Category Archives: Genetic Medicine

CHAPEL HILL Scientists at the UNC School of Medicine and colleagues created a new computational tool called H-MAGMA to study the genetic underpinnings of nine brain disorders, including the identification of new genes associated with each disorder.

The research,published inNature Neuroscience, revealed that genes associated with psychiatric disorders are typically expressed early in life, highlighting the likelihood of this early period of life as critical in the development of psychiatric illnesses. The researchers also discovered that neurodegenerative disorder-associated genes are expressed later in life. Lastly, the scientists linked these disorder-associated genes to specific brain cell types.

By using H-MAGMA, we were able to link non-coding variants to their target genes, a challenge that had previously limited scientists ability to derive biologically meaningful hypotheses from genome-wide association studies of brain disorders, said study senior authorHyejung Won, PhD, assistant professor of genetics at the UNC School of Medicine and member of the UNC Neuroscience Center. Additionally, we uncovered important biology underlying the genetics of brain disorders, and we think these molecular mechanisms could serve as potential targets for treatment.

Hyejung Won, PhD UNC photo)

Brain disorders such as schizophrenia and Alzheimers disease are among the most burdensome disorders worldwide. But there are few treatment options, largely due to our limited understanding of their genetics and neurobiological mechanisms. Genome-wide association studies (GWAS) have revolutionized our understanding of the genetic architecture related to many health conditions, including brain-related disorders. GWAS is a technique that allows researchers to compare genetic sequences of individuals with a particular trait such as a disorder to control subjects. Researchers do this by analyzing the genetic sequences of thousands of people.

To date, we know of hundreds of genomic regions associated with a persons risk of developing a disorder, Won said. However, understanding how those genetic variants impact health remained a challenge because the majority of the variants are located in regions of the genome that do not make proteins. They are called non-coding genetic variants. Thus, their specific roles have not been clearly defined.

Prior research suggested that while non-coding variants might not directly encode proteins, they can interact with and regulate gene expression. That is, these variants help regulate how genes create proteins, even though these variants do not directly lead to or code for the creation of proteins.

Given the importance of non-coding variants, and that they make up a large proportion of GWAS findings, we sought to link them to the genes they interact with, using a map of chromatin interaction in the human brain, Won said. Chromatin is the tightly packed structure of DNA and proteins inside cells, folded in the nucleus in a way to maintain normal human health.

Won and colleagues used this map to identify genes and biological principles underlying nine different brain disorders, including psychiatric conditions such as schizophrenia, autism, depression, and bipolar disorder; and neurodegenerative disorders such as Alzheimers, Parkinsons, amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS).

Using the computational tool H-MAGMA, Won and colleagues could link non-coding variants to their interacting genes the genes already implicated in previous GWAS findings.

Another important question in brain disorders is to identify cellular etiology the cells involved in the root cause of disease. This is especially critical as the brain is a complex organ with many different cell types that may act differently in response to treatment. In the attempt of finding critical cell types for each brain disorder, the researchers found that genes associated with psychiatric disorders are highly expressed in glutamatergic neurons, whereas genes associated with neurodegenerative disorders are highly expressed in glia, further demonstrating how the two disorder clusters diverge from each other.

Moreover, we classified biological processes central to the disorders, Won said. From this analysis, we found that the generation of new brain cells, transcriptional regulation, and immune response as being essential to many brain disorders.

Won and colleagues also generated a list of shared genes across psychiatric disorders to describe common biological principles that link psychiatric disorders.

Amongst the shared genes, we once again identified the brains early developmental process as being critical and upper layer neurons as being the fundamental cell-types involved, Won said We unveiled the molecular mechanism that underscores how one gene can affect two or more psychiatric diseases.

H-MAGMA is publicly available so that the tool can be widely applicable and available to the genetics and neuroscience community to help expand research, with the ultimate goal of helping people who suffer with brain-related conditions.

The National Institute of Mental Health, the Brain and Behavior Research Foundation, and the Simons Foundation Autism Research Initiative funded this research.

Other authors were Nancy Sey, Benxia Hu, Won Mah, Harper Fauni, Jessica McAfee, all from UNC-Chapel Hill, and Prashanth Rajarajan, Kristen Brennand, and Schahram Akbarian from Mount Sinai Health System.

(C) UNC-Chapel Hill

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New UNC computational tool boosts understanding of genetic disorders affecting the brain - WRAL Tech Wire

March 11, 2020 -Henry Ford Health System has received a $25 million grant to accelerate its precision medicine program, with the ultimate goal of creating a Precision Health Center.

With the donation, Henry Ford will focus on advancing cancer research and treatment, as well as precision therapies for behavioral health, cardiovascular conditions, and metabolic diseases.

Henry Ford received the gift from developer Chris Jeffries and his wife Lisa. The donation is the largest single gift from an individual in the health systems 105-year history.

We are incredibly grateful to Lisa and Chris Jeffries for their generosity, saidWright Lassiter, III, president and CEO of Henry Ford Health System.

We are experiencing a momentous era in medicine, a radical shift from the traditional approach to cancer care. This gift will help us consolidate and advance our collective efforts to create unprecedented access to advanced, highly personalized treatments for our patients and members.

The grant will significantly boost the health systems translational research efforts, which quickly transforms the most innovative discoveries in the lab into new treatments for patients.

Translational research is a significant differentiator of our clinical programs at Henry Ford and is a critical element to help us treat many of the most challenging conditions our patients face, saidAdnan Munkarah, MD, executive vice president and chief clinical officer of Henry Ford Health System.

Translational research is bench-to-bedside, meaning it allows patients to benefit from discoveries in real time. That is an essential part of our history and commitment to medicine and academics not only offering the latest innovations in medicine, but also playing a leading role in their development.

The donation will build on the organizations past work to advance precision medicine and personalized care. In October 2017, Henry Ford Health System launched the Henry Ford Cancer Institute, a facility focused on ambulatory cancer treatment, precision medicine, clinical trials and research, and enhanced support services for cancer patients.

With the grant, researchers will be able to continue to develop individualized therapies for cancer and other conditions.

By analyzing genetic and non-genetic factors, we can gain a better understanding of how a disease forms, progresses and can be treated in a specific patient, saidTom Mikkelsen, MD, medical director of the Precision Medicine Program andClinical Trials Officeat Henry Ford Health System.

As of now, we can check for more than 500 genomic markers, which helps us understand the pattern of changes in a patients tumor cells that influence how cancer grows and spreads. Im confident this gift will lead to advancements that provide hope for patients with even the most complex diagnoses.

The Henry Ford Cancer Institute has one unified team of cancer specialists working to deliver personalized cancer treatments. The Institute includes five hospital locations, six additional outpatient cancer centers, and dozens of aligned doctors offices.

Even a decade ago, our approach to treating brain cancer was Precision Medicine before anyone knew what Precision Medicine was, said Steven Kalkanis, MD, CEO of Henry Ford Medical Group and Henry Fords chief academic officer.

In the time since, weve seen a significant increase in the number of brain cancer patients who are outliving their prognoses, due in large part to clinical innovation. Our relentless pursuit of clinical breakthroughs has more momentum now than at any other point in history.

The new grant will only serve to accelerate precision medicine in care delivery.

The support of our donors is the fuel behind our clinical innovations and the breakthroughs that are improving peoples lives, saidMary Jane Vogt, senior vice president and chief development officer at Henry Ford Health System. It is remarkable to work with donors who believe in a better tomorrow and the power of a unified approach to medicine.

The donation is expected to help drive innovations in treating brain, lung, pancreatic, and colon cancers, as well as other chronic diseases like cystic fibrosis, asthma, and heart disease.

The team at Henry Ford is second to none, said Chris Jeffries. We believe this gift will lead to other families having more time together. Defeating cancer requires a concerted effort from everyone and we hope to make as big an impact on that goal as possible.

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Henry Ford Receives $25M Grant to Expand Precision Medicine Program - HealthITAnalytics.com

What would the implications be if decoding your genes cost less than a pair of designer jeans? We might soon find out after a Chinese company claimed it can sequence the human genome for $100.

The speed at which the price of genetic sequencing has fallen has been astonishing, from $50,000 a decade ago to roughly $600 today. For a long time, the industry saw the $1,000 genome as the inflection point at which we would enter the genomic agewhere getting a read out of your DNA would be within reach for huge swathes of the population.

That milestone has come and gone, but progress hasnt stopped. And now Chinese firm BGI says it has created a system that can sequence a full genome for just $100. If the claims hold up, thats a roughly six times improvement over state-of-the-art technology.

The key to the breakthrough is a significant increase in the size of the chip that is used to analyze genetic data, so twice as many genomes can be processed at once. Their machine also uses a robotic arm to dunk the chip into baths of the chemicals used to carry out the sequencing process, which allows them to be reused multiple times.

The company says the system, which will be made available to customers late this year, is aimed at large-scale genomics projects and could make it possible to decode the DNA of 100,000 people a year.

The breakthrough could spur further price falls as well by breaking the stranglehold that industry leader Illumina has had on the market. Dennis Grishin, co-founder of startup Nebula Genomics, told MIT Tech Review that he believed the reason the price of genetic sequencing had remained stuck around $1,000 in recent years was due to Illuminas near monopoly.

A $100 genome could significantly broaden the scope of what we can do with genetic data. The growing field of population genetics promises to uncover the genetic quirks that set different groups of people apart, which can prove vital for developing new medicines and understanding the susceptibility of different groups to certain conditions.

While some ambitious projects, such as the UK Biobank project aimed at collating genetic data on 500,000 people, are already underway, the cost of sequencing has so far limited the scope of these projects. A dramatically cheaper system could see these kinds of initiatives become far more commonplace, greatly expanding our understanding of genetic diversity among humans.

By bringing the cost of full genome sequencing within reach of everyday people, the approach could also dramatically expand the scope of personalized medicine. While services like 23andMe have seen a huge expansion in consumer genetic testing, these services only decode a small fraction of the genome that isnt particularly useful for medical purposes.

DNA sequencing is already used to tailor cancer treatment by determining how peoples genetics are likely to influence their response to certain treatments, but it is still far from standard practice. At $100 the practice could become far more common and also be expanded to predict responses to a host of other treatments, ushering in a new era of personalized medicine.

Theres also hope that it would enable new tests that could provide early warning of susceptibility to a host of genetic diseases, or even sequence the DNA of patients microbiomes to detect imbalances in their gut flora that might be responsible for certain conditions or impact their responses to certain treatments.

Rade Drmanac, chief scientific officer of Complete Genomics, a division of BGI, told MIT Tech Review that at $100 it could soon be common to sequence the DNA of every child at birth. This could provide unprecedented early-warning for a host of diseases, but would also open up a Pandoras box of ethical concerns.

The movie Gattaca already explored the potential for discrimination when genetic testing becomes trivially easy, particularly when paired with increasingly powerful genetic engineering that is bringing the potential for designer babies ever closer.

Perhaps more importantly though, our understanding of how our genetics impact our lives is still very hazy. While we have identified some genes that strongly influence propensity for certain diseases, most human characteristics are governed by complex interactions between multiple genes whose activity can vary throughout our lives in response to environmental pressures.

Our ability to read our DNA is far ahead of our ability to understand it, which could lead to all sorts of problemsfrom creating a new class of worried well flagged as at risk of certain conditions that never come to be, to unnecessarily medicalizing or stigmatizing patients in ways that alter the trajectories of their lives.

With a $100 genome now within reach, we will have to tackle these issues with urgency to make sure the genomic age is one to look forward to rather than one to fear.

Image Credit: Pete Linforth from Pixabay

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$100 Genome Sequencing Will Yield a Treasure Trove of Genetic Data - Singularity Hub

CALGARY -- When Madden Ellis Garraway was just under two-years-old, he became very sick.

His skin was so dry it bled and he couldnt hold down food, causing his weight dropped to within ounces of his birth weight of seven pounds, six ounces.

Doctors struggled to figure out what was wrong.

We had a large list of things that we were thinking of, and our immunology team and my colleagues who are working with Madden were having trouble arriving at the right one," said Dr. Francois Bernier, head of the Department of Medical Genetics and a professor in the Department of Paediatrics at the University of Calgary's Cumming School of Medicine.

"In fact, we made some attempts to arrive at a diagnosis but we're still unsure. It took a while.

Doctors often struggle with diagnosing unusual health issues, especially those that may require genetic testing.

They often must rely on genome sequencing tests to determine the root cause of a disease and until now, large-scale genome sequencing tests were often sent to labs in the United States for analysis.

Bernier calls it "the diagnostic odyssey," a long, difficult, journey for families waiting while cliniciansfigure out what is causing the underlying health issues.

Madden Garraway in hospital at the age of two. (Photo courtesy the Garraway family)

Maddens family can attest to that.

It was months of waiting, wondering and worrying before Madden's blood was sent to a U.S. lab for genome analysis, where it was learned he suffered from a rare genetic condition called immune dysregulation polyendocrinopathy enteropathy X-linked (IPEX) syndrome.

IPEX is a rare genetic disorder that can be life threatening.

"If we could have learned about that instantly, or within the several weeks that we can do now, that will save a lot of time," said Maddens father, Patrick Garraway.

"We could have got on with his bone marrow transplant sooner."

Madden received a bone marrow transplant from his sister. Now five-years-old, the playful youngster has made a full recovery and no longer requires medication.

"There are so many families waiting for answers to serious medical conditions," said Bernier.

"Access to gene sequencing early in the medical journey can pinpoint the best treatment approaches and therapies to target the illness."

Madden Garraway today at the age of five. (Photo courtesy the Garraway family)

A new partnership struck between the University of Calgary, University of Alberta, and Alberta Precision Laboratorieswill help families and medical professionalsanswer to those diagnostic puzzles sooner.

The partnership is funded by Genome Canada, the Alberta Childrens Hospital Foundation, and other partners. Four other centres in Canada are also undertaking similar programs through Genome Canadas funding, one in B.C., two in Ontario and one in Quebec.

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Rapid genetic testing becomes available to Calgary medical community - CTV News

Growing up on a farm near the small community in of Fordyce in Northeast Nebraska, David Steffen dreamed of one day becoming a country vet.

His family raised cows, sows and broilers, and he got to know the country veterinarians who tended to the livestock of his family and his neighbors. Their days seemed interesting and varied, Steffen said. Veterinarians helped both animals and the people who cared for them. All of these things appealed to Steffen.

He attended college at the University of Nebraska-Lincoln, where he studied animal science. After graduation, he went on to Iowa State University, where he got his DVM.

For a few years, he did become a country vet. But his wife, whose expertise was in computers, had a difficult time finding a job, and Steffen began looking for a position someplace where she could put her degree to work, too. He and his wife moved to Manhattan, Kan., where he began work on a doctoral degree at Kansas State University. This put him on track for an academic career, with a stop at North Dakota State University before he returned to Nebraska.

Today, he provides leadership in diagnostic pathology and as the quality control section head of the veterinary diagnostic center. And recently, he received the highest honor in the field of veterinary diagnostics the 2019 Dr. Edward P. Pope Memorial Award, presented by the American Association of Veterinary Laboratory Diagnosticians.

The award was a huge honor and came as somewhat of a surprise to Steffen, whose favorite part of the job remains helping people.

On a recent morning in his office in the Veterinary Diagnostic Center, he looked at slides from feeder lambs that were succumbing to a mystery affliction, as well as from a Scottish terrier with a terrible looking liver. Steffen finds it rewarding to figure out a diagnosis for a livestock producer whose livelihood is affected by disease, or for a pet owner who wants to know why their pet is sick.

It is a blessing to work using scientific knowledge to help others, Steffen said in a story about the award in the Journal of Veterinary Diagnostic Investigation. Every day I am provided the opportunity to develop meaningful, productive relationships with clients and scientists as we partner to improve the economic vitality of animal agriculture, the emotional health of pet owners, and the general health of animal populations and all people.

No two days are quite alike, and Steffen enjoys that, too.

You get to see all kinds of weird, interesting stuff, he said. You get to be a detective.

One particularly interesting mystery he encountered was a fatal type of dwarfism that showed up in several different breeds of calves. Steffen was able to pinpoint a genetic cause for the disease, which ultimately allowed for development of a test for breeders. Over his career, Steffen was able to identify seven different genetic disorders all of which led to the development of tests that livestock producers can use to determine whether their animals are afflicted.

With genomics now, we can go from recognizing a disease to having a test for it within a year, he said.

Throughout his career, he has dedicated time and expertise to advance animal health and veterinary pathology at state and national levels, serving on the Nebraska Poultry Health Committee, the Nebraska State Lab Response Network, and the Johnes Disease Committee. He has been a member of the American association of Veterinary Laboratory Diagnostics since 1996, over the years serving as both vice president and president. He also served as an associate editor for the Journal of Veterinary Diagnostic Investigation. He has author or co-authored more than 60 peer-reviewed publications on topics including diagnostics, comparative medical sciences and many other issues and received numerous other awards. He also served as an undergraduate adviser for more than a decade, and has kept in contact with many of his old students.

Dave has made many significant contributions to animal health, livestock management and veterinary pathology, said Ron Yoder, associate vice chancellor for the Institute of Agriculture and Natural Resources at the University of Nebraska-Lincoln. We highly value his work here at the university, as do livestock producers across Nebraska and the country.

Steffen didnt imagine that his plan to be a country vet would have led him down the path it did. But the things that drew him into vet medicine in the first place the variety, the opportunity to meet people and to help them have remained central throughout his career. Hes more likely, though, to do so from his office than on a farm like the one where he grew up.

My happy place is here at my microscope, he said.

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Veterinary Medical and Biomedical Sciences Professor David Steffen honored with top industry award - Fence Post

An undeclared civil war is breaking out in biomedicine.On one side is precision medicine, with its emphasis on tailoring treatments to ever-narrower groups of patients. On the other side is population health, which emphasizes predominantly preventive interventions that have broad applications across populations.

Which vision will provide the most durable and efficient path to improved health for all?

Disregarding the breakthrough announcements that appear on a regular basis, the question of whether precision medicine will lead to better health for all remains an open one.

We believe that genomics and precision medicine have ridden a wave of hype without substance for far too long. Unless they are able to go well beyond their thin record of empirical success and demonstrate their effectiveness in meeting the actual health needs of populations, they will be marginal players with regard to any lasting impact on the health of the public.

Fortunately, it appears that the tide is beginning to turn toward population health, especially as a more balanced perspective of the value ofpolygenic risk scores one of the most widely advocated innovations of the precision medicine movement is beginning to emerge.

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Viewpoint: Promise of genomics and precision medicine a 'wave of hype without substance' - Genetic Literacy Project