Cotton Seed

TL;DR: A catalogue of predicted loss-of-function variants in 125,748 whole-exome and 15,708 whole-genome sequencing datasets from the Genome Aggregation Database (gnomAD) reveals the spectrum of mutational constraints that affect these human protein-coding genes.

TL;DR: Using an improved human mutation rate model, human protein-coding genes are classified along a spectrum representing tolerance to inactivation, validate this classification using data from model organisms and engineered human cells, and show that it can be used to improve gene discovery power for both common and rare diseases.

TL;DR: Large-scale deep-coverage whole-genome sequencing is now feasible and offers potential advantages for locus discovery and the incremental value of WGS for discovery is limited but WGS permits simultaneous assessment of monogenic and polygenic models to severe hypercholesterolemia.

TL;DR: A novel variant annotation metric that quantifies the level of expression of genetic variants across tissues is validated in the Genome Aggregation Database (gnomAD) and is shown to improve rare variant interpretation.

TL;DR: It is demonstrated that this newly discovered mode of AAV binding and transduction can occur independently of other known AAV receptors, and inform ongoing efforts to develop next-generation AAV vehicles for human CNS gene therapy.