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

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

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 …

Rare, atypical, and undiagnosed autosomal‐recessive disorders frequently occur in the
offspring of consanguineous couples. Current routine diagnostic genetic tests fail to …

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

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 …

Standard techniques from genetic epidemiology are ill-suited to formally assess the
significance of variants identified from a single case. We developed a statistical inference …

The unmasking of recessive mutations by virtue of biparental inheritance of the same
ancestral haplotype on which they reside (autozygosity) has provided human geneticists …

Genotypes causing pregnancy loss and perinatal mortality are depleted among living
individuals and are therefore difficult to find. To explore genetic causes of recessive lethality …

Exome sequencing of parent-offspring trios is a popular strategy for identifying causative
genetic variants in children with rare diseases. This method owes its strength to the …