Danish Saleheen

The mutational constraint spectrum quantified from variation in 141,456 humans

Nature · 2020 · 9986 citations

. Here we describe the aggregation of 125,748 exomes and 15,708 genomes from human sequencing studies into the Genome Aggregation Database (gnomAD). We identify 443,769 high-confidence predicted loss-of-function variants in this cohort after filtering for artefacts caused by sequencing and annotation errors. Using an improved model of human mutation rates, we classify human protein-coding genes along a spectrum that represents tolerance to inactivation, validate this classification using data fr…

Sequencing of 53,831 diverse genomes from the NHLBI TOPMed Program

Nature · 2021 · 2261 citations

. In the first 53,831 TOPMed samples, we detected more than 400 million single-nucleotide and insertion or deletion variants after alignment with the reference genome. Additional previously undescribed variants were detected through assembly of unmapped reads and customized analysis in highly variable loci. Among the more than 400 million detected variants, 97% have frequencies of less than 1% and 46% are singletons that are present in only one individual (53% among unrelated individuals). These…

A genomic mutational constraint map using variation in 76,156 human genomes

Nature · 2023 · 1281 citations

A structural variation reference for medical and population genetics

Nature · 2020 · 1149 citations

and will have broad utility in population genetics, disease-association studies, and diagnostic screening.

The power of genetic diversity in genome-wide association studies of lipids

Nature · 2021 · 1032 citations