penetrant than the currently known genes. Research access to clinical diagnostic datasets will be critical for completing the map of genes associated with developmental disorders"

Sequence and variant-level data and phenotypic data for the Deciphering Developmental Disorders study data are available from the European Genome-phenome Archive (EGA; with study ID EGAS00001000775


Additional resource:

The DDD has produced more than 200 publications which are available at its website.


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