Understanding how chromatin is folded in the nucleus is fundamental to understanding its
function. Although 3D genome organization has been historically difficult to study owing to a …

A gene can be defined as essential when loss of its function compromises viability of the
individual (for example, embryonic lethality) or results in profound loss of fitness. At the …

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

Detailed knowledge of how diversity in the sequence of the human genome affects
phenotypic diversity depends on a comprehensive and reliable characterization of both …

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

Background Splicing of genomic exons into mRNAs is a critical prerequisite for the accurate
synthesis of human proteins. Genetic variants impacting splicing underlie a substantial …

Abstract Combined Annotation-Dependent Depletion (CADD) is a widely used measure of
variant deleteriousness that can effectively prioritize causal variants in genetic analyses …

INTRODUCTION Our understanding of the pathophysiology of psychiatric disorders,
including autism spectrum disorder (ASD), schizophrenia (SCZ), and bipolar disorder (BD) …

Metabolic diseases are the most common and rapidly growing health issues worldwide. The
massive population-based human genetics is crucial for the precise prevention and …

Complex traits and common diseases are extremely polygenic, their heritability spread
across thousands of loci. One possible explanation is that thousands of genes and loci have …