Rare, evolutionarily recent variants have larger effect sizes and are more likely to decrease fitness, providing evidence that quantitative traits in yeast have evolved under purifying selection.

Rare highly damaging mutations that are present in most human genomes decrease lifespan and are associated with an earlier onset of chronic diseases.

Studying the impact of natural variation on a key immune gene highlights how focusing on a single wild-type sequence overlooks that rare variants cause the most disease.

Disruption of epoxide hydrolysis inducing oxidative stress and cellular senescence is a novel mechanism responsible for lipoatrophic monogenic diabetes.

Epistatic interactions of rare loss of function mutations in SMAD6 and a common variant modifier near BMP2 are the most common cause of midline craniosynostosis in humans.

Evidence is mounting that rare loss-of-function variants in the TLR7 gene predispose men with no medical history to severe forms of COVID-19.

Genetic sequencing has led to the increased diagnoses of rare diseases, strategies such as repurposing drugs and global metabolomics offer promise and bring hope to afflicted families.

Rare SARM1 alleles encoding SARM1 variants that have constitutively high NADase activity and sensitise cultured neurons to mild stress are risk alleles for ALS and other, related motor disorders.

A novel statistical framework and approach using sibling phenotype pairs allows inference of genetic architecture in the tails of complex traits to be made without genetic data.

Although cellular organelles show a functional deterioration in aging, genetic loci associated with common age-associated disease instead nominate nuclear transcription factors across several age-related diseases.