More than a hundred genes have been identified that, when disrupted, impart large risk for
autism spectrum disorder (ASD). Current knowledge about the encoded proteins—although …

The majority of rare diseases affect children, most of whom have an underlying genetic
cause for their condition. However, making a molecular diagnosis with current technologies …

The depletion of disruptive variation caused by purifying natural selection (constraint) has
been widely used to investigate protein-coding genes underlying human disorders,,–, but …

Rare coding variation has historically provided the most direct connections between gene
function and disease pathogenesis. By meta-analysing the whole exomes of 24,248 …

The depletion of disruptive variation caused by purifying natural selection (constraint) has
been widely used to investigate protein-coding genes underlying human disorders, but …

To capture the full spectrum of genetic risk for autism, we performed a two-stage analysis of
rare de novo and inherited coding variants in 42,607 autism cases, including 35,130 new …

Personalized genome sequencing has revealed millions of genetic differences between
individuals, but our understanding of their clinical relevance remains largely incomplete. To …

Genetic variants that inactivate protein-coding genes are a powerful source of information
about the phenotypic consequences of gene disruption: genes that are crucial for the …

Structural variants (SVs) rearrange large segments of DNA and can have profound
consequences in evolution and human disease,. As national biobanks, disease-association …

Autism spectrum disorder (ASD) is a highly heritable and heterogeneous group of
neurodevelopmental phenotypes diagnosed in more than 1% of children. Common genetic …