A tremendous amount of effort has gone into using human genomic studies to find sleep genes. Some studies have hundreds of thousands of individuals. But validation and testing in animal models are critical to understanding its function.

A new study has reached that point here. Using human genomics, a team of scientists from Texas A&M University, the Perelman School of Medicine at the University of Pennsylvania, and the Children’s Hospital of Philadelphia (CHOP) have identified a novel genetic pathway involved in regulating sleep of fruit flies to humans.

The most exciting thing about the study: Scientists developed a pipeline that started not with a model organism, but with real human genomics data.

Texas A&M geneticist and evolutionary biologist Alex Keene said: “There is a plethora of human genome-wide association studies (GWAS) that identify genetic variants associated with sleep in humans. However, validating it was a huge challenge. Our team used a genomics approach called variant-to-gene mapping to predict the genes affected by each genetic variant. We then screened the effect of these genes in fruit flies.”

“Our studies found that mutations in the Pig-Q gene, required for the biosynthesis of a modifier of protein function, increased sleep. We then tested this in a vertebrate model, the zebrafish, and found a similar effect. Therefore, Pig-Q is associated with sleep regulation in humans, flies and zebrafish.”

“The team’s next step is to study the role of a common protein modification, GPI anchor biosynthesis, on sleep regulation. In addition, he notes that the human-to-fruitfly-to-zebrafish pipeline the team has developed will allow them to functionally assess sleep not only genes, but also other traits commonly studied using human GWAS, including neurodegeneration, aging and memory.

Penn’s Philip Gehrman said: “Understanding how genes regulate sleep and the role of this pathway in sleep regulation may help unlock future findings on sleep and sleep disorders, such as insomnia. Going forward, we will continue to use and study this system to identify more genes that regulate sleep.” , which could point to new treatments for sleep disorders.”

Magazine reference:

  1. Justin Palermo et al. Variant-to-gene mapping followed by cross-species genetic screening identifies GPI anchor biosynthesis as a sleep regulator. Scientific progress. Paper link