ICG is part of the gnomAD consortium

The Genome Aggregation Database (gnomAD), is a coalition of investigators seeking to aggregate and harmonize exome and genome sequencing data from a variety of large-scale sequencing projects and to make summary data available for the broader scientific community. 

In its first release, it was known as the Exome Aggregation Consortium (ExAC).
The data set provided on the gnomAD website spans now 125,748 exomes and 15,708 genomes from unrelated individuals sequenced as part of various disease-specific and population genetic studies, totaling 141,456 individuals.

The ICG is part of this amazing resource by contributing the North German MI Study and will be listed under the umbrella: Genome Aggregation Database Consortium.

Currently, the main investigators are submitting several papers as preprints to biorxiv, while in parallel the manuscripts are sent to Nature or other high-impact journals.

Over the next weeks, I will update the list of submitted papers with a very short summary of the main results. Stay tuned! 

Evaluating potential drug targets through human loss-of-function genetic variation by Eric Vallabh Minikel et al.
Main results
  • Human genetics is more and more important for drug development
  • Large-scale DNA sequencing studies have created a catalogue of naturally occurring genetic variants predicted to cause LOF in human genes 
  • Many drug targets are under natural selection with pLoF variants almost completely depleted from the population
  • Thus, metrics of gene essentiality should not be used to eliminate genes from consideration as potential targets
  • The identification of individual humans harboring "knockouts", followed by individual recall and deep phenotyping, is highly valuable to study gene function
  • In most genes, pLoF alleles are sufficiently rare that ascertainment will be largely limited to heterozygous individuals in outbred populations
  • Sampling of diverse bottlenecked populations and consanguineous individuals will aid in the identification of total "knockouts"
  • Careful filtering and curation of pLoF variants in a gene of interest is necessary to identify true LoF individuals for follow-up