Category Archives: Gene Medicine

Meeting a young patient with Zellweger syndrome, a rare, life-threatening genetic disease, started a scientific investigation that culminated with an unexpected discovery. The condition, also known as peroxisomal biogenesis disorder, had been linked only to lipid or fat metabolism. Now, as a team of scientists from several institutions, including Baylor College of Medicine, reveals in PLoS Genetics, the condition also affects sugar metabolism. The discovery of this connection in animal models can potentially lead to treatments that might improve the condition.

Meeting this patient at Texas Childrens Hospital inspired me to begin a research investigation to learn more about this disorder, said first and corresponding author Dr. Michael Wangler, assistant professor of molecular and human genetics at Baylor College of Medicine. The family of the patient found out about this research and offered to help. They started Zellfest, a fundraising event in San Antonio, Texas, that has partially supported our investigation. This led us to study this disorder in the fruit fly model in collaboration with the research team led by Dr. Hugo Bellen, professor of molecular and human genetics and investigator at the Howard Hughes Medical Institute at Baylor College of Medicine.

Peroxisomal biogenesis disorder results from defects in the genes that form the peroxisomes, essential micro-machines inside the cell that are involved in breaking down and producing certain lipids. When peroxisomes do not form, people develop a wide range of conditions that may include poor muscle tone, seizures, hearing and vision loss, poor feeding, skeletal abnormalities, as well as life-threatening problems in organs such as the liver, heart and kidney. There is no cure or treatment, other than palliative care.

Its been well established that several lipid pathways are altered in this disease; these are known peroxisomal functions, but there has been very little focus on other parts of metabolism. Everybody was thinking this was mainly a lipid disorder, Wangler said.

The researchers genetically engineered the laboratory fly, Drosophila, to lack two of the genes that are needed to make peroxisomes, PEX2 and PEX16, and then analyzed the flies metabolism.

We began a collaboration with Dr. James McNew, professor in biosciences at Rice University, who had started looking at flies using a metabolomics approach, Wangler said. Metabolomics is like taking a snapshot of all the metabolism of an organism by measuring hundreds of small molecules all at once, rather than focusing on one molecule at a time. We analyzed lipids, small carbohydrates, amino acids, cholesterol and small lipids. This approach gave us a general view of the metabolism of the organism.

The scientists found that the flies lacking the peroxisome genes had many of the problems observed in patients. The scientists learned, for instance, that these flies had short lives and locomotor problems. Their thorough analysis suggests that flies without PEX genes represent an animal model in which to further investigate the human condition.

In addition, we were surprised to discover that these flies were very sensitive to low-sugar diet, Wangler said. They cannot tolerate a low-sugar diet as well as normal flies; without sugar, flies without peroxisomes appear to be starving.

The researchers also applied a metabolomics approach to mice genetically engineered to lack a mouse PEX gene. As they had found in the flies, mice without peroxisomes also had alterations in the metabolism of sugars.

Our understanding is that the enzymes that break down sugars are not directly connected to peroxisomes, Wangler said. We are continuing our investigations and hope they will lead us to better understand how sugar metabolism is linked to peroxisomal biogenesis disorders.

Peroxisomes also play a role in common diseases such as Alzheimers and cancer, Wangler said. Studying this rare disease can help us understand peroxisomes better, and, in turn, that knowledge will help clarify the role of peroxisomes in Alzheimers and other disorders. Rare diseases can help understand issues that also contribute to more common diseases.

Other authors that contributed to this work include Yu-Hsin Chao, Vafa Bayat, Nikolaos Giagtzoglou, Abhijit Babaji Shinde, Nagireddy Putluri, Cristian Coarfa, Taraka Donti, Brett H. Graham, Joseph E. Faust, Ann Moser, Marco Sardiello and Myriam Baes. The authors are affiliated with one of more of the following institutions: Baylor College of Medicine, Texas Childrens Hospital, KU Leuven, Rice University and the Howard Hughes Medical Institute.

This work was supported by the Clayton Murphy Peroxisomal Disorders Research Fund at Baylor College of Medicine, National Institutes of Health K08 (NS076547) award to Michael Wangler, a grant by the Simmons Family Foundation to foster collaborative efforts between Rice University and Texas Childrens Hospital, awarded to Michael Wangler, Hugo Bellen and James McNew, as well as the support of Hugo Bellen, a Howard Hughes Medical Investigator.

View original post here:
Patient-inspired research uncovers new link to rare disorder - Baylor College of Medicine News (press release)

THURSDAY, June 22, 2017 (HealthDay News) -- Simple changes to your lifestyle might delay the start of dementia or slow its progression, a new report suggests.

Some scientific evidence indicates that keeping your mind active through "cognitive training," controlling your blood pressure and exercising more may pay dividends in terms of brain health, researchers determined.

Although not yet proven to thwart the cognitive decline that accompanies aging or dementia, the public should have access to this information, said Alan Leshner. He led the committee at the National Academies of Sciences, Engineering and Medicine that compiled the report.

"There are a few domains where the evidence that does exist suggests they might have an effect," said Leshner.

"At least two of those, we know, are good for a whole lot of other things that people do or that they could suffer from. That's controlling your blood pressure if you have hypertension and engaging in physical exercise," said Leshner, CEO emeritus of the American Association for the Advancement of Science.

Leshner's group was asked by the U.S. National Institute on Aging to research measures that might delay mild mental decline or Alzheimer's-like dementia.

Specialists welcomed the findings, which the researchers deemed encouraging even if not definitive.

"It's high time that people are given information about things they can do today to reduce their risk of cognitive decline and possibly dementia," said Keith Fargo, director of scientific programs and outreach at the Alzheimer's Association.

"Everyone is worried" about their mental functioning, he said. "But you shouldn't feel helpless. You should take control of your brain health," he added.

According to the report, which was released June 22, three promising areas for future research include:

He said the committee did not try to pinpoint which mental activities might be best; how low blood pressure should go; or how much exercise one needs to get the most benefit.

These are areas that need more research. Randomized trials are the "gold standard" of research and are the only ones that can prove or disprove a benefit from an intervention, he said.

One dementia specialist said some biological evidence supports the benefit of exercise, but in the final analysis, genetics might be the biggest determinant of whether you develop dementia.

"There is good evidence that physical exercise delays onset or slows progression [of dementia], perhaps because exercise stimulates release of nerve cell survival substances," said Dr. Sam Gandy. He directs the Center for Cognitive Health at Mount Sinai Hospital in New York City.

There is also good evidence that in people who carry the APOE4 gene mutation, which predisposes them to Alzheimer's, exercise can erase amyloid from their brains. Amyloid plaque is a hallmark of Alzheimer's disease, he said.

However, it's also possible that "genetic loading" for dementia is so strong in some people that diet and lifestyle will never be enough to prevent mental decline, he said.

Even without scientific backup for these lifestyle improvements, Leshner said they're worthwhile in their own right to improve other aspects of your health, such as preventing heart disease and strokes and improving the quality of your life.

"They're good for a whole bunch of other things," Leshner said.

Excerpt from:
Lifestyle Changes Might Prevent or Slow Dementia - Twin Falls Times-News

When the race to sequence the human genome was reaching a fever pitch in the early 2000s, when I was in high school, I couldnt help but wonder, What comes next? Once we had full access to our genetic blueprint, what more was there to do?

As it turned out, the understanding of human genetics is much more complicated than Id imagined as a teen. And understanding how human health hinges upon the strings of molecular letters within our DNA isnt always easy, either.

Researchers at Stanford, in collaboration with the biotechnology company Pacific Biosciences, are working to push past some of the limitations of current sequencing technology. Their goal is to make full-genome sequencing accessible for clinical use. The team has used a new sequencing technology called long-read sequencing in a patient for the first time. I described their work in a press release:

Current sequencing technologies cut DNA into words that are about 100 base-pairs, or letters, long, according to the studys senior author, Euan Ashley, DPhil, FRCP, professor of cardiovascular medicine, of genetics and of biomedical data science at Stanford. Long-read sequencing, by comparison, cuts DNA into words that are thousands of letters long.

This allows us to illuminate dark corners of the genome like never before, Ashley said. Technology is such a powerful force in medicine, he added. Its mind-blowing that we are able to routinely sequence patients genomes when just a few years ago this was unthinkable.

In this study, which appears in Genetics in Medicine, the team used long-read sequencing to examinea part of Ricky Ramons genes that hadnt been successfully sequenced with current technology. Ramon, who is 26, has had benign tumors throughout his body since he was about 7 years old, but doctors couldnt pinpoint a diagnosis. Especially problematic were the tumors in Ramons heart, which required open-heart surgery to remove.

The team thought Ramons symptoms were indicative of Carney complex, an extremely rare genetic condition, but the sequencing method they used initially did not identify any changes to the gene responsible.

Carney complex arises from mutations in the PRKAR1A gene, and is characterized by increased risk for several tumor types, particularly in the heart and hormone-producing glands, such as ovaries, testes, adrenal glands, pituitary gland and thyroid. According to the National Institutes of Health, fewer than 750 individuals with this condition have been identified.

The most common symptom is benign heart tumors, or myxomas. Open heart surgery is required to remove cardiac myxomas; by the time Ramon was 18 years old, hed had three such surgeries.

The long-read sequencing gave Ramons team of doctors at Stanford a confirmed diagnosis of Carney complex, which allows them to make better-informed recommendations about his treatment.

Though having confirmation of a permanent genetic condition can be disheartening at times, Ramon told me: Im in good hands Im glad to be here.

Previously: Clinical guidance on genetic testing: A Q&A, New tool to ID disease-causing genetic changes developed at Stanfordand Mystery solved: Researchers use genetic tools to diagnose young girls rare heart condition Photo by MIKI Yoshihito

Original post:
New genome sequencing method helps diagnose a rare genetic condition - Scope (blog)

NBCNews.com

FDA moves to clear path for drugs aimed at cancer-causing genes Lexington Herald Leader This represents some of the biggest opportunities in medicine to treat and cure debilitating and, yes, very costly diseases, Gottlieb wrote in remarks prepared for his appearance earlier this week before the Senate panel responsible for overseeing ... FDA Working to Lift Barriers to Generic Drug CompetitionFDA.gov all 19 news articles »

Follow this link:
FDA moves to clear path for drugs aimed at cancer-causing genes - Lexington Herald Leader

Its common to think of cancer as a disease driven by the buildup of mutations in the DNA of cells. Everything from pollutants to cigarettes to exposure to everyday chemicals can alter genes, and continued exposure over a lifetime can lead to a critical mass of mutations.

Now, researchers say the same process may be at work in heart disease. In a paper published in the New England Journal of Medicine, Dr. Sekar Kathiresan, from the Broad Institute of Harvard and MIT, and Dr. Benjamin Ebert from Brigham and Womens Hospital and their colleagues found a gene that builds up mutations over a lifetime and can double the risk of heart events.

MORE: Single Gene Responsible for Group of Heart Disease Risk Factors

While there are genes associated with greater heart disease risk, most of them are inherited. The new mutations linked to heart problems are among the first to be acquired, or picked up over a lifetime. The mutations develop among a group of blood cells known as stem cells, which divide throughout a person's lifetime to replenish the supply of blood cells. The genetic changes the researchers found are also linked to a higher risk of developing blood cancer, but they seem to have a stronger effect on heart disease than cancer.

This is a totally different type of risk factor than hypertension or hypercholestserolemia [high blood cholesterol] or smoking, says Kathiresan. And since its a totally different risk factor that works through a different mechanism, it may lead to new treatment opportunities very different from the ones we have for heart disease at present.

Kathiresan and his team actually found the gene several years ago when they linked it to a 10-fold higher risk of developing blood cancers. Although the mutations increased cancer risk, the cancers were still relatively rare, but people who had them had a 40% higher risk of dying of other causes. Among those was heart disease. In the new paper, the researchers looked at four different populations of nearly 8,000 people who had their genomes sequenced. Even among younger people, those with the mutationscalled clonal hematopoiesis of indeterminate potential, or CHIPshowed a higher rate of heart disease.

We were fully expecting not to find anything here, says Kathiresan. But the odds of having an early heart attack are four-fold higher among younger people with CHIP mutations.

MORE: This New Kind of Stem Cell May Revolutionize How We Treat Diseases

Whats significant about the CHIP mutations are that they arent inherited. They are accumulated over time, from exposures to all sorts of things that can damage DNA. Among people over 70, 10% of people have these mutations, says Kathiresan. Whether they develop heart problems (or cancer) depends on how many of the mutated cells are circulating in the blood. The load of mutations increases over time," Kathiresan says. "The higher the load, the more the risk of heart disease.

Fortunately, there are ways to detect the mutated cells. Currently available blood tests for blood cancers can easily keep track of the volume of mutated cells, which means that monitoring the CHIP mutations could be a new way to identify people at higher risk of having heart problems, keep track of their risk and guide treatments.

When the researchers introduced the CHIP mutations into mice, they learned more about how a cancer-causing gene can contribute to heart disease. It appears that the CHIP mutations cause atherosclerotic plaques in the blood vessels, which contributes inflammation and hardening of the arteries that can trigger heart attacks.

There's still a lot to learn. As exciting as the findings are, its still too early to add CHIP testing to routine blood screening to identify people at higher risk of having heart problems. And because CHIP contributes to heart disease in a new way, its possible that the mechanisms to control CHIP-related heart events have nothing to do with cholesterol, exercise and blood pressure. The mouse work suggests that the path to heart disease is something different from what we have been working on so far, says Kathiresan.

More work needs to be done to determine if there are ways to counteract the effect of the mutation on plaques or control the rate at which the mutations build up in these cells. Currently there isnt a drug thats safe enough or efficacious enough to treat people with, says Ebert. But its a very active area of research to identify interventions that can decrease the size of the mutated cell population or potentially eliminate them.

Originally posted here:
The Unexpected Way Genes Can Double Heart Disease Risk - TIME

SAN DIEGO The recent explosion in data generation combined with fast-improving analytic technologies are beginning to revolutionize the field of medicine and health care, bringing closer the era of precision medicine.

Precision medicine, also referred to as personalized or individualized medicine, is an emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment and lifestyle for each person, according to the US National Institutes of Health.

And its one of the hottest buzzwords in the medical biotech industry today, highlighted at the seminars and conferences that took place on the sidelines of the four-day Bio International Convention in San Diego from Monday to Thursday.

This may not come as a surprise, as San Diego is dubbed the genomics capital of the world for housing companies and academic institutions with strong capabilities in genomics, a field that involves mapping out the human gene to help understand and treat disease, as well as computing technologies.

If we can just do early predictions of heart disease and cancer (the two leading cause of death among men and women), we can have a profound effect on changing the longevity curve, Venter said as he presented the work of one of his companies, Human Longevity, at the conference on Thursday.

The San Diego, California-based company is compiling a large database of DNA and clinical information to find ways to extend the human lifespan by predicting disease.

It runs a $25,000 physical exam, dubbed the Health Nucleus which includes whole genome sequencing and whole body MRI imaging. The exam amasses personalized data totaling about one petabyte of medical information, analyzed via machine learning algorithms, to pinpoint signs of deadly diseases like cancer and Alzheimers.

So far, 103 people have received the exam, through which several have discovered cancer, brain tumors and liver disease that might otherwise have been left unnoticed and untreated, said the founding chairman of Human Longevity.

As the costs of genetic sequencing continue to freefall, personalized diagnostic services are expected to become more mainstream in the health care realm in the coming years.

Earlier this year, Illumina, the worlds biggest maker of DNA sequencing machines, introduced a new machine that is expected one day to allow for a genome to be sequenced for under $100. Less than a decade ago, full genome sequencing had cost several millions of dollars.

Academic institutions are engaged in similar efforts to amass a large collection of health data with the hope of developing an improved and more precise reference of human health.

Lloyd Minor, dean of the Stanford University School of Medicine shared how the university has partnered with the Duke University School of Medicine and Verily Life Sciences to initiate the Project Baseline study.

The study will enroll 10,000 participants and follow them for four years to collect data recorded via clinicians, self-reports and bio-specimen samples. This baseline map of human health will then be used to understand the transition from health to disease, according to Minor.

What will come out of this study can be used for biomarkers associated with new types of cancer, or a new novel area of the genome. That can then be tested in a larger group of people that are not undergoing a screen everything approach, he said.

Other panel discussions revolved around topics like the path from big data to precision medicine which addressed the challenges of translating the tsunami of genetic and biomedical imaging data into actionable knowledge for researchers, drug developers and clinicians.

Other eye-catching sessions revolved around the opportunities and challenges that artificial intelligence using computers to rapidly and intelligently analyze big data and generate insights poses on the biopharma value chain.

Organized by the Biotechnology Innovation Organization, the annual Bio International Convention is a major biotech and pharmaceutical industry event for networking, business meetings and seminars. This years edition took place for four days in San Diego.

By Sohn Ji-young, Korea Herald correspondent (jys@heraldcorp.com)

Visit link:
Data-driven personalized medicine takes center stage at US biotech conference - The Korea Herald

BBC News

The power of a billion: India's genomics revolution BBC News At the same time, there's a growing interest in developing new, more effective therapies tailored to an individual's genetic makeup - an idea known as precision or personalised medicine. Missing out on mapping worldwide genetic diversity is a big ... and more »

Read more from the original source:
The power of a billion: India's genomics revolution - BBC News

June 21, 2017 by Becky Freemal Treatments targeting a gene known as NLRX1 could help provide relief to the estimated 1.6 million Americans currently suffering from inflammatory bowel disease. Credit: Virginia Tech

Researchers at the Biocomplexity Institute of Virginia Tech have discovered a new therapeutic target for inflammatory bowel diseaseand it's right inside our immune cells.

The research at the Nutritional Immunology and Molecular Medicine Laboratory (NIMML), at the Biocomplexity Institute of Virginia Tech, targeted the gene known as NLRX1 as one that has potential therapeutic effects to aid in the treatment of gastrointestinal inflammation.

This investigation into how immunology and metabolism interface may hold critical answers for next generation nutritional immunology. The findings from the team's most recent research were published in the Journal of Immunology.

It's this sort of discovery that has the potential to customize healthcare for the individual, from personalized nutrition to precision medicine. The team uncovered new mechanistic insights into the role of NLRX1, targeting cellular metabolism and offering new therapeutic possibilities beyond traditional targets in autoimmune disease treatment.

"For decades, immunologists have applied reductionist approaches to studying the smallest details of the immune response without considering crucial system-wide interactions with nutrition and metabolism," said Josep Bassaganya-Riera, director of NIMML, a professor of immunology, and CEO of BioTherapeutics. "Our laboratory has built predictive computational and mathematical models and artificial intelligence pipelines capable of analyzing complex, massively interacting systems, including interactions between immunity and metabolism. This study not only elucidates novel mechanisms of immunoregulation in IBD, but it also validates transcriptomic and computational modeling studies that predicted the importance of NLRX1 in regulating gastrointestinal inflammation and its potential as a therapeutic target for infectious and immune-mediated diseases."

Due to an incomplete understanding of how NLRX1 works to decrease inflammation, scientific attempts to target this molecule as a treatment for the disease had previously stalled. The lab team's findings provide a deeper understanding of this gene's role in mucosal immunity and metabolism. This levels the playing field for both nutritional interventions that target NLRX1 and the development of NLRX1-based drugs.

"This seminal work, while impactful independently, sets the stage for the next lines of applied investigation on the role of NLRX1 in IBD," said Andrew Leber, scientific director of BioTherapeutics. "It highlights the need to understand not only the immediately relevant pathways for novel immunoregulatory genes, but their global effect on all of the cohesive metabolic and immunological processes within a cell, a goal that we will continue to pursue."

This work builds upon NIMML's successful track record in leading innovative transdisciplinary research at the interface of nutrition, immunity, and metabolism that dates back to its founding in 2002. The NIMML team has been involved in establishing spinoff companies that translate new scientific discoveries into the development of marketable products that address unmet consumer or clinical needs.

Explore further: Solving the immunity puzzle takes collaboration among different fields

More information: Andrew Leber et al. NLRX1 Regulates Effector and Metabolic Functions of CD4T Cells, The Journal of Immunology (2017). DOI: 10.4049/jimmunol.1601547

Studying the human immune system is like trying to work a vast, multidimensional jigsaw puzzle with pieces that are constantly changing shape. Billions of microbes interact with the host, shaping the processes that keep us ...

UNC Lineberger Comprehensive Cancer Center researchers have discovered that a deficiency in a key protein that regulates immune system warning signals could be a new biomarker for colorectal cancer, the second largest cancer ...

Scientists at the University of North Carolina (UNC) School of Medicine and Sanford Burnham Prebys Medical Discovery Institute (SBP) have identified a human (host) protein that weakens the immune response to HIV and other ...

The human immune system is a double-edged sword. While it is finely adapted to fighting potentially deadly viruses, such as the H1N1 influenza, the mechanisms it uses to fight pathogens can have negative effects such ...

Building on previous work with the botanical abscisic acida, researchers in the Nutritional Immunology and Molecular Medicine Laboratory (NIMML) have discovered that abscisic acid has anti-inflammatory effects in the lungs ...

The Nutritional Immunology and Molecular Medicine Laboratory (NIMML) research team at Virginia Tech has discovered important new information on the efficacy of conjugated linoleic acid (CLA) in treating Crohn's disease, a ...

Scientists from St. Jude Children's Research Hospital and Fred Hutchinson Cancer Research Center have developed an algorithm that functions like a Rosetta Stone to help decipher how the immune system recognizes and binds ...

Researchers at the Biocomplexity Institute of Virginia Tech have discovered a new therapeutic target for inflammatory bowel diseaseand it's right inside our immune cells.

A subpopulation of immune cells that normally fend off pathogens can turn against the host during certain infections, a new study publishing on June 20 in the open access journal PLOS Biology reveals.

In recent years, immunotherapy, a new form of cancer therapy that rouses the immune system to attack tumor cells, has captivated the public's imagination. When it works, the results are breathtaking. But more often than not ...

Exposure to sunlight releases a compound from the skin that can alleviate symptoms of eczema, research has found.

Racial discrimination experienced by African-American children and young adults exacerbates a type of asthma known to be resistant to standard treatment, according to a study headed by researchers at UC San Francisco.

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Read this article:
Researchers target gene to treat inflammatory bowel disease - Medical Xpress

SAN FRANCISCO, Calif. Mayo Clinic Ventures has partnered with a California-based company to make cancer-fighting gene therapies available to the public.

Vineti, a pioneering cell and gene therapy software and analytics company, announced Tuesday that it had completed its initial round of funding raising $13.75 million aimed at delivering "the first cloud-based software solution to improve patient access, accelerate life-saving treatment delivery, and promote safety and regulatory compliance for individualized cell therapies."

The funding was provided by Mayo Clinic Ventures, GE Ventures, DFJ and LifeForce Capital. It's just the 15th company that Mayo Clinic Ventures has backed since it was formed, according to Andy Danielson, vice chairman of Mayo Clinic Ventures.

"One thing with Vineti that we liked is that we have a commitment to cell and gene therapies at Mayo," Danielson told TechCrunch.com. "Vineti will make the gene and cell therapy production process more efficient and as a result, less costly. It's all part of the equation of making these therapies more affordable and opening them up to a greater number of people."

The targeted cancer therapy under development by Vineti is part of a thriving field that conducted more than 800 clinical trials in 2016 while investing nearly $6 billion. It's all aimed at positively impacting the oncology field, the largest market in medicine that's expected to grow to $165 billion by 2021.

The first two cell therapies are expected to hit the market later this year.

Vineti touts its plans as one that "integrates logistics, manufacturing and clinical data to improve product performance overall and enable faster, broader access for patients."

"Physicians, medical researchers and pharmaceutical companies are working together to develop successful therapies, transitioning from a one-size-fits-all model to individualized treatments for each patient," said Amy DuRoss, CEO at Vineti. "Now, the process for creating and delivering these treatments can be as innovative as the therapies themselves. We are developing the Vineti platform to help these treatments reach the patients who need them the most, and are confident the partnership between our advances technologies and leading medical research will deliver better outcomes across the globe."

See the rest here:
Mayo Clinic Ventures funds new cancer-fighting cell, gene therapy - Post-Bulletin

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 compellingpaper that presents a plausible and fascinatingmodel 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.

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.

See the rest here:
Thousands of genes influence most diseases - Stanford Medical Center Report