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 …

Background With the expanding use of next-gen sequencing (NGS) to diagnose the
thousands of rare Mendelian genetic diseases, it is critical to be able to interpret individual …

Recessive diseases arise when both copies of a gene are impacted by a damaging genetic
variant. When a patient carries two potentially causal variants in a gene, accurate diagnosis …

Whole-exome sequencing (WES) has facilitated the discovery of genetic lesions underlying
monogenic disorders. Incomplete penetrance and variable expressivity suggest a …

The increasing size and complexity of exome/genome sequencing data requires new tools
for clinical geneticists to discover disease-causing variants. Bottlenecks in identifying the …

Large analyses dredge up'peripheral'genetic associations that offer little biological insight,
researchers say. Full Text: Author (s): Ewen Callaway Author Affiliations: Genome-wide …

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 …

A striking finding from recent large-scale sequencing efforts is that the vast majority of
variants in the human genome are rare and found within single populations or lineages …

Whole‐exome sequencing (WES) and whole‐genome sequencing (WGS) studies are
underway to investigate the impact of genetic variants on complex diseases and traits. It is …

Many exome sequencing studies of Mendelian disorders fail to optimally exploit family
information. Classical genetic linkage analysis is an effective method for eliminating a large …