Despite three decades of successful, predominantly phenotype-driven discovery of the
genetic causes of monogenic disorders, up to half of children with severe developmental …

The genomes of individuals with severe, undiagnosed developmental disorders are
enriched in damaging de novo mutations (DNMs) in developmentally important genes. Here …

De novo mutations in protein-coding genes are a well-established cause of developmental
disorders. However, genes known to be associated with developmental disorders account …

We previously estimated that 42% of patients with severe developmental disorders carry
pathogenic de novo mutations in coding sequences. The role of de novo mutations in …

Discovery of most autosomal recessive disease-associated genes has involved analysis of
large, often consanguineous multiplex families or small cohorts of unrelated individuals with …

There are thousands of rare human disorders that are caused by single deleterious, protein-
coding genetic variants. However, patients with the same genetic defect can have different …

Approximately one-third of all mammalian genes are essential for life. Phenotypes resulting
from knockouts of these genes in mice have provided tremendous insight into gene function …

Recent research has uncovered an important role for de novo variation in
neurodevelopmental disorders. Using aggregated data from 9,246 families with autism …

Human genetics is now at a critical juncture. The molecular methods used successfully to
identify the genes underlying rare mendelian syndromes are failing to find the numerous …

New mutations have long been known to cause genetic disease, but their true contribution to
the disease burden can only now be determined using family-based whole-genome or …