this is the search page

Scientists use advanced imaging to map uncharted area of genome

Using advanced imaging techniques, researchers at the University of Colorado Anschutz Medical Campus have mapped a previously uncharted region of the human genome that gives rise to a variety of disease, setting the stage to potentially test for the conditions in the future.

The study, published Sept. 3 in the journal Genome Research, was conducted by scientists at CU Anschutz led by Tamim Shaikh, PhD, the University of California San Francisco (UCSF) led by Pui-Yan Kwok MD, PhD and KU Leuven in Belgium led by Joris Vermeesch, PhD.

Dr. Tamim Shaikh, PhD, professor of pediatrics in the section of Genetics and Metabolism at CU School of Medicine.
Dr. Tamim Shaikh, PhD, professor of pediatrics in the section of Genetics and Metabolism at CU School of Medicine.

The research upends the view of many that the human genome was fully mapped in 2001 with the completion of the Human Genome Project.

“We have realized over time that this is not entirely true, as there are numerous gaps that remain in the reference human genome sequence,” said Shaikh, one of the senior authors of the study.  Shaikh is a professor of pediatrics in the section of Genetics and Metabolism at University of Colorado School of Medicine. “These gaps are present in regions that are unmappable and often `invisible’ to past and most current sequencing technologies.”

The researchers focused on a region on Chromosome 22, known as 22q11. There were numerous gaps in the sequence of this chromosome due to unmappable genetic sequences known as low copy repeats or LCRs.

LCRs are a significant source of genetic instability and can break chromosomes. That leads to a loss or gain of large pieces of DNA which can cause serious diseases. The loss of DNA in 22q11 leads to the 22q11 deletion syndrome resulting in symptoms which may include intellectual disability, dysmorphic features, heart defects, seizures, Autism spectrum disorders and schizophrenia.

Using two state-of-the-art genome mapping technologies known as fiber FISH and Bionano optical mapping, the researchers were able to see long DNA molecules and discover an unprecedented and extreme level of variability between individuals and populations. These differences can be hundreds of thousands to over two million base pairs of DNA.

“The large differences between people cannot be assessed without the mapping technologies deployed in this study,” said Dr. Pui-Yan Kwok, Henry Bachrach Distinguished Professor at UCSF, a collaborator of Dr. Shaikh who co-authored the paper. “Our approach brings clarity to the organization of the highly complex region studied.”

Shaikh agreed.

“You are mapping these chromosomal fragments back to the genome to see what is different,” Shaikh said. “We looked at over 150 apparently healthy people. We found the region in question was drastically different in each person.”

Some people carried far less and some far more DNA in this part of the genome.

Children with the 22q11 deletion syndrome and their parents were also tested to determine if their 22q11 LCRs were different.

“Now we can start asking questions like, `Is someone with more or  less DNA more disposed to have a child with disease?’” Shaikh asked. “If so, then it might be possible to genetically test parents before they have children.”

Shaikh said this region of the genome is constantly evolving.

“If you look from one generation to the next you may see changes within the same family,” he said. “That is pretty incredible.”

The study was funded multiple sources including a grant from the National Institutes of Health to Shaikh and Kwok.

 

The post Scientists use advanced imaging to map uncharted area of genome appeared first on CU Anschutz Today.

this is the search page

Researchers discover why intense light can protect cardiovascular health

Researchers at the University of Colorado Anschutz Medical Campus have found that intense light amplifies a specific gene that bolsters blood vessels and offers protection against heart attacks.

“We already knew that intense light can protect against heart attacks, but now we have found the mechanism behind it,” said the study’s senior author Tobias Eckle, MD, PhD, professor of anesthesiology at the University of Colorado School of Medicine.

The study was published today in the journal Cell Reports.

Tobias Eckle, MD, PhD, professor of anesthesiology
Tobias Eckle, MD, PhD, professor of anesthesiology

The scientists discovered that housing mice under intense light conditions for one week `robustly enhances cardio protection’, which resulted in a dramatic reduction of cardiac tissue damage after a heart attack. They also found that humans could potentially benefit from a similar light exposure strategy.

In an effort to find out why, they developed a strategy to protect the heart using intense light to target and manipulate the function of the PER2 gene which is expressed in a circadian pattern in the part of the brain that controls circadian rhythms.

By amplifying this gene through light, they found that it protected cardiovascular tissues against low oxygen conditions like myocardial ischemia, caused by reduced oxygen flow to the heart.

They also discovered that the light increased cardiac adenosine, a chemical that plays a role in blood flow regulation.

Mice that were blind, however, enjoyed no cardio protection indicating a need for visual light perception.

Next, they investigated whether intense light had similar effects on healthy human volunteers. The subjects were exposed to 30 minutes of intense light measured in lumens. In this case, volunteers were exposed to 10,000 LUX, or lumens, on five consecutive days. Researchers also did serial blood draws.

The light therapy increased PER2 levels as it did in mice. Plasma triglycerides, a surrogate for insulin sensitivity and carbohydrate metabolism, significantly decreased. Overall, the therapy improved metabolism.

Eckle has long known that light plays a critical role in cardiovascular health and regulating biological processes. He pointed out that past studies have shown an increase in myocardial infarctions during darker winter months in all U.S. states, including sunnier places like Arizona, Hawaii and California. The duration of the light isn’t as important as the intensity, he said.

“The most dramatic event in the history of earth was the arrival of sunlight,” Eckle said. “Sunlight caused the great oxygen event. With sunlight, trillions of algae could now make oxygen, transforming the entire planet.”

Eckle said the study shows, on a molecular level, that intensive light therapy offers a promising strategy in treating or preventing low oxygen conditions like myocardial ischemia.

He said if the therapy is given before high risk cardiac and non-cardiac surgery it could offer protection against injury to the heart muscle which can be fatal.

“Giving patients light therapy for a week before surgery could increase cardio protection,” he said. “Drugs could also be developed that offer similar protections based on these findings. However, future studies in humans will be necessary to understand the impact of intense light therapy and its potential for cardio protection.”

The post Researchers discover why intense light can protect cardiovascular health appeared first on CU Anschutz Today.

this is the search page

Scientists demonstrate the advantages of diverse populations when compiling genetic data

AURORA, Colo. (June 19, 2019) – Relying strictly on genetic data from those of European descent, rather than more diverse populations, can exacerbate existing disease and increase health care disparities, according to new research.

The research letter was published today in the journal Nature.

“There have been numerous discoveries in human genetics over the last few decades that have told us a lot about biology, but most of the work is being done on those of European descent,” said the study’s first author Christopher Gignoux, PhD, MS, associate professor at the Colorado Center for Personalized Medicine at the University of Colorado Anschutz Medical Campus. “By limiting our focus, we are limiting our understanding of the human genetics underlying complex traits. The PAGE Study gives us an overdue opportunity to look at what we can find when studying a large number of groups together.”

Associate Professor Chris Gignoux of the Colorado Center for Personalized Medicine.
Associate Professor Chris Gignoux of the Colorado Center for Personalized Medicine at CU Anschutz.

This was borne out in the study which examined thousands of individuals in the U.S. of non-European ancestry. The Population Architecture using Genomics and Epidemiology study (PAGE) was developed by the National Human Genome Research Institute and the National Institute on Minority Health and Health Disparities to conduct and empower genetic research in diverse populations.

Researchers genotyped 49,839 people and found a number of genetic variants replicated from studies strictly of European descent. But PAGE investigators found dozens of discoveries that would not have been possible in a single population study. This included both complex traits and in Mendelian, or monogenic disorders.

“In light of differential genetic architecture that is known to exist between populations, bias in representation can exacerbate existing disease and health care disparities,” the study said. “Critical variants can be missed if they have a low frequency or are completely absent in European populations…” Especially rare variants.

 

Kathleen Barnes, PhD, director of the Colorado Center for Personalized Medicine at CU Anschutz
Kathleen Barnes, PhD, director of the Colorado Center for Personalized Medicine at CU Anschutz

Gignoux said the success of precision medicine and genomics means recruiting people from underrepresented populations for genetic studies. Right now, those genomic databases lack critical diversity despite the fact that many of in underrepresented groups have the greatest health burden and stand to benefit the most from being included.

“The Colorado Center for Personalized Medicine on the Anschutz Medical Campus is committed to personalized medicine here in our state and region that will benefit ALL people, regardless of who you are or where you came from,” said Kathleen Barnes, PhD, director of the Colorado Center for Personalized Medicine. “Initiatives like PAGE, and the work summarized in this manuscript by Chris Gignoux and colleagues, show us the way forward in achieving our goals of inclusion. It also illuminates just how important genetic diversity is in our understanding of the architecture of genetic disease. These approaches can now feed into our personalized ancestry information resource for patients interested in their own ancestry, as well as benefit our research and clinical community.”

Gignoux agreed.

“With studies of diverse groups we got a better overall picture of the genetic architecture which show the underpinnings of disease,” Gignoux said. “We want to understand how genetics can improve and ameliorate disease rather than make it worse.”

The post Scientists demonstrate the advantages of diverse populations when compiling genetic data appeared first on CU Anschutz Today.

this is the search page

Sexual behavior may influence gut microbiome

A person’s sexual behavior could affect their microbiome and immune system, potentially elevating their risk of HIV infection, according to a new study from researchers at the University of Colorado Anschutz Medical Campus.

The study was published last week in the journal PLOS Pathogens.

Brent Palmer, PhD, associate professor of medicine in the Division of Allergy and Clinical Immunology at the CU School of Medicine
Brent Palmer, PhD, associate professor of medicine in the Division of Allergy and Clinical Immunology at the CU School of Medicine

The microbiome, a community of microbes in the gut, play a major role in driving and shaping the human immune system. But recent studies have shown that men who have sex with men (MSM) have very distinct microbiomes compared with men who have sex with women (MSW), regardless of HIV-infection status.

CU Anschutz researchers wanted to know whether this altered microbiome induces T cell activation associated with HIV transmission risk and increased disease severity.

To study this they took stool samples of 35 healthy men – men who had sex with men and men who had sex with women – and transplanted them into mice. The mice who received the MSM stool samples showed increased evidence of activation of CD4+ T cells, which would put them at a higher risk of HIV if they were human.

They also isolated immune cells from the intestines of HIV negative individuals and exposed them to bacteria from MSM and MSW feces. Human gut derived immune cells exposed to MSM fecal bacteria were more likely to be infected by HIV virus in vitro. This was again linked with increased immune activation by these fecal bacteria.

“These results provide evidence for a direct link between microbiome composition and immune activation in HIV-negative and HIV-positive MSM, and a rationale for investigating the gut microbiome as a risk factor for HIV transmission,” said the study’s senior author Brent Palmer, PhD, associate professor of medicine in the Division of Allergy and Clinical Immunology at the CU School of Medicine.

Exactly why the microbiome of men who have sex with men is so distinct remains unknown. Some have theorized that diet may promote inflammation and thereby activate T cells.

“There is a unique microbiome associated with men who have sex with men that drives immune activation in the gut that may also drive higher levels of HIV infection,” Palmer said. “But we still don’t know exactly why this is.”

Yet understanding this microbiome is important, Palmer said, because it could directly affect the immune system of high-risk men and lead to an increased risk of HIV infection.

The study co-authors include Sam X. Li, PhD, and Catherine Lozupone, PhD, of the University of Colorado Anschutz Medical Campus.

 

The post Sexual behavior may influence gut microbiome appeared first on CU Anschutz Today.

this is the search page

CU Anschutz researchers discover an important breakthrough in pulmonary fibrosis

A team of investigators led by members of the University of Colorado School of Medicine faculty at CU Anschutz Medical Campus has identified a connection between mucus in the small airways and pulmonary fibrosis.

The findings are published in Nature Communications.

David Schwartz, MD
David Schwartz, MD, chair of the Department of Medicine at the CU School of Medicine

“The overproduction of a lung mucin (MUC5B) has consistently been shown to be the strongest risk for the development of idiopathic pulmonary fibrosis (IPF) and most recently rheumatoid arthritis-interstitial lung disease,” said senior and corresponding author David Schwartz, MD, chair of the Department of Medicine at the CU School of Medicine.

Schwartz adds, “The findings in this manuscript provide a critical breakthrough in understanding the cause and potentially the treatment of IPF by demonstrating that excess mucus in the small airways can cause lung fibrosis, in part, by impairing the mechanism of lung clearance. In aggregate, these discoveries have provided the means to identify an at-risk population, diagnose the disease prior to the development of irreversible scarring, focus on a unique therapeutic target (MUC5B) and a specific location in the lung (distal airway), and create a novel pathway for therapeutic intervention for a disease that is currently incurable.”

A critical need for early diagnosis

Idiopathic pulmonary fibrosis is the most common type of progressive lung fibrosis. Over time, the scarring gets worse and it becomes hard to take in a deep breath and the lungs cannot take in enough oxygen. The average length of survival of patients with IPF is three to five years, and a critical unmet need is to identify patients before the lung is scarred irreversibly.

image of lungsMucociliary dysfunction is an emerging paradigm in lung diseases. Previously considered a characteristic specific to obstructive diseases such as asthma and chronic obstructive pulmonary disease, and genetic diseases such as primary ciliary dyskinesia and cystic fibrosis, the importance of mucins, mucus, and mucociliary interactions has surfaced in diseases of the lung periphery, such as adenocarcinoma and IPF.

Genetic findings may prevent progression

The investigators on the current study in Nature Communications hypothesized that the potential role for mucociliary dysfunction as a driver of IPF pathology is supported by unique gene expression signatures in IPF. The investigators found that a specific genetic characteristic, known as the MUC5B promoter variant rs35705950, which results in a marked increase production of mucus in the lung is the strongest genetic risk factor for IPF. They also found this is the strongest risk factor for rheumatoid arthritis-interstitial lung disease.

The findings suggest that targeting MUC5B in the terminal airways of patients with preclinical stages of interstitial lung disease represents a strategy to prevent the progression of preclinical pulmonary fibrosis.

“This study shows how genetic findings in human diseases can generate new hypotheses, such as those related to impaired mucociliary clearance, that may lead to the discovery of novel molecular mechanisms and the development of early diagnostics and more accurate treatments for pulmonary fibrosis,” said James P. Kiley, PhD, Director of the Division of Lung Diseases at the National Heart, Lung, and Blood Institute.

The research in the study is supported by Jennifer Matsuda, PhD, at National Jewish Health for generating Muc5b transgenic mice, Melanie Sawyer at Parion Sciences for assistance with in vitro mucolytic testing, and Jake McDonald at Lovelace Respiratory Research Institute for support with aerosol delivery. This research was supported by the National Heart, Lung and Blood Institute, National Institute of Diabetes and Digestive and Kidney Diseases, Department of Defense, Cystic Fibrosis Foundation HILL16XXO and BOUCHER15RO, and Parion Sciences, Inc.

The post CU Anschutz researchers discover an important breakthrough in pulmonary fibrosis appeared first on CU Anschutz Today.

this is the search page

Four sisters with cancer get care

Roberta Aberle and her three sisters share an unfortunate bond: cancer.

Her two oldest sisters passed away from the disease. She and one sister are still fighting the disease. All four sisters were diagnosed in their 40s or 50s, and all have received treatment through UCHealth – Aberle at the University of Colorado Cancer Center on the CU Anschutz Medical Campus and her sisters at Poudre Valley Hospital in Fort Collins.

“Our family is definitely satisfied in the care we’ve received,” said Aberle, 53, who lives in Aurora, where she can easily access treatment at CU Anschutz, “and I’m 100 percent confident in the care I’m getting right in my backyard.”

A former quality and process improvement professional for UCHealth, she now applies her skills as an advocate and resource for people with cancer. She’s spreading the word about the treatment she received from CU physicians, and her own story of cancer, far and wide.

Years of diagnoses

“Sadness took root in our family in 2005,” Aberle said. That was the year the first of her sisters, Brenda, received her cancer diagnosis.

Roberta Alberle
Roberta Alberle, CU Cancer Center patient

Brenda passed away in 2008, and a year later, sister Carol was diagnosed. Both Aberle and her oldest sister Debby got cancer diagnoses in 2012. Debby passed away six months after her diagnosis, but Aberle has survived, outliving her original prognosis by half a decade.

Aberle remembers Leap Day 2012 vividly. That was the day she went in for a quick assessment of a minor pain in her side. Despite her significant risk factors of having multiple first-degree relatives diagnosed with cancer before age 50, she never imagined a life-altering diagnosis.

“I was feeling healthy and energetic and working my dream job,” she said. “Nothing could have been going better at that time.”

She came out with a diagnosis of inoperable primary peritoneal cancer, one of the most rare and lethal forms of cancer, and recommendations to begin arranging for palliative and end-of-life care.

“I was in utter disbelief,” she said. “I had just been thinking how ill everyone in my family is and that I’m not prepared to be the person who outlives my entire family, and now I had cancer, too.”

While the disease has devastated the family, it has also mystified them. All four sisters have had reproductive cancers, but none the exact same type, and each has had a different outcome. Aberle shares the same genetic marker for cancer susceptibility with one of her sisters, but the other two sisters did not have the marker. And on top of everything, in 2015 their father was diagnosed with melanoma and lymphoma.

“Cancer has blown our family to bits,” Aberle said, “but a bit falls to the floor and we pick it up and glue it back on. It’s created a bond that can’t be broken.

A powerful treatment

Despite her family’s devastation and her own grim prognosis, Aberle was determined to fight her cancer. For the next year and a half, she underwent chemotherapy and entered clinical drug trials. Then, she received hyperthermic intraperitoneal chemotherapy (HIPEC), a rare cancer treatment that combines chemotherapy and surgery in a single procedure. The CU School of Medicine Department of Surgery is one of very few care providers in the United States that offer HIPEC.

During Aberle’s HIPEC treatment in 2013, CU surgeons opened her abdomen, removed the visible cancer cells and then doused the remaining cells with heated chemotherapy drugs. This procedure is followed by standard intraperitoneal (IP) chemotherapy. Because both HIPEC and IP techniques deliver chemotherapy directly to cancer cells in the abdomen (unlike systemic chemotherapy delivery, which circulates throughout the body), they can destroy microscopic cancer cells and has helped some patients live decades longer.

But it’s not an easy procedure for patients.

“It’s an invasive procedure, and it was a very difficult and painful recovery,” Aberle said. “I had a port inserted into my abdomen and staples up the length of my belly. Now, I have adhesions and scar tissue that still cause pain sometimes.”

Since HIPEC, Aberle’s cancer has returned, but she still believes it was the right treatment for her.

“It bought me additional time and got me farther down the path to the next available treatment,” she said. “I have no doubt in my mind that, if I had not had access to CU surgeons, I would not have survived this long.”

Survival on her own terms

Now five years into her battle with cancer, Aberle is still determined to fight the disease, and she’s grateful that the care providers at CU Anschutz continue to empower her to do that.

“My survival is 95 percent connected to the care I’m getting from the University of Colorado,” she said. “No one has ever relinquished their hope in me or objected when I say I want to keep going. It is phenomenal to be working with these doctors.”

Two years ago, Aberle took disability leave in order to devote more time and energy to conquering her cancer and to doing the things that are most important to her: spending time with loved ones and sharing her experience to help others.

“I’m not fooling myself that I’m going to live to 103,” she said. “There’s going to be a point when I want to go to palliative care and hospice, but I want to make my sure that we’ve done everything possible first. I know I’m with the right team at the CU Cancer Center, because they share in that philosophy right along with me.”

The post Four sisters with cancer get care appeared first on CU Anschutz Today.

this is the search page

Vitiligo researcher pushes limits in lab and in life

Richard Spritz on South Georgia island
Richard Spritz, MD, making the Shackleton Traverse, a trek across South Georgia island.

Geneticist Richard Spritz, MD, likes to be on the edge. Spritz, the Director of the University of Colorado School of Medicine’s (SOM) Human Medical Genetics and Genomics Program, loves the rush he gets from pushing his vintage Porsche 911 around a racetrack. He hikes in the Himalayas, and spent his most recent vacation trekking across a remote island, following the footsteps of famous Antarctic explorer Ernest Shackleton.

A career spent in a laboratory might seem less exciting, but not for Spritz. While he once was an accomplished mountain climber and survived two avalanches while backcountry skiing, he says his passion is not for taking risks—it is for the thrill of doing something new.

“I think that science is an incredibly adventurous thing. You’re always pushing beyond what’s known,” Spritz said. “I’m not an adrenaline junkie. Other people might call me that. I’ve just always been attracted to adventurous things.”

In Spritz’s eyes, there have been few bigger adventures in recent decades than the quest to understand  genetics and use that knowledge to cure diseases. After more than 40 years, he still marvels at how his career unfolded, and how far the science has come.

Fateful decisions

Spritz, 66, is one of the world’s leading vitiligo researchers. For almost two decades, he’s been conducting groundbreaking work understanding the genetics behind the skin pigmentation disorder that causes white patches to appear on the face, body and hair. An estimated 50 million people worldwide have the condition.

Spritz didn’t set out to become a geneticist. Two decisions he made while he was still a self-described “brash young man” shaped the course of his career.

Richard Spritz car
Among Spritz’s hobbies is racing his vintage Porsche 911

Spritz is from Philadelphia, but he felt the mountains’ call at a young age, and he became an accomplished mountain climber in his youth. Successful ascents in the Alps, including the notoriously dangerous north face of the Eiger, earned him the respect of the climbing elite, and in the 1970s he was invited to join an expedition to climb Mount Everest.

Spritz declined because he was in medical school and did not want to disrupt his career. “I absolutely made the right choice,” he said.

“It’s mostly out of my system,” Spritz said. But he’s not through going on adventures, and last fall he hiked across South Georgia, an island near Antarctica. Peter Hillary and Jamling Tengzing Norgay, the sons of the first two men to climb Everest, were on the trek. They were filming a documentary for National Geographic about Shackleton, who had to cross the mountainous island to rescue his stranded crew. In the company of climbing royalty, it was natural to think about Everest, but Spritz saw the risk.

“I’m 66 years old. While I’m not like most 66-year-olds, I know I could get high enough to get into real trouble,” Spritz said. Now, he gets his thrills through amateur auto racing, which he points out is far safer than climbing or extreme skiing. His next trip will be to the Himalayas for another trek.

Spritz made his second career-defining decision “literally one day while walking down the street,” he said. He had planned to become a surgeon and had made arrangements to start down that path, but realized genetic research was a better fit for someone seeking to push scientific boundaries.

“I was incredibly lucky, because I did that at exactly the right moment in history, at the beginning of recombinant DNA research,” Spritz said. “I was lucky to get in on the ground floor.”

It led to a fruitful career. In the late 1970s, researchers were just discovering how to isolate, identify and sequence human genes. The biggest early discovery Spritz was part of was finding and sequencing a mutation that affects hemoglobin, the molecule that carries oxygen in the blood. It was the first time a mutation had been sequenced.

Still making discoveries

“Despite the fact that vitiligo has been known for hundreds of years, there’s never been a drug developed for it,” Spritz said. “That might change in the near future.”

Spritz has not stopped researching—or making discoveries. In October, Spritz and his lab published a paper in Nature Genetics finding 23 genes linked to susceptibility for vitiligo. The lab tested 4,680 people with the condition and 39,586 control cases. The study attracted the attention of pharmaceutical companies, which Spritz said is good news because a medication to treat vitiligo could be a major step forward from the current steroid and ultraviolet light treatments.

“Despite the fact that vitiligo has been known for hundreds of years, there’s never been a drug developed for it,” Spritz said. “That might change in the near future.”

Much more research would be needed before a drug could be developed, and then it would have to go through rounds of safety and efficacy testing. Spritz said enough work has been done that complex relationships between genes “are coming together in a way that kind of makes sense,” which has allowed vitiligo researchers to “leap frog” ahead faster than Spritz expected.

People with other conditions might benefit as well. In the mid-2000s, Spritz established that vitiligo was an autoimmune disease, in which the body attacks its own skin pigmentation cells. Research has shown people susceptible to vitiligo have increased odds of other autoimmune conditions such as Type I diabetes, rheumatoid arthritis and Addison’s disease. Vitiligo research could lead to progress understanding those conditions, and vice versa.

That would be the next chapter in an ongoing scientific adventure.

“It’s amazing to me how far we’ve come, how naïve we were and yet how prescient we were at the same time,” Spritz said. “We are asking and answering the kinds of questions we couldn’t have imagined when I was a student. I think that’s incredibly inspirational – and we’ve hardly started.”

The post Vitiligo researcher pushes limits in lab and in life appeared first on CU Anschutz Today.

this is the search page

Researchers find association between gene mutation and rare heart disease

A strong association between a genetic mutation and a rare kind of heart muscle disease has been discovered by researchers at the University of Colorado Anschutz Medical Campus.

The finding, published this week in the Journal of the American College of Cardiology, could improve understanding of the disease and lead to new treatments.

Teisha J. Rowland, PhD, a post-doctoral fellow in the lab of Luisa Mestroni, MD, and Matthew R. G. Taylor, MD, PhD, at the University of Colorado School of Medicine
Teisha J. Rowland, PhD, a post-doctoral fellow in the lab of Luisa Mestroni, MD, and Matthew R. G. Taylor, MD, PhD, at the University of Colorado School of Medicine.

“There are many kinds of cardiomyopathies that can lead to heart failure so this is a serious problem,” said Teisha J. Rowland, PhD, a post-doctoral fellow in the lab of Luisa Mestroni, MD, and Matthew R. G. Taylor, MD, PhD, at the University of Colorado School of Medicine and first author of the study.

The Mestroni and Taylor lab sequenced nearly 5,000 genes in 335 patients with a family history of heart muscle disease, looking for mutations that could cause a variety of cardiomyopathies.

“Many kinds of heart disease are caused by genetics. When that happens, the disease is often more severe and happens at an earlier age,” said Rowland, who studies genetics and cardiology. “So we look at the DNA in entire families to see what sort of genetic variants those with the illness have in common.”

They found that several people with left ventricular noncompaction (LVNC) had a mutation in a gene called Obscurin. Obscurin is part of the sarcomere, the basic unit of striated muscles that pull and glide past each other when muscles contract.  That includes the heart muscle. If there is a mutation in Obscurin that process may not function properly.

Image of human heart
A strong association between a genetic mutation and a rare kind of heart muscle disease has been discovered by CU Anschutz researchers.

“We found a strong association between this gene, which has not been studied much, and this rare form of genetic heart disease,” Rowland said. “Left ventricular noncompaction is thought to happen during early human development. It would be interesting to see if mutated Obscurin affects heart formation during development.”

Rowland said the findings point to areas warranting further attention.

“We expect this will ultimately improve our understanding of the disease,” she said.

The other authors include: Sharon L. Graw, PhD; Mary E. Sweet, BA; Matthew R.G. Taylor MD, PhD and Luisa Mestroni, MD all of the Cardiovascular Institute and Adult Medical Genetics Program at the University of Colorado Anschutz Medical Campus.

And Marta Gigli, MD, of the collaborating research group at the Cardiovascular Department, University of Trieste Hospital and SOM, Trieste, Italy.

 

 

The post Researchers find association between gene mutation and rare heart disease appeared first on CU Anschutz Today.