Thousands of genes influence most diseases
In a provocative new perspective piece, Stanford researchers say that disease genes are spread uniformly across the genome, not clustered in specific molecular pathways, as has been thought.
A core assumption in the study of disease-causing genes has been that they are clustered in molecular pathways directly connected to the disease. But work by a group of researchers at the Stanford University School of Medicine suggests otherwise.
The gene activity of cells is so broadly networked that virtually any gene can influence disease, the researchers found. As a result, most of the heritability of diseases is due not to a handful of core genes, but to tiny contributions from vast numbers of peripheral genes that function outside disease pathways.
Any given trait, it seems, is not controlled by a small set of genes. Instead, nearly every gene in the genome influences everything about us. The effects may be tiny, but they add up.
The work is described in a paper published June 15 in Cell. Jonathan Pritchard, PhD, professor of genetics and of biology, is the senior author. Graduate student Evan Boyle and postdoctoral scholar Yang Li, PhD, share lead authorship.
The researchers call their provocative new understanding of disease genes an “omnigenic model” to indicate that almost any gene can influence diseases and other complex traits. In any cell, there might be 50 to 100 core genes with direct effects on a given trait, as well as easily another 10,000 peripheral genes that are expressed in the same cell with indirect effects on that trait, said Pritchard, who is also a Howard Hughes Medical Institute investigator.
Each of the peripheral genes has a small effect on the trait. But because those thousands of genes outnumber the core genes by orders of magnitude, most of the genetic variation related to diseases and other traits comes from the thousands of peripheral genes. So, ironically, the genes whose impact on disease is most indirect and small end up being responsible for most of the inheritance patterns of the disease.
“This is a compelling paper that presents a plausible and fascinating model to explain a number of confusing observations from genomewide studies of disease,” said Joe Pickrell, PhD, an investigator at the New York Genome Center, who was not involved in the work.
From a polygenic to omnigenic model
Until recently, said Pritchard, he thought of genetically complex traits as conforming to a polygenic model, in which each gene has a direct effect on a trait, whether that trait is something like height or a disease, such as autism.
The Latest on: Disease genes
Study shows DNA methylation related to liver disease among obese patients
on July 18, 2018 at 2:14 pm
a TGen Professor and head of the institute's Diabetes and Fibrotic Disease Unit. Importantly, the study zeroed in on four genes—AQP1, FGFR2, RBP5 and MGMT—that not only were methylated in this study, ... […]
Fetal gene therapy prevents fatal neurodegenerative disease
on July 17, 2018 at 10:22 pm
A fatal neurodegenerative condition known as Gaucher disease can be prevented in mice following fetal gene therapy, finds a new study led by UCL, the KK Women’s and Children’s Hospital and National Un... […]
New platform poised to be next generation of genetic medicines
on July 17, 2018 at 3:54 pm
... have discovered a gene-editing technology that could efficiently and accurately correct the genetic defects that underlie certain diseases, positioning the new tool as the basis for the next gener... […]
New Stanford algorithm could improve diagnosis of many rare genetic diseases
on July 17, 2018 at 3:38 pm
Today, diagnosing rare genetic diseases requires a slow process of educated guesswork. Stanford computer scientist and genomicist Gill Bejerano, PhD, is working to speed it up. In a paper published re... […]
Fetal Gene Therapy Prevents Fatal Form of Gaucher Disease
on July 17, 2018 at 7:03 am
Study shows Gaucher disease can be prevented in mice following fetal gene therapy. [Cambridge University] Scientists have successfully delivered gene therapy directly to the brains of unborn mouse fet... […]
Fetal gene therapy could treat genetic diseases in the womb
on July 16, 2018 at 11:14 am
Emboldened by recent success stories of human gene therapy trials in children and infants, researchers are now pushing to treat diseases before birth. Some scientists are excited by the idea of using ... […]
Novel Therapies for Rare and Genetic Diseases 2018: Current Landscape and New Trends - Focus on Highly Interrelated and Synergistic Approaches
on July 16, 2018 at 10:26 am
The "Novel Therapies for Rare and Genetic Diseases" report has been added to ResearchAndMarkets.com's offering. Recent advancement in the development of novel platforms of smart targeting small molecu... […]
Swift Gene-Editing Method May Revolutionize Treatments for Cancer and Infectious Diseases
on July 12, 2018 at 6:33 am
A colored scanning electron micrograph of a white blood cell amid red blood cells. Researchers hope a new method to boost immune systems could make a treatment available to patients with almost any ty... […]
Yale scientists edit genetic diseases out of mice before birth; humans are next
on July 10, 2018 at 1:47 pm
Gene-editing techniques such as CRISPR/Cas9 can be used to astonishing, potential life-altering effect, such as one demonstration involving a possible treatment for ALS. Researchers at Carnegie Mellon ... […]
Mapping the genetic controllers in heart disease
on July 10, 2018 at 10:10 am
Researchers have developed a 3-D map of the gene interactions that play a key role in cardiovascular disease, a study in eLife reports. The map will help researchers identify the most important genes ... […]
via Google News and Bing News