Scientists are making progress in decoding the genetics of insomnia
summary: Researchers identify the role the Pig-Q gene plays in regulating sleep. Pig-Q gene mutations increase sleep.
Source: Texas A&M
A research effort involving researchers from Texas A&M University, the Perelman School of Medicine at the University of Pennsylvania, and the Children’s Hospital of Philadelphia (CHOP) has used human genomics to identify a new genetic pathway involved in the regulation of sleep from fruit flies to humans — a novel insight that could pave the way for new treatments. For insomnia and other sleep-related disorders.
Texas A&M geneticist and evolutionary biologist Alex Kane collaborated with Alan Buck of Pennsylvania and Philip German and Struan Grant of CHOP on the groundbreaking research, which is published in Science advances.
“There have been tremendous efforts to use human genome studies to find sleep genes,” Kane said.
Some studies have hundreds of thousands of individuals. But validation and testing in animal models is critical to understanding function. We achieved this here, in large part because we each bring a different area of expertise that allowed for the ultimate efficacy of this collaboration.”
The most exciting thing about the team’s work, Kane says, is that they’ve developed a pipeline that starts not with a model organism, but with actual human genome data.
“There is an abundance of human genome-wide association studies (GWAS) that identify genetic variants associated with sleep in humans,” Kane said.
However, validating it was an enormous challenge. Our team used a genomics approach called gene variant mapping to predict which genes are affected by each genetic variant. We then examined the effect of these genes in fruit flies.
Our studies found that mutations in the Pig-Q gene, which is required for the biosynthesis of the modulator of protein function, increase sleep. We then tested this in a vertebrate model, the zebrafish, and found a similar effect. Therefore, in humans, flies and zebrafish, Pig-Q is associated with sleep regulation.”
The next step for the team, Kane says, is to study the role of a common protein modification, GPI anchor biosynthesis, in sleep regulation. In addition, he noted, the team’s human-to-fruit fly-to-zebrafish transition pipeline would allow them to functionally assess not only sleep genes but also other traits commonly studied using human GWAS, including neurodegeneration, aging, and memory. .
said Germain, associate professor of clinical psychology in psychiatry at the university of penn and a clinical psychologist at the penn chronobiology and sleep institute.
“Going forward, we will continue to use and study this system to identify more genes that regulate sleep, which could point in the direction of new treatments for sleep disorders.”
Kane’s research in his laboratory of the Circadian Research Center lies at the intersection of evolution and neuroscience, with a primary focus on understanding neural mechanisms and the evolutionary underpinnings of sleep, memory formation, and other behavioral functions in model flies and fish.
Specifically, he studies fruit flies (Drosophila melanogaster) and Mexican cavefish that have lost their sight and ability to sleep with the goal of determining the genetic basis of behavioral choices that lead to human diseases, including obesity, diabetes, and heart disease.
About this genetics and insomnia news
author: Shanna K. Hutchins
Source: Texas A&M
Contact: Shana K. Hutchins – Texas A&M
picture: The image is in the public domain
Original search: open access.
“Variant mapping to a gene followed by cross-species genetic screening identifies anchor GPI biosynthesis as a novel regulator of sleep.By Justin Palermo, et al. Science advances
Variant mapping to a gene followed by cross-species genetic screening identifies anchor GPI biosynthesis as a novel regulator of sleep.
Genome-wide association studies (GWAS) in humans have identified loci closely associated with several diseases or genetic traits, yet little is known about the functional roles of underlying causal variants in regulating sleep duration or quality.
We applied the ATAC-seq/promoter-focused Capture C strategy in human iPSC-derived neuronal progenitors to implement a ‘variant-to-gene’ mapping campaign that identified 88 sleep candidate genes associated with relevant GWAS signals.
To functionally verify the role of effector genes involved in sleep regulation, we performed a neuron-specific RNA interference screen in Drosophila, Drosophila melanogaster, followed by zebrafish validation. This approach identified a number of genes that regulate sleep including a critical role in glycosylphosphatidylinositol (GPI) biosynthesis.
These results provide the first somatic-to-genetic variable mapping of human sleep genes followed by organism-based prioritization, revealing a conserved role for GPI-anchor biosynthesis in sleep regulation.