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 …

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

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 …

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

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

Background Human genome sequencing has transformed our understanding of genomic
variation and its relevance to health and disease, and is now starting to enter clinical …

A major goal in human genetics is to use natural variation to understand the phenotypic
consequences of altering each protein-coding gene in the genome. Here we used exome …

Spontaneously arising (de novo) mutations have an important role in medical genetics. For
diseases with extensive locus heterogeneity, such as autism spectrum disorders (ASDs), the …

Large-scale reference data sets of human genetic variation are critical for the medical and
functional interpretation of DNA sequence changes. Here we describe the aggregation and …

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