StemCell Therapy

Genome-wide association study identifies ABO blood protein

The identification of a gene cluster associated with progression to severe disease in patients with Covid-19 strengthens findings from earlier studies suggesting a prominent role for ABO blood group locus in disease severity.

In the genome-wide association study (GWAS) involving patients hospitalized with Covid-19 in Italy and Spain during the local peak of the pandemic, patients with blood group A had an increased risk for progression to severe disease, while patients with blood group O had a lesser risk for progression.

The strongest signal for severe disease, however, was the rs11385942 insertion-deletion GA or G variant at locus 3p21.31, according to researchers from the Severe Covid-19 GWAS Group.

Blood-group specific analysis showed a higher risk for severe disease among patients with blood group A and a lower risk with blood group O.

The groups findings, published Oct. 14 in the New England Journal of Medicine, were originally reported online in June.

In a newly published commentary, researcher Arthur Kaser, MD, of the University of Cambridge Institute of Therapeutic Immunology and Infectious Disease wrote that the genome-wide association study represents a major leap toward disentangling the molecular mechanisms that cause severe Covid-19.

Kaser was not involved with the study.

This genome association study will set directions for research, he wrote, adding that a focus on the immunologic synapse between T cells and antigen-presenting cells appears to be warranted in the search for therapies to address the hyperinflammatory state known as cytokine storm that occurs in some patients with severe Covid-19.

Researchers from the Severe Covid-19 GWAS Group pragmatically compared data from patients hospitalized with severe Covid-19 (defined as respiratory failure), with data from contemporarily recruited blood donors with mostly unknown SARS-CoV-2 status and from historically healthy controls from the same region.

Associations were identified between the risk of developing severe Covid-19 and a multigene locus at 3p21.31 and the ABO blood group locus at 9q34.2.

No association signal was shown for the human leukocyte antigen (HLA) region, which is a regulator of infection immunity and has been suggested as a potential driver of Covid-19 severity.

At locus 3p21.31, the association signal spanned 6 genes: SLC6A20, LZTFL1, CCR9, FYCO1, CXCR6 and XCR1.

The association signal at locus 9q34.2 coincided with the ABO blood group locus; in this cohort, a blood-groupspecific analysis showed a higher risk in blood group A than in other blood groups (odds ratio, 1.45; 95% CI, 1.20-1.75; P=1.48104) and a protective effect in blood group O as compared with other blood groups (odds ratio, 0.65; 95% CI, 0.53-0.79; P=1.06105), wrote Tom H. Karlsen of the University of Oslo, and colleagues from the Severe Covid-19 GWAS Group.

In his editorial, Kaser noted that among the 6 candidate genes at 3p21.31, LZTFL1 might be the most compelling, with the rs11385942 variant and all other fine-mapped association signals that exceeded genome-wide significance located within it.

LZTFL1 is widely expressed and encodes a protein involved in protein trafficking to primary cilia, which are microtubule-based subcellular organelles acting as antennas for extracellular signals, he wrote. In T lymphocytes, LZTFL1 participates in the immunologic synapse with antigen-presenting cells, such as dendritic cells (these cells prime T-lymphocyte responses).

Kaser noted that of the other 5 candidate genes, 4 (CCR9, FYCO1, CXCR6 and XCR1) have roles in T-cell and dendritic-cell function, while SLC6A20 is a transporter with intestinal expression regulated by the SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2).

Earlier research has shown the Covid-19 hyperinflammatory response to resemble secondary hemophagocytic lymphohistiocytosis (HLH), which is a rare and often fatal hyperinflammatory response triggered by autoimmune disorders, certain cancers, and infections.

Kaser wrote that while secondary HLH remains poorly understood, Mendelian-inherited primary HLH points toward CD8+ T lymphocytes, natural killer cells and dendritic cells triggering a cytokine storm involving macrophages.

Other shared features between secondary HLH and severe Covid-19 are cytopenia, hyperferritinemia, disseminated intravascular coagulation, acute respiratory distress syndrome, multiple organ dysfunction, excessive expansion of T lymphocytes, and bone marrow histiocytic hyperplasia with hemophagocytosis with aggregates of interstitial CD8+ lymphocytes, he noted.

The Severe Covid-19 GWAS Group concluded that further exploration of the (study) findings both as to their usefulness in clinical risk profiling of patients with Covid-19 and toward a mechanistic understanding of the underlying pathophysiology, is warranted.

In his commentary, Kaser concluded that the clinical success of treating Covid-19 patients on mechanical ventilation with the corticosteroid dexamethasone provides strong evidence that death may be caused by a late hyperinflammatory phase.

A therapeutic agent that converts severe Covid-19 into a manageable, nonfatal infection would render this pandemic a lesser concern, he wrote.

Because it is impossible to predict mechanisms straight from genomic coordinates, experimental testing of the biology of implicated genetic risk pathways is a route, albeit a potentially challenging one, toward that goal.

Salynn Boyles, Contributing Writer, BreakingMED

Karlsen reported grants from Stein Erik Hagen (via Canica A/S) during the conduct of the study; personal fees from Gilead Sciences, personal fees from Novartis, personal fees from Engitix, and personal fees from Intercept outside the submitted work.

Kaser had no disclosures.

Cat ID: 497

Topic ID: 495,497,282,497,125,190,926,192,927,151,59,928,925,934

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Genetic Variants Linked to Severe Covid-19 - Physician's Weekly

African cattle breeds are astonishingly diverse, and often quite beautiful. They range from the dark-red Ankole of southern Uganda, with their massive heat-dissipating horns, to the Boran which thrive in the dusty plains of northern Kenya, to Ethiopias sturdy Mursi cattle, with their prominent shoulder humps and hanging dewlaps. The Kuri that graze on the grasses of Lake Chad are adept swimmers; the Red Fulani can trudge vast distances along the margins of the Sahara; and the famously disease-resistant Sheko inhabit tsetse fly-infested forests of southwest Ethiopia.

All billion or so cattle today descend from ancient aurochs, an extinct species of wild cattle that once inhabited large swaths of Eurasia. These cattle were domesticated on at least two distinct occasions approximately 10,000 years ago during the Neolithic era: once in south Asia leading to the zebu or humped cattle and the other in the Middle East leading to the taurine or humpless cattle.

In Africa, the oldest archaeological evidence of domestic cattle dates back to between 6000 and 5000 BC in western Egypt. These taurine cattle, initially confined to the Saharan-Sahelian belt, eventually reached isolated pockets of land in West and East Africa.

Africas cattle today have adapted to the climate, forage conditions, diseases and pests prevalent in their habitat. The individuals best adapted to their environments were more likely to survive and reproduce. They were also more favoured by people. Over time this led to different breeds and species.

Today there are an estimated 800 million livestock keepers across the continent. Cattle provide nutritious, calorie-dense food, much-needed income, and nitrogen-rich manure for replenishing soils. There are few regions of Africa where cattle do not play a central role, both economically and culturally.

But it was not always this way. My colleagues and I from the International Livestock Research Institute (ILRI) recently published a paper detailing how African cattle acquired their adaptive capacities.

Sifting through the DNA of 16 indigenous African breeds, we discovered a thousand-year-old event in which the worlds two main subspecies of cattle namely taurine and zebus mixed. This allowed African cattle after spending thousands of years confined to certain regions in Africa to diversify and spread across the continent.

Our findings help to explain how African cattle spread throughout the continent. But since they were selected and bred for resilience, African cattle never became as productive, in terms of meat or milk, as breeds in more temperate climates. Our hope is that, by studying the history hidden in indigenous cattle genomes, we can help guide efforts to breed for productivity without losing the breeds native resilience and sustainability.

Our new genome sequencing work revealed that, about a thousand years ago, pastoralist herders in the Horn of Africa began breeding the Asian zebu cattle with local taurine breeds.

The zebu offered traits that allowed cattle to survive in hot, dry climates. The taurine traits provided cattle with the ability to endure humid climates, where vector-borne diseases that affect cattle, like trypanosomiasis (or sleeping sickness) are common.

This event, which we dubbed an evolutionary jolt, allowed African cattle after spending thousands of years confined to a shifting patchwork of sub-regions in Africa to spread across the continent and flourish into the breeds we see today.

But this resilience came at a cost. African cattle are often not as productive in terms of growth rates, meat or milk as their European and American cousins. Canadian Holsteins, for example, can deliver 30 litres of milk per day, several times what most African breeds are capable of. Traditional Ethiopian Boran, for example, produced only four to six litres of milk per day.

Today scientists at ILRI, in partnership with governmental institutions in Tanzania and Ethiopia, are again trying to deliver an evolutionary jolt to Africas cattle. This time, however, they want to speed up the evolutionary clock by identifying genetic markers that signal both adaptability and productivity. Screening embryos for these markers could help scientists replicate in the lab the slow work of evolution by favouring the traits that most benefit farmers.

Earlier efforts to improve cattle productivity on the continent focused on importing cattle breeds from elsewhere, without adequately recognising African breeds unique resilience. Nearly, all these attempts have failed or resulted in crossbreeds with both adaptability and productivity diluted.

This time, we are focusing on sustainable productivityproductivity that builds on rather than disregards the resilience of indigenous African breeds.

But while we have new tools and shortcuts which enables scientists to analyse vast swaths of genetic data and decide which breeds could work well together, there are some lessons we should still draw from the first evolutionary jolt.

The first is that we shouldnt be overly concerned about crossbreeding. Because of a sense of national pride and wanting to conserve indigenous African cattle breeds, there is at times a tendency on the part of some to treat them as iconic, untouchable manuscripts.

This ignores the long tradition of crossbreeding practised by African livestock farmers and pastoralists they were (and still are) constantly mixing and matching breeds to select the animals best suited to their needs.

Another lesson is that, as scientists experiment and cross-breed, it is vitally important to remember that the local breeds have adaptations not all of them immediately obvious (a tolerance for episodic drought, for example) that have enabled their success. It is important that we do not lose those adaptive traits in the randomness of crossbreeding.

This will take innovative crossbreeding programs that incorporate scientists, government ministries, private partners and farmers to ensure the conservation of genetic information across the long life cycle of cattle generations.

And finally, its essential to include the practical, accumulated experience of pastoralists in these processes.

David Aronson, Senior Communications Advisor with ILRI, contributed to the writing of this article

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An evolutionary jolt helped cattle to spread across Africa. Now genetics must make them more productive - The Conversation Africa

The El Dorado Rotary Club hosted Tammy McKamie, a genetic certified nurse at the Christus St. Michael Health System in Texarkana, on Monday at their regular meeting, where she spoke about the health benefits of genetic testing.

McKamie, who has worked as a medical professional for nearly 40 years, is the only credentialed genetic certified nurse in Texas, and also serves patients from Arkansas. On Monday, she discussed her specialization in genetics and the role ones genes may play in determining whether they develop cancer during their lives.

While 90% of those who develop cancer do so because of environmental and lifestyle factors, such as smoking or being exposed to carcinogenic chemicals, McKamie said some people are at a heightened risk due to genetic factors.

Almost every person is born with 23 pairs of chromosomes, half of which are inherited from their biological mother and the other half of which are inherited from their biological father.

On each one of these chromosomes, there are thousands of genes. If I add up all the genes in this DNA, were going to have about 20,000 genes, and each one of those has a purpose, McKamie said.

Some of those genes purposes are to protect the individual from developing cancer, she said, a medical breakthrough that was discovered in 1994 during research for the Human Genome Project.

God gave us genes to protect us from cancer, McKamie said. We have two of each gene that theyve discovered so far. One gene may protect you from multiple cancers, so if ones defective, you may be at risk for multiple cancers.

Rotarian Art Noyes asked whether genetic predisposition to cancer may have been related to actress Angelina Jolies decision to undergo a double mastectomy (breast removal) several years ago.

Yes, Angelinas mother had ovarian cancer, so she had this genetic testing years ago, McKamie said. She did the genetic testing and she had a genetic mutation in one of these genes. Angelina had never had cancer, but she had the genetic predisposition toward it.

In Jolies case, McKamie said, there was likely a mutation of the BRCA 1 or 2 gene, which can heighten ones susceptibility to several types of cancers, including breast cancer, ovarian cancer, prostate cancer, colorectal cancer and other types.

For those who opt not to undergo preventative surgeries, like Jolies mastectomy, knowing of any genetic defects can still help medical professionals that care for them, since they will be aware of their increased risk level. Those who do have a genetic predisposition to some types of cancer should undergo earlier and more frequent screenings so that any cancer that does develop can be treated sooner, McKamie said.

If you started out with this defect, we would not wait til 40 (years old) to do a mammogram we would start much earlier, she said. Everybody knows that if you detect cancer early, youre more likely to survive it.

McKamie said a defect in the BRCA 1 or 2 gene can heighten a womans risk of developing breast cancer significantly. For someone without a gene defect, the risk at 40 years old is about 0.5%; at 50 years old, about 2%; and at 70 years old, about 7%. For a woman who does carry a hereditary risk, the likelihood that they will develop breast cancer by age 40 increases to 10 to 20%, depending on which BRCA gene the defect is in; by age 50, the risk is 33 to 50%, and by 70 the risk is 58-87%, McKamie said. For men, the risk of breast cancer increases from 1% for the general population to 7% for those with a genetic defect.

People take it for granted that everythings working but if you knew that one of these was defective and you were at a higher risk for cancer, you might be more healthy, more conscious, McKamie said.

At Christus St. Michael, McKamie offers consultations for those who would like to undergo genetic testing to determine whether they might be at a heightened risk for developing cancer. First, she will take a detailed family medical history and explain to her patient how ones genes might increase their risk for cancer. Following that, she will draw one tube of blood from the patient and send it to a laboratory, with a typical turnaround time of two to three weeks, she said.

This testing is now even evolved to the point to where if you have cancer, the physicians will use it to determine the best type of drug to use to treat you, McKamie said. I get a lot of consults from our cancer physicians and oncologists because they need to know what type of drug to use to treat this person.

McKamie noted that Medicare pays 100% for this sort of genetic testing, and most other medical insurance companies follow their lead; additionally, should any out-of-pocket costs emerge once a patients sample reaches the testing lab, a representative from the lab will call the patient to ensure they still want the testing done.

Before a patient comes to Texarkana for a screening, McKamie will screen them over the phone to ensure they will qualify for coverage for the genetic testing, she said. Those who are interested in a consult can contact her at 903-614-2654 or [emailprotected]

[Cancer diagnostics and treatment] just really evolved, and it continues to evolve, McKamie said. This is the way of the future now.

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Nurse advises Rotary of the benefits of genetic testing - El Dorado News-Times

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The 23andMe Genetic Kit Is an Insanely Cool Gift You May Just Want to Give Yourself - It's on Sale For Prime Day! - Yahoo News

Germline genetic testing is essential in order to identify optimal treatments for patients with cancer, as well as detecting inherited mutations via cascade testing that could affect family members, according to John M.Carethers, MD, MACP, who emphasized that improvements to genetic testing technology and testing costs has increased not only the accuracy of, but access to these assays.

The technology in sequencing has moved from the old gels to capillary to ChIP [chromatin immunoprecipitation]-based, and has revolutionized the way we approached it. The depth of [genetic testing] coverage [has evolved], said Carethers. Sequencing technologies totally revolutionized this [process].

He added, There are some unusual situations in which additional technologies have to be used to figure out some of the ones that typical ChIP technologies don't fully explain. That has markedly changed the way we approach [testing] these days.

In an interview withOncLiveduring the 2020 Institutional Perspectives in Cancer (IPC) webinar on Precision Medicine, Carethers, a professor of Internal Medicine and Human Genetics at the University of Michigan, discussed recent developments in multi-gene panel testing.

OncLive: How are predictive and somatic genetic tests being utilized in clinical practice?

Carethers: In terms of germline testing, the benefit is knowing which disease you carry, and that information can also spread to other family members to understand whether they [are at an increased risk of getting a cancer diagnosis]. Sometimes, at least in my experience, [germline testing] does alleviate some anxiety. Some people get more anxious once they know they have a germline mutation, but in general, it does at least explain the reason why they're seeing certain diseases in the family. Thats the general benefit for germline testing.

The benefit of somatic testing is knowing the type of mutations that occur in the tumor; there may be a therapeutic drug or compound that is in current use that could benefit the patient. For instance, I had a patient with unresectable esophageal cancer. She was dying and her esophagus was almost completely obstructed with the tumor. She had a feeding tube put into her stomach and lost a lot of weight; she was literally counting out the days until she died. With some thought, we decided to take a sample of the tumor and do somatic testing.

She had some mutations that werent typically found in esophageal cancer, and we did have drugs [to treat her]. She was actually put on those drugs and the tumor shrunk dramatically to the point that she could eat again, she gained weight, and she lived another 5 years. Normally, she wouldn't have lasted more than a few months. The benefits of somatic testing is understanding the genetic makeup of the tumor in which you might be able to use some compounds that exist to benefit the patient. Thats the real goal of somatic testing.

There is an unusual situation for somatic testing, as well. For instance, in colon cancer, we know about Lynch syndrome, but there is also a Lynch-like syndrome. In Lynch-like syndrome, there is no germline [mutation], but the tumor has 2 somatic mutations of a mismatch repair deficient tumor. They can look like a Lynch syndrome tumor, and maybe even behave a little bit like a Lynch syndrome tumor, but they're really not caused by a germline mutation. Sometimes, somatic genetics can help us understand tumor genesis as well as ways to treat the tumor.

What changes have we seen recently in multigene panel testing? How are test results interpreted and how do they help guide treatment strategies?

There are patients who will walk in with the classic phenotype and then there are patients walking in who don't have the classic phenotype, yet they carry that mutation in the same gene. Multigene testing allows us to account for phenotypic variation.

Someone may walk in with colon cancer, the next person in the family might walk in with endometrial cancer, and the next person in the family may walk in with a skin tumor, but they all line up with the same mutation in Lynch syndrome. However, if you saw the skin tumor first, would you have thought of Lynch [syndrome]? [What about] if you saw the endometrium or the colon cancer? It depends on the specialty and the type of disease presentation they show up with. In many cases, though, the disease could be subtle.

For instance, there was a family I followed, which comprised the grandmother, mother, and daughter. The grandmother, who was well into her late 60s, had a Lynch syndrome mutation and got her colon removed appropriately. The mother was in her 40s with no cancers, but the daughter who was 21, developed colon cancer. It looked like it skipped a generation, yet, they all carry the same mutation. There's phenotypic variation, even with this exact same mutation in the family, because we're all genetically different to some, so there's probably modifiers and other things going on. However, if I can see that in this one family who I know [harbor that specific] mutation [then I know that] if multiple people walk into the clinic and have variations in their family histories and in their personal history of cancer, that we are seeing a wide phenotypic variation.

Now, instead of testing 1 gene at a time, we will test 30 or 50 genes at a time, and you can pick up some of these less penetrant genes that are causing the phenotypic variation. Sometimes there are major penetrant genes in these families.

What other barriers to germline testing need to be addressed?

We're always learning. Every year or so we add a few more genes to our repertoire and then, maybe they get on some of these panels. E3 ubiquitin ligase WWP1 is associated with PTEN hamartomatumorsyndrome, which is not on any panels, but the paper was published in the New England Journal of Medicine. We keep learning as we discover more and more of these genes. The more genes that we find tend to occur in less and less people, based on our current knowledge, but some of these patients present with these rare phenomena.

We're also finding out that some of these mutations arent specifically a change in the DNA sequencethere are methylation, or rearrangement, or even a deletion. You have to use other techniques in addition to sequencing to figure those families out or those families will be left in the lurch.

The downside of doing multigene panel testing is that now, if you push for more whole-exome and whole-genome sequencing, we have a lot more variants. One commercial lab got [results] back to me 2 months ago from a patient we had tested 4 years ago. They said, We finally have enough people [where we could determine that] his variant is not significant. It was good news. We are now more sure of variants because they now have more families in their database at the commercial lab. Sometimes it takes years to figure it out, unless we have functional analysis for all variants. Thats a big challenge right now.

Where do you hope to see the future of genetic testing head?

In a good way, genetic testing will probably [have a lower] cost and there [will be an] ease of doing it [with] whole-exome and whole-genome sequencing. It will even overtake panel testing over time because the machines are better and faster. The key, though, is having a database that you can go back and forth and analyze. Youre going to need the analytics and tools. What happens with the patient? Do I carry this [information] on a flash drive? Is it in a database I have to have access to?

It's not an easy answer and I'm not sure if the health system that a particular patient goes to is going to store all this information3 billion base pairs of informationand go back to it each time. Each place is going to have to have the right analytic tools to go back and [retrieve that information]. There are going to be some challenges with that, even though that's the way the technology is going.

The more challenging pieces [are related to] direct-to-consumer (DTC) testing. You don't always know what you're getting on those tests. We can test you for common diseases, such as diabetes and hypertension, but we also test you for BRCA1/2. In reality, very few of the DTC [tests] are doing sequencing or panel testing like we do clinically. Many of them are using single nucleotide polymorphisms (SNPs) that give you a suggestion. Many of these start from ancestry companies,and they recently moved into [testing for] these diseases because people are interested. I don't blame them for doing this, but the information they give might only [include] a fraction of the actual disease variants. If someone finds an SNP in BRCA1/2 or Lynch syndrome, you might need to see a doctor. [Based on your family history or phenotype,] we may have to send a ChIP test to verify [the results].

In some cases, people will test just to be curious, and they think they're going to have something, but there is zero evidenceno personal history and no family history. There are going to be some challenges with the DTC [testing] because we don't always know the type of test theyre getting and the information is not going to be as precise and could present challenges in the clinics. Some people are going to get upset because we're going to say, No, you don't need testing, or [patients will ask], Why does this test say I might have it but your test says I don't? We have to explain all this and those are going to be challenges.

What else would you like to add regarding the evolution of genetic testing?

There is phenotypic variability in the presentation of many of these syndromes. The standard now is multigenetic panel testing to try to assuage the phenotypic variation; we do pick up [genes in] people who we didn't necessarily think had that disease. I've been surprised too many times, so I'm not surprised anymore. A lot of these inherited conditions have phenotypic variability. If you have any suspicion or your primary care physician has any suspicion, feel free to send [a test] to our clinic because we can investigate that and do testing that's relatively cheap if there's a good cause to investigate that. It may save their life and the lives of their loved ones.

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Focusing on the Future of Genetic Testing in Oncology - OncLive

The study has been launched in response to a recent escape of farm-raised salmon and will be managed by the wild-fish conservation body Fisheries Management Scotland, supported by scientists from Marine Scotland Science, and funded by Mowi Scotland.

The multi-year study of 115 sites aims to confirm wild salmons current genetic profile and to track for the potential of genetic changes should interbreeding of farmed and wild salmon occur.

In late August, Mowi Scotland confirmed that 48,834 farm-raised salmon escaped from its Carradale farm in the Firth of Clyde after it became detached from its seabed anchors during a combination of strong weather events.

Since the escape, Fisheries Management Scotland has been working with member District Salmon Fishery Boards and Fisheries Trusts, as well as angling associations, to monitor the situation and mitigate where possible. Escaped farmed salmon have been caught by anglers in multiple rivers across Loch Lomond, Ayrshire, Clyde, Argyll and in rivers in north-west England.

The priority for Fisheries Management Scotland and their members has been to ensure that any farmed fish are removed from the rivers, humanely dispatched, and scale samples submitted to enable accurate identification, and Mowi has committed to support these actions.

Dr Alan Wells, chief executive of Fisheries Management Scotland, said: We are very disappointed that this escape has occurred. The Carradale North farm is a new development, and we are all agreed it is not acceptable for such escapes to occur. It is crucial that lessons are learned, and that appropriate steps are taken to avoid such escapes happening in future.

We have welcomed Mowis commitment to work with us and to fund a comprehensive genetics study that will help us better understand the potential impacts. We will continue to engage with the industry and regulators, with a view to improving the situation for wild salmon and sea trout.

Ben Hadfield, COO of Mowi Scotland, said: I would like to thank Fisheries Management Scotland and their member District Salmon Fishery Boards and Fisheries Trusts for their efforts to remove these fish from rivers across the Firth of Clyde, and apologise for any disruption and concern this escape has caused all those with an interest in wild salmon. We have learned the root cause of the escape system anchor lines crossing and resulting in friction failure and acknowledge our responsibility to quickly learn from this event to prevent it from occurring again.

Polly Burns, aquaculture interactions manager at Fisheries Management Scotland, added: We would like to thank anglers for their continuing efforts to capture and report farmed fish entering our rivers. We have received about 150 reports of farmed fish captures from a range of rivers both within and out with the Firth of Clyde and we continue to urge anglers to report catches of farmed fish, using the reporting system on our website.

The Health and Welfare of Atlantic Salmon course

It is vital that fish farm operatives who are responsible for farmed fish are trained in their health andwelfare. This will help to ensure that fish are free from disease and suffering whilst at the same timepromote good productivity and comply with legislation.

This new and comprehensive study of genetic introgression aims to add to the understanding of one of the potential pressures on Scotlands wild salmon, which are approaching crisis-point. The Scottish Government has identified a range of high-level pressures on wild salmon to also include: over-exploitation, predation, invasive species, habitat loss and inshore commercial fisheries.

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Study will investigate the genetic impact of escaped farmed salmon - The Fish Site

Understanding genetic disease in mixed-breed and purebred dogs and cats can bring about more effective treatments and better client service, says clinical geneticist and general practitioner Dr. Jerold Bell.

If we understand the genetic background of our patients, were better positioned to prevent, to mitigate, or to alter the expression of genetic disease, allowing our patients to be healthier in their lifetimes as well as to breed healthier dogs and cats, Dr. Bell said.

An adjunct professor at the Cummings School of Veterinary Medicine at Tufts University, Dr. Bell spoke about genetic diseases during the AVMA Virtual Convention 2020 this August. In addition to his teaching duties, Dr. Bell works as a solo practitioner, and he sees dogs and cats all day long and sees genetic disease in our patients all day long.

He explained that common genetic disorders are caused by ancient disease liability genes that preceded breed formation. Since these mutations occurred long before the separation of breeds, these diseases are seen across all breeds and in mixed breeds.

The most common hereditary diseases in dogs are allergies, followed by hip and elbow dysplasia; inherited cancers such as lymphoma, hemangiosarcoma, mast cell tumor, and osteosarcoma; patella luxation; nonstruvite bladder stones; hypothyroidism; mitral valve disease; inflammatory bowel disease; diabetes mellitus; retained testicles; and umbilical hernias.

In cats, the most prevalent genetic diseases are inflammatory cystitis, then feline urological syndrome, diabetes mellitus, lymphoplasmocytic gingivostomatitis, nonstruvite bladder stones, allergies, eosinophilic skin disease, and inflammatory bowel disease.

Disease is not a function of homozygosity, which happens when identical DNA sequences for a particular gene are inherited from both biological parents, nor is it a consequence of inbreeding. Rather, Dr. Bell explained, hereditary diseases are a result of the accumulation and propagation of specific disease liability genes. Breed-related deleterious genes accumulate in various ways, including direct selection for disease-associated phenotypes, linkage to selected traits, carriage by popular sires, genetic drift, andmost importantlythe absence of selection against deleterious phenotypes.

If we dont select for healthy parents to produce offspring, then we have no expectation of health in those offspring, Dr. Bell said. Not selecting for health is selecting for disease, and we need to understand that and pass that on to our breeder clients.

On the topic of disease and extreme phenotypes, Dr. Bell said brachycephalic obstructive airway syndrome is frequently diagnosed at veterinary clinics on account of the popularity of certain brachycephalic dog breeds, namely Pugs, French Bulldogs, and Bulldogs. Most breed standards do not call for the expression of extreme phenotypes, he said, nor do they select for the most extreme size or the most extreme brachycephalic trait.

Moderation away from extremes that cause disease should be the guiding principle in breeding, Dr. Bell noted, and in judging dog shows.

Common genetic diseases seen in mixed-breed dogs and cats occur randomly because of dispersed ancient liability genes, according to Dr. Bell. Uncommon and breed-specific recessive or complexly inherited disease is far less likely to occur in mixed-breed individuals.

Dr. Bell said designer-bred dogs and cats often have inherited diseases common in random-bred populations. They can also inherit disease liability genes shared by the parent breeds or parent species. So if youre breeding short-statured breeds together, it wouldnt be surprising to see patellar luxation, or in smaller toy size breeds, to see mitral valve disease, he said.

Hereditary disease manifests as a result of anatomical mismatch between parent breeds. We see a lot of this in dental disease, where we see crowding of teeth and malocclusions and misplaced teeth, Dr. Bell continued. Even in the musculoskeletal, if you breed two breeds with different body types together, we may see degenerative joint disease and poor joints. All of these things, all need to be monitored.

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Making sense of genetic disease in dogs and cats - American Veterinary Medical Association

SAN DIEGO, Oct. 15, 2020 (GLOBE NEWSWIRE) -- Bionano Genomics, Inc. (Nasdaq: BNGO) announced that a study led by scientists and clinicians from the Institute for Human Genetics at the UCSF School of Medicine and the Department of Pediatrics at the University of Colorado School of Medicine and published in bioRxiv used Bionanos proprietary genome imaging technology to identify novel disease causing variants in patients with three different genetic diseases and in a diverse control dataset of 154 individuals. The study found that Bionano's Saphyr System was able to comprehensively analyze complex genome structures called segmental duplications and helped identify several novel structural variations associated with each disease causing locus increasing the understanding of these diseases.

Segmental duplications are large segments of repetitive sequences tens to hundreds of thousands of base pairs in size. Short-read and long-read sequencing technologies cannot span these large segments of the genome. Only Bionanos optical mapping technology can image single molecules that are so long that they span the segmental duplications. These repetitive sequences can interact with each other when sperm or eggs are created and their rearrangement can cause severe genetic disease. Some of the most common of such diseases are microdeletions at 7q11.23, also known as Williams-Beuren syndrome (WBS), 15q13.3 microdeletion syndrome, 16p12.2 microdeletion syndrome and 22q11.2 deletion syndrome, also known as DiGeorge syndrome.

This study, published in bioRxiv, provides a population-level analysis of segmental duplications in 154 people and in patients with WBS, 15q13.3, and 16p12.2 microdeletion syndromes. Several novel SVs were detected for each locus, and the exact disease causing rearrangement was determined with much higher accuracy than was formerly possible without Saphyr. As previously announced, a recent publication in the journal Nature published on July 22, 2020 also discussed the unique contribution of Bionanos optical mapping technology to understanding the genetic causes of DiGeorge syndrome.

Erik Holmlin, Ph.D., CEO of Bionano Genomics commented, The microdeletion and microduplication syndromes are common genetic disorders, yet the exact genomic structures that cause them have been difficult or impossible to characterize with current sequencing-based methods. Even though microdeletion syndromes are commonly represented by hallmark features, in many cases a wide variability in clinical features is observed. Being able to understand and measure the subtle structural differences in microdeletions among different patients could allow for better clinical or therapeutic management. An increasing number of studies have relied on Bionanos Saphyr system to characterize disease-causing structural variants that could not be correctly analyzed with other molecular techniques. We will continue to make our technology available to researchers everywhere who want to greatly expand the capabilities of their genomic analysis.

The publication is available at https://www.biorxiv.org/content/10.1101/2020.04.30.071449v1.full

About Bionano GenomicsBionano is a genome analysis company providing tools and services based on its Saphyr system to scientists and clinicians conducting genetic research and patient testing, and providing diagnostic testing for those with autism spectrum disorder (ASD) and other neurodevelopmental disabilities through its Lineagen business. Bionanos Saphyr system is a platform for ultra-sensitive and ultra-specific structural variation detection that enables researchers and clinicians to accelerate the search for new diagnostics and therapeutic targets and to streamline the study of changes in chromosomes, which is known as cytogenetics. The Saphyr system is comprised of an instrument, chip consumables, reagents and a suite of data analysis tools, and genome analysis services to provide access to data generated by the Saphyr system for researchers who prefer not to adopt the Saphyr system in their labs. Lineagen has been providing genetic testing services to families and their healthcare providers for over nine years and has performed over 65,000 tests for those with neurodevelopmental concerns. For more information, visitwww.bionanogenomics.com or http://www.lineagen.com.

Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as may, will, expect, plan, anticipate, estimate, intend and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) convey uncertainty of future events or outcomes and are intended to identify these forward-looking statements. Forward-looking statements include statements regarding our intentions, beliefs, projections, outlook, analyses or current expectations concerning, among other things: the contribution of Bionanos technology to the analysis or understandings of microdeletion syndromes and future development of better clinical or therapeutic management for such diseases; the effectiveness and utility of Bionanos technology in clinical settings; Saphyrs capabilities in comparison to other genome analysis technologies; the benefits of Bionanos optical mapping technology and its ability to facilitate genomic analysis in future studies; and Bionanos strategic plans. Each of these forward-looking statements involves risks and uncertainties. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include the risks and uncertainties associated with: the impact of the COVID-19 pandemic on our business and the global economy; general market conditions; changes in the competitive landscape and the introduction of competitive products; changes in our strategic and commercial plans; our ability to obtain sufficient financing to fund our strategic plans and commercialization efforts; the ability of medical and research institutions to obtain funding to support adoption or continued use of our technologies; the loss of key members of management and our commercial team; and the risks and uncertainties associated withour business and financial condition in general, including the risks and uncertainties described in our filings with the Securities and Exchange Commission, including, without limitation, our Annual Report on Form 10-K for the year ended December 31, 2019 and in other filings subsequently made by us with the Securities and Exchange Commission. All forward-looking statements contained in this press release speak only as of the date on which they were made and are based on management's assumptions and estimates as of such date. We do not undertake any obligation to publicly update any forward-looking statements, whether as a result of the receipt of new information, the occurrence of future events or otherwise.

CONTACTSCompany Contact:Erik Holmlin, CEOBionano Genomics, Inc.+1 (858) 888-7610eholmlin@bionanogenomics.com

Investor Relations Contact:Ashley R. RobinsonLifeSci Advisors, LLC+1 (617) 430-7577arr@lifesciadvisors.com

Media Contact:Darren Opland, PhDLifeSci Communications+1 (617) 733-7668darren@lifescicomms.com

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Bionano Genomics' Saphyr System Shown to be Indispensable for the Analysis of Certain Genetic Disease Causing Variants - GlobeNewswire

PITTSBURGH, Oct. 13, 2020 (GLOBE NEWSWIRE) -- NeuBase Therapeutics, Inc. (NASDAQ: NBSE) (NeuBase or the Company), a biotechnology company accelerating the genetic revolution using a new class of synthetic medicines, announced the addition of Peter Nielsen, Ph.D. to its scientific advisory board. Dr. Nielsen, the primary inventor of peptide nucleic acid (PNA) technology, brings extensive experience in genetic medicine to NeuBase as the Company optimizes its PATrOL therapies and moves them towards the clinic.

We are honored to welcome Dr. Nielsen, a transformational leader in the field of genetics and genomic technologies, to the NeuBase scientific advisory board. His unique perspective gained over his distinctive career will undoubtedly provide valuable insight and complement our team of renowned experts, said Dietrich A. Stephan, Ph.D., chief executive officer of NeuBase. We believe that our new class of synthetic medicines, which relies on the elegant scaffold chemistry invented by Dr. Nielsen, has the potential to change the treatment landscape for many diseases, both common and rare. We look forward to leveraging his unparalleled knowledge as we continue to advance our PATrOL platform under the guidance of our outstanding group of scientific advisors.

Dr. Nielsen added, NeuBases PNA technology is among the first to be advanced through development for therapeutic applications, and I am thrilled to be part of the revolution the Company is leading. I look forward to working with the team and lending my guidance as NeuBase progresses its first-in-class medicines.

Dr. Peter Nielsen is a leading expert in gene targeting, RNA interference and chemical replication and translation and was one of the inventors of PNAs in 1991. He is currently a professor at the University of Copenhagen where his lab focuses on PNAs in regard to drug discovery, gene targeting, antisense principles, cellular and in vivo delivery and administration of biopharmaceuticals. He is the co-author of more than 400 scientific papers and reviews as well as over 20 patents and patent applications, and he serves on the advisory board of four scientific journals.In addition to his esteemed academic career, Dr. Nielsen is the co-founder of two biotech companies in Denmark and is a member of EMBO and the Danish Academy of Technical Sciences. He received his Ph.D. in 1980 from University of Copenhagen.

About NeuBase Therapeutics, Inc.NeuBase is accelerating the genetic revolution using a new class of synthetic medicines. NeuBases designer PATrOL therapies are centered around its proprietary drug scaffold to address genetic diseases at the source by combining the highly targeted approach of traditional genetic therapies with the broad organ distribution capabilities of small molecules. With an initial focus on silencing disease-causing mutations in debilitating neurological, neuromuscular and oncologic disorders, NeuBase is committed to redefining medicine for the millions of patients with both common and rare conditions. To learn more, visit http://www.neubasetherapeutics.com.

Use of Forward-Looking Statements

This press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act. These forward-looking statements are distinguished by use of words such as "will," "would," "anticipate," "expect," "believe," "designed," "plan," or "intend," the negative of these terms, and similar references to future periods. These views involve risks and uncertainties that are difficult to predict and, accordingly, our actual results may differ materially from the results discussed in our forward-looking statements. Our forward-looking statements contained herein speak only as of the date of this press release. Factors or events that we cannot predict, including those risk factors contained in our filings with the U.S. Securities and Exchange Commission, may cause our actual results to differ from those expressed in forward-looking statements. The Company may not actually achieve the plans, carry out the intentions or meet the expectations or projections disclosed in the forward-looking statements, and you should not place undue reliance on these forward-looking statements. Because such statements deal with future events and are based on the Company's current expectations, they are subject to various risks and uncertainties, and actual results, performance or achievements of the Company could differ materially from those described in or implied by the statements in this press release, including: the Company's plans to develop and commercialize its product candidates; the timing of initiation of the Company's planned clinical trials; the timing of the availability of data from the Company's clinical trials; the timing of any planned investigational new drug application or new drug application; the Company's plans to research, develop and commercialize its current and future product candidates; the clinical utility, potential benefits and market acceptance of the Company's product candidates; the Company's commercialization, marketing and manufacturing capabilities and strategy; global health conditions, including the impact of COVID-19; the Company's ability to protect its intellectual property position; and the requirement for additional capital to continue to advance these product candidates, which may not be available on favorable terms or at all, as well as those risk factors contained in our filings with the U.S. Securities and Exchange Commission. Except as otherwise required by law, the Company disclaims any intention or obligation to update or revise any forward-looking statements, which speak only as of the date hereof, whether as a result of new information, future events or circumstances or otherwise.

NeuBase Investor Contact:Dan FerryManaging DirectorLifeSci Advisors, LLCDaniel@lifesciadvisors.comOP: (617) 430-7576

NeuBase Media Contact:Cait Williamson, Ph.D.LifeSci Communicationscait@lifescicomms.comOP: (646) 751-4366

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NeuBase Therapeutics Announces Addition of Peter Nielsen, Ph.D., Inventor of Peptide Nucleic Acid Technology, to Scientific Advisory Board - BioSpace

Researchers at the University of California, Davis, School of Veterinary Medicine have identified a genetic cause for the fatal condition equine familial isolated hypoparathyroidism (EFIH) in Thoroughbreds, marking the first genetic variant for hypoparathyroidism identified in any domestic animal species. Additionally, this is the first widely available genetic test for Thoroughbreds.

The study, led by Carrie Finno, DVM, PhD, Dipl. ACVIM, and Gary Magdesian, DVM, CVA, Dipl. ACVIM, ACVECC, ACVCP, wasreportedin the journalPLoS Genetics.Genetic testingcan now be performed at theUC Davis Veterinary Genetics Laboratoryto identify horses with the variant and avoid mating carriers that could produce affected foals.

For Thoroughbred owners and breeders, the loss of a foal has tremendous economic and emotional impacts, said first author Victor Rivas, who conducted the project as part of his undergraduate training in Finnos laboratory. It is important to promote safe and strategic breeding habits by actively breeding horses genetically screened not only for EFIH but for other diseases that may impact quality of life.

Foals affected with EFIH suffer from low blood calcium concentrations, resulting in involuntary muscle contractions, muscle stiffness that leads to a stiff gait and can progress to an inability to stand, seizures, fevers, and an abnormally fast pulse. Parathyroid hormone is typically produced to increase calcium levels in the body, but in these foals concentrations are low or inappropriately normal (i.e., they should be high due to the low calcium). Affected foals die or are euthanized due to poor prognosis. Necropsy results reveal underdeveloped or absent parathyroid glands.

Previously termed idiopathic hypocalcemia, EFIH has been observed in Thoroughbred foals up to 35 days of age. Disease onset and progression are likely determined by the amount of calcium in the diet early in life. This can vary based on dam milk calcium concentration and the amount of milk ingested.

In the current study, the researchers determined an autosomal recessive mode of inheritance and performed whole genome sequencing of two affected foals. A mutation in therap guanine nucleotide exchange factor 5(RAPGEF5) gene was present in two copies (homozygous) in both foals. They further analyzed the variant in a frog developmental model and demonstrated loss of function of the RAPGEF5 protein leading to aberrant development. Based on these data, the researchers hypothesize thatRAPGEF5might play a role in the derivation of the parathyroid gland during development.

Researchers have not identified the variant in individuals from 12 other breeds. The allele frequency for theRAPGEF5variant in an expanded set of 82 randomly selected, unaffected Thoroughbreds was 0.018. An unbiased allele frequency study has not been performed, so the allele frequency in the larger Thoroughbred population is currently unknown.

The next steps are to assess the allele frequency in a large population of randomly selected Thoroughbreds, said Finno. Additionally, we have discussed collaborating with Dr. Nathan Slovis at Hagyard Equine Medical Institute in Kentucky to test for the variant in cases of sudden death in Thoroughbred foals.

The clinical presentation of EFIH is similar to human familial hypoparathyroidism. Because theRAPGEF5gene is highly conserved across species, it is a potential new candidate gene for primary hypoparathyroidism in humans, the researchers said.

Excerpt from:
Genetic Variant for EFIH in Thoroughbreds Found The Horse - TheHorse.com

The revolution of genetic testing has led to more accurate and widespread assays for patients with cancer; however, as more genetic variants are identified, it has become a greater challenge to determine the optimal treatment for an individual patient, according to GouthamNarla, MD, PhD.

As we sequence more genes, we will have more information, which is a good thing, said Narla. Of course, we will also find more variants that, at this time, we don't know whether they're pathogenic or benign. They get lumped into the uncertain category, which creates uncertainty for patients and for providers, as well.

In an interview withOncLiveduring the 2020 Institutional Perspectives in Cancer (IPC) webinar on Precision Medicine, Narla, an associate professor in the Department of Medicine; chief of the Division of Genetic Medicine, Department of Medicine; and associate director of the Medical Scientist Training Program, University of Michigan, further discussed the utility of genomic testing and updates in next generation sequencing (NGS).

OncLive: Could you discuss the key advances in cancer genetics? What are some of the mechanisms that have driven its development?

Narla: A couple of major advancements we've seen in cancer genetics is the identification of additional disease-causing variants. It used to be when I first trained as a medical geneticist, we really only knew about BRCA1/2 and some of the mismatch repair genes. Now, we know about other genes, including PALB2, and other members and genes in that family. That has expanded the testing opportunities for our patients.

The other aspect that has been very exciting is now some of these gene variants are predictive of response to therapies. We have therapies that can be specifically used and work for patients who harbor some of these germline variants. That has really changed the way in which we have treated patients who carry these variants.

What are some of the recent developments in NGS?

Previously, we were doing single-gene testing, oftentimes by Sanger sequencing. Now, we can do large panels of genes depending upon the company and the panel; these comprise anywhere from 60 to 70 genesin some cases, several thousand genes. It has allowed us to collect vast amounts of sequencing information. Some of it will not be directly actionable now, but it still fuels research opportunities for us at major academic medical centers, and when more knowledge [is] gained, we go back to some of those sequencing results to see if, in fact, there was something that is now actionable based upon new knowledge.

How are we using this information to develop targeting strategies?

A lot of the approaches that we are using now may not involve the directly targeting the defective gene or protein, but they are leveraging knowledge about how that defective gene or protein causes activation of targetable pathways. For example, when it comes to BRCA1 loss, that creates a unique opportunity to use a PARP inhibitor in a synthetic lethal interaction, where those cells become highly dependent upon that enzyme. Then, you can inhibit with small molecules [or perhaps] approved PARP inhibitors, such as olaparib (Lynparza), and others for which there are now [a number of approved drugs that can target] a range of BRCA-deficient metastatic tumors.

How else has genomic testing evolved?

The evolution has been both in the number of individuals that we test, as well as how many genes we test. [For example, we used to] test families in which there are numbers of individuals who have cancer and we had a strong pretest probability that they would have a germline variant. Now, in fact, every patient with metastatic ovarian cancer, regardless of family history, gets tested. This is because we have PARP inhibitors for them. It not only has implications for their family but it also has implications for their treatment choices.

What guidelines have been helpful to your practice as it relates to genomic testing?

There are a number of organizations from the American Cancer Society to National Cancer Institute and the National Comprehensive Cancer Network (NCCN) that have very robust guidelines on who to test. There is also a little bit of subjectivity in making an appraisal with a genetics professional, meaning a genetic counselor or a medical geneticist, because not every family will fit the structure or will even know the entirety of their family history. There is some nuance to this, but there are definitely very established guidelines that exist and that we use when making these types of decisions.

However, the NCCN guidelines are very good and are used by [our institution. Then we apply our own nuances when we see the patient on a case by case basis. But, [in terms of] informing who should be tested and who should not, and which individual in the family should be [tested], the NCCN guidelines are a very good [resource].

What challenges could be addressed with future research?

I would like to see more of an effort to share data across all institutions and testing companies to reclassify these variants. I would like to see more basic science and translational science around what we call variant reclassification, so that we can really make definitive calls about the sequence changes that we see. The more genes we sequence, the more variants we find, and on larger panels, [we can see these uncertain variants in up to] 20% of patients. We're finding something in a gene, but we don't know whether it's good or bad for the patient.

Are there any new capabilities or technologies emerging that you find particularly exciting?

From a technology perspective, the last 10 years in sequencing has been a revolution; the cost of sequencing has come down and the accuracy has gone up. I'm not sure that we're going to see that much more of a revolution in the sequencing technology; it will be more efficient and more cost effective. We're [going to see] the identification of new genes associated with disease [and will therefore] it will be in the variant reclassification space.

What testing or sequencing studies are of particular interest?

One type of study that has read-out recently comprise the effectiveness of immunotherapy in patients who have mismatch repair deficient tumors. That has been really game-changing for those patients. The other major study is the use of PARP inhibitors in BRCA-mutant tumorsoriginally in the second- and third-line settings of ovarian cancer. [PARP inhibitors] have now moved to maintenance [therapy], pancreatic cancer, prostate cancer, and others. That has changed the management of patients with BRCA-positive tumors.

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Identifying Genetic Variants, Matching With Targeted Therapies Serve as Next Great Challenge With Germline Testing in Oncology - OncLive

Science's COVID-19 coverage is supported by the Pulitzer Center.

It's one of the pandemic's puzzles: Most people infected by SARS-CoV-2 never feel sick, whereas others develop serious symptoms or even end up in an intensive care unit clinging to life. Age and preexisting conditions, such as obesity, account for much of the disparity. But geneticists have raced to see whether a person's DNA also explains why some get hit hard by the coronavirus, and they have uncovered tantalizing leads.

Now, a U.K. group studying more than 2200 COVID-19 patients has pinned down common gene variants that are linked to the most severe cases of the disease, and that point to existing drugs that could be repurposed to help. It's really exciting. Each one provides a potential target for treatment, says genetic epidemiologist Priya Duggal of Johns Hopkins University.

Kenneth Baillie of the University of Edinburgh, an intensive care physician and geneticist, led the new study, which he discussed on 2 October at an online meeting of a data-pooling effort called the COVID-19 Host Genetics Initiative. He's hoping the results, also posted as a preprint on medRxiv, will speed treatments, although he cautions that any clinical trial inspired by the findings should wait for the study's acceptance in a peer-reviewed journal. Because the epidemic is progressing at such an alarming rate, even a few months of time saved will save lots of lives, Baillie says.

A study of some of the sickest COVID-19 patients, such as those placed on ventilators, has identified gene variants that put people at greater risk of severe disease.

In a standard approach to finding genes that influence a condition, geneticists scan the DNA of large numbers of people for millions of marker sequences, looking for associations between specific markers and cases of the disease. In June, one such genome-wide association study in The New England Journal of Medicine (NEJM) found two hits linked to respiratory failure in 1600 Italian and Spanish COVID-19 patients: a marker within the ABO gene, which determines a person's blood type, and a stretch of chromosome 3 that holds a half-dozen genes. Those two links have also emerged in other groups' data, including some from the DNA testing company 23andMe.

The new study confirmed the chromosome 3 region's involvement. And because 74% of its patients were so sick that they needed invasive ventilation, it had the statistical strength to reveal other markers, elsewhere in the genome, linked to severe COVID-19. One find is a gene called IFNAR2 that codes for a cell receptor for interferon, a powerful molecular messenger that rallies the immune defenses when a virus invades a cell. A variant of IFNAR2 found in one in four Europeans raised the risk of severe COVID-19 by 30%. Baillie says the IFNAR2 hit is entirely complementary to a finding reported in Science last month: Very rare mutations that disable IFNAR2 and seven other interferon genes may explain about 4% of severe COVID-19 cases (25 September, p. 155). Both studies raise hopes for ongoing trials of interferons as a COVID-19 treatment.

A more surprising hit from the U.K. study points to OAS genes, which code for proteins that activate an enzyme that breaks down viral RNA. A change in one of those genes might impair this activation, allowing the virus to flourish. The U.K. data suggest there is a variant as common and influential on COVID-19 as the interferon genetic risk factor.

Other genes identified by Baillie's team could ramp up the inflammatory responses to lung damage triggered by SARS-CoV-2, reactions that can be lethal to some patients. One, DPP9, codes for an enzyme known to be involved in lung disease; another, TYK2, encodes a signaling protein involved in inflammation. Drugs that target those two genes' proteins are already in useinhibitors of DPP9's enzyme for diabetes and baricitinib, which blocks TYK2's product, for arthritis. Baricitinib is in early clinical testing for COVID-19, and the new data could push it up the priority list, Baillie says.

The chromosome 3 region still stands out as the most powerful genetic actor: A single copy of the disease-associated variant more than doubles an infected person's odds of developing severe COVID-19. Evolutionary biologists reported last month in Nature that this suspicious region actually came from Neanderthals, through interbreeding with our species tens of thousands of years ago. It is now found in about 16% of Europeans and 50% of South Asians.

But the specific chromosome 3 gene or genes at play remain elusive. By analyzing gene activity data from normal lung tissue of people with and without the variant, the U.K. team homed in on CCR2, a gene that encodes a receptor for cytokine proteins that play a role in inflammation. But other data discussed at last week's meeting point to SLC6Z20, which codes for a protein that interacts with the main cell receptor used by SARS-CoV-2 to enter cells. I don't think anyone at this point has a clear understanding of what are the underlying genes for the chromosome 3 link, says Andrea Ganna of the University of Helsinki, who co-leads the COVID-19 Host Genetics Initiative.

The U.K. genetics study did not confirm that the ABO variants affect the odds of severe disease. Some studies looking directly at blood type, not genetic markers, have reported that type O blood protects against COVID-19, whereas A blood makes a person more vulnerable. It may be that blood type influences whether a person gets infected, but not how sick they get, says Stanford University geneticist Manuel Rivas. In any case, O blood offers at best modest protection. There are a lot of people with O blood that have died of the disease. It doesn't really help you, says geneticist Andre Franke of the Christian-Albrecht University of Kiel, a co-leader of the NEJM study.

Researchers expect to pin down more COVID-19 risk genesalready, after folding in the U.K. data plumbed by Baillie's team, the COVID-19 Host Genetics Initiative has found another hit, a gene called FOXP4 implicated in lung cancer. And in a new med-Rxiv preprint posted last week, the company Ancestry.com reports that a gene previously connected to the effects of the flu may also boost COVID-19 susceptibility only in men, who are more likely to die of the disease than women.

Geneticists have had little luck so far identifying gene variants that explain why COVID-19 has hit Black people in the United States and United Kingdom particularly hard. The chromosome 3 variant is absent in most people of African ancestry. Researchers suspect that socioeconomic factors and preexisting conditions may better explain the increased risks. But several projects, including Baillie's, are recruiting more people of non-European backgrounds to bolster their power to find COVID-19 gene links. And in an abstract for an online talk later this month at the American Society of Human Genetics annual meeting, the company Regeneron reports it has found a genome region that may raise the risk of severe disease mainly in people of African ancestry.

Even as more genetic risk factors are identified, their overall effect on infected people will be modest compared with other COVID-19 factors, Duggal says. But studies like the U.K. team's could help reveal the underlying biology of the disease and inspire better treatments. I don't think genetics will lead us out of this. I think genetics may give us new opportunities, Duggal says.

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Found: genes that sway the course of the coronavirus - Science

By Deborah Borfitz

October 15, 2020| The Bio-IT World Conference & Expo closed out with a plenary keynote presentation on preventive genomics by Robert Green, M.D., professor of medicine at Harvard Medical School and a physician-scientist who directs the G2P Research Program at Brigham and Womens Hospital and the Broad Institute. Data-sharing difficulties were a recurring theme at this years conference but, as the COVID-19 Host Genetics Initiative has demonstrated, it is possible to combine genomic data to rapidly explore markers of disease, he says. But far more daily deaths are caused by cancer and cardiovascular diseasenot the pandemic virusand 59 of the causal genes are already known and actionable.

Genomic information is rarely incorporated into clinical care partly because labs, not care providers, are doing most of the testing and doctors are unclear if the benefits outweigh the costs and risks, says Green. The clinical value of DNA sequencing is also unproven, although its the central feature of personalized medicine programs that have been popping up around the country.

Green presented lessons learned from the MedSeq, exploring the impacts of incorporating genomic sequencing into everyday medicine for people with and without a suspected genetic cardiac disease, and BabySeq, testing methods for integrating sequencing into the care of newborns. Both are randomized trials funded by the National Institutes of Health.

MedSeq involved primary care physicians taking comprehensive family histories on participants with or without the addition of one-page genomic reports and following their outcomes. Reports from preventive genomic testing focused on defined, disease-specific variants with the highest clinical actionability, says Green, as distinct from indication-based testing looking at a wider universe of variants known or suspected of being pathogenic.

Notably, Green says, neither doctors nor patients experienced test-related anxietyeven when a monogenetic risk variant was discovered. In 100 individuals, 20% were found to carry a dominant mutation for a monogenetic condition. In fact, among the top four genetic mutations, sequencing often discovered ongoing disease that the healthcare system had missed.

Participating doctors, after only six hours of training, did not make any errors in communicating the results, adds Green. Healthcare spending six months post-disclosure was higher but not extraordinarily more. Two years later, 22% had been reclassified (e.g., variant of uncertain significance now likely benign or likely pathogenic variant now pathogenic).

In the smaller BabySeq Project, 11% of participants were identified as having monogenetic disease risk, Green says. As with MedSeq, a substantial number with genetic mutations already had phenotypic evidence of disease previously missed by their healthcare providers.

BabySeq additionally revealed no difference in bonding or vulnerability, says Green. Catastrophic distress is not an obstacle [to sequencing], as has often been suggested. The falling cost of genomic sequencing and interpretation should further improve the benefit-to-cost ratio.

Exactly how often does sequencing reveal something important? Herere the stats from Green: 91% of the time for recessive mutations, 80% for atypical responses to medications, 15% for dominant mutation, and 50% for elevated polygenic risk specific to at least one condition such as diabetes or cancer.

Polarizing Topic

The Mass General Brigham Biobank, which looked for the 59 genes linked to disease, has identified such mutations in over 350 of the roughly 36,000 people it has sequenced. In 75% if those cases, the mutations were linked to either cardiovascular disease or cancer and the individuals had no idea they were carrying mutations, says Green.

A significant number did not even want to know of their risk, he adds. A similarly high number met National Comprehensive Cancer Center criteria for genetic testing but had never before been tested.

The Preventive Genomics Clinic at Brigham and Womens Hospital, staffed by genetics experts and counselors, offers individuals a menu of testing options (whole genome sequencing as well as smaller panels) and also gives patients the option of being seen via telemedicine. The heart-touching stories shared on its website include a man nudged by discovered mutations to finally get a colonoscopy, revealing two cancerous lesions that were subsequently extracted, and another with worsening heart disease who learned the underlying cause was Fabry diseasea rare but treatable condition.

Genomics is a notoriously polarizing subject, Green says. The challenge in convincing the skeptics is that genomics crosses multiple therapeutic domains and testing needs to be repeated over individuals lifetime.

The exceptionalism of genomics is sometimes misplaced, he later adds, referring to the disproportionate amount of fear about misuse of genetic information relative to psychological or infectious disease data. Its perfectly possible for large groups to share genomic data that is not identifiable. Its not full-proof, but its [technically] feasible.

Federal genetic privacy laws prevent genetics-based discrimination by employers and health insurers, Green says. In July, Florida became the first state in the nation to enact a DNA privacy law that also prohibits life, disability and long-term care insurance companies from using genetic tests for coverage purposes.

Editors Note: Even if you missed the start of the event, Bio-IT World Conference & Expo virtualis still live. Register nowfor on-demand presentations.

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Proving The Value Of Preventive Genomics - Bio-IT World

PHILADELPHIA, Oct. 13, 2020 (GLOBE NEWSWIRE) -- Passage Bio, Inc. (NASDAQ: PASG), a genetic medicines company focused on developing transformative therapies for rare, monogenic central nervous system disorders, today announced publication of data in a murine model of GM1 gangliosidosis (GM1) demonstrating that a single intracerebroventricular injection of an optimized adeno-associated virus (AAV) into the cerebral spinal fluid (CSF) resulted in significant expression of Beta-galactosidase (-gal) in the brain and peripheral tissues, and demonstrated dose-related reductions in neuronal lysosomal storage lesions, neurological impairment and improvement in survival. These data were published online ahead of print in the November issue of the peer-reviewed scientific journal Human Gene Therapy (HGT).

This study suggests that delivery of an AAV vector optimized to express b-gal directly into the CSF restored b-gal activity in the brain and, if further developed and tested in human clinical trials, may be effective in modifying and preventing the devastating effects of the genetic disease GM1, said James Wilson, M.D., Ph.D., director of the Gene Therapy Program at the University of Pennsylvania (Penn) and chief scientific advisor of Passage Bio. The AAV vector used in the study is the same as Passage Bios PBGM01 gene therapy, which is designed to deliver a functional human GLB1 gene into the brain and optimized to express -gal. These preclinical study data support the further development of PBGM01 as a potential therapy for patients suffering from GM1.

GM1 is a rare and often life-threatening monogenic lysosomal storage disease caused by mutations in the GLB1 gene, which encodes lysosomal acid -gal. Reduced -gal activity results in the accumulation of toxic levels of GM1 in neurons throughout the brain, causing rapidly progressing neurodegeneration. GM1 manifests as a continuum of disease and is most severe in the infantile form, which is characterized by onset in the first six months of life with hypotonia (reduced muscle tone), progressive CNS dysfunction, and rapid developmental regression. Life expectancy for infants with GM1 is two to four years, and infantile GM1 represents approximately 60 percent of the incidence of 0.5 to 1 in 100,000 live births. Currently, there are no approved disease-modifying therapies available.

Results of the PBGM01 preclinical study were reported in the paper titled, A single injection of an optimized AAV vector into cerebrospinal fluid corrects neurological disease in a murine model of GM1 gangliosidosis, by Christian Hinderer, M.D., Ph.D., and colleagues, including gene transfer pioneer Dr. Wilson, from the Gene therapy Program, Department of Medicine, University of Pennsylvania Perlman School of Medicine. The study in part was previously presented at the 22nd annual Meeting of the American Society for Cell and Gene Therapy (ASCGT) in 2019.

This research evaluated the impact of single intracerebroventricular administration of the human -gal containing AAV vector on -galactosidase enzyme activity in the murine brain and peripheral tissues, lysosomal storage lesions, neurological function (including neurological exams and gait analysis) and survival in mice lacking the -galactosidase gene. The mice received the single administration at age one month and were evaluated over 300 days. -gal activity was increased significantly in the cerebral spinal fluid and serum of the vector-treated mice compared to vehicle control-treated mice. Significant improvements in gait assessments as measured by stride length and hind paw print length and significant preservation of neurological function as measured by neurological exam scores were observed throughout the study period in the human -gal vector-treated mice. There were significant decreases in lysosomal storage lesions of vector-treated animals and by day 300 all animals that received the two highest doses were still alive, whereas none of the vehicle control-treated animals had survived.

Were excited about being able to soon advance PBGM01 into the clinic, and the potential promise it holds for patients with GM1, the majority of whom are infants and for whom there are no approved disease modifying treatments, said Bruce Goldsmith, Ph.D., president and chief executive officer of Passage Bio. Our plan is to administer PBGM01 through intra-cisterna magna delivery into the brain, which we believe may offer several benefits in terms of safety, efficiency and distribution compared to other approaches.

Passage Bio expects to initiate dosing of PBGM01 in a Phase 1/2 trial late in the fourth quarter of 2020 or early in the first quarter of 2021 and remains on track to report initial 30-day safety and biomarker data late in the first half of 2021.

This research was supported by a research, collaboration and license agreement with Passage Bio. HGT is the Official Journal of the European Society of Gene and Cell Therapy, British Society for Gene and Cell Therapy, French Society of Cell and Gene Therapy, German Society of Gene Therapy, and five other gene therapy societies. Click here to read the full-text article on the HGT website.

About PBGM01PBGM01 is an AAV-delivery gene therapy currently being developed for the treatment of infantile GM1, in which patients have mutations in the GLB1 gene causing little or no residual -gal enzyme activity and subsequent neurodegeneration. PBGM01 utilizes a next-generation AAVhu68 capsid administered through intra-cisterna magna (ICM) to deliver a functional GLB1 gene encoding -gal to the brain and peripheral tissues. By reducing the accumulation of GM1 gangliosides, PBGM01 has the potential to halt or prevent neuronal toxicity, thereby restoring developmental potential. In preclinical models, PBGM01 has demonstrated broad brain distribution and wide uptake of the -gal enzyme in both the central nervous system (CNS) and critical peripheral organs, suggesting potential treatment for both the CNS and peripheral manifestations of GM1. The Company has received Orphan Drug and Rare Pediatric Disease designation for PBGM01 for patients with GM1 and expects to initiate dosing of its Phase 1/2 trial late in the fourth quarter of 2020 or early in the first quarter of 2021 and remains on track to report initial 30-day safety and biomarker data late in the first half of 2021.

About Passage BioPassage Bio is a genetic medicines company focused on developing transformative therapies for rare, monogenic central nervous system disorders with limited or no approved treatment options. The company is based in Philadelphia, PA and has a research, collaboration and license agreement with the University of Pennsylvania and its Gene Therapy Program (GTP). The GTP conducts discovery and IND-enabling preclinical work and Passage Bio conducts all clinical development, regulatory strategy and commercialization activities under the agreement. The company has a development portfolio of six product candidates, with the option to license eleven more, with lead programs in GM1 gangliosidosis, frontotemporal dementia and Krabbe disease.

University of Pennsylvania (Penn)Financial DisclosureDr. Wilson is a Penn faculty member and also a scientific collaborator, consultant and co-founder of Passage Bio. As such, he holds an equity stake in the company, receives sponsored research funding from Passage Bio, and as an inventor of certain Penn intellectual property that is licensed to Passage Bio, he may receive additional financial benefits under the license in the future. He is an inventor of intellectual property covering the technology described in paper published in HGT that is licensed from Penn to Passage Bio, and he may receive financial benefits under this license in the future. Penn also holds equity and licensing interests in Passage Bio.

Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of, and made pursuant to the safe harbor provisions of, the Private Securities Litigation Reform Act of 1995, including, but not limited to: our expectations about timing and execution of anticipated milestones, including our planned IND submissions, initiation of clinical trials and the availability of clinical data from such trials; our expectations about our collaborators and partners ability to execute key initiatives; our expectations about manufacturing plans and strategies; our expectations about cash runway; and the ability of our lead product candidates to treat the underlying causes of their respective target monogenic CNS disorders. These forward-looking statements may be accompanied by such words as aim, anticipate, believe, could, estimate, expect, forecast, goal, intend, may, might, plan, potential, possible, will, would, and other words and terms of similar meaning. These statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements, including: our ability to develop and obtain regulatory approval for our product candidates; the timing and results of preclinical studies and clinical trials;; risks associated with clinical trials, including our ability to adequately manage clinical activities, unexpected concerns that may arise from additional data or analysis obtained during clinical trials, regulatory authorities may require additional information or further studies, or may fail to approve or may delay approval of our drug candidates; the occurrence of adverse safety events; the risk that positive results in a preclinical study or clinical trial may not be replicated in subsequent trials or success in early stage clinical trials may not be predictive of results in later stage clinical trials; failure to protect and enforce our intellectual property, and other proprietary rights; our dependence on collaborators and other third parties for the development and manufacture of product candidates and other aspects of our business, which are outside of our full control; risks associated with current and potential delays, work stoppages, or supply chain disruptions caused by the coronavirus pandemic; and the other risks and uncertainties that are described in the Risk Factors section in documents the company files from time to time with theSecurities and Exchange Commission(SEC), and other reports as filed with theSEC. Passage Bio undertakes no obligation to publicly update any forward-looking statement, whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise.

For further information, please contact:

Investors:Sarah McCabe and Zofia MitaStern Investor Relations, Inc.212-362-1200sarah.mccabe@sternir.comzofia.mita@sternir.com

Media:Gwen FisherPassage Bio215.407.1548gfisher@passagebio.com

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Passage Bio Announces Publication of Preclinical Data That Show Single Injection of Optimized AAV Vector into Cerebral Spinal Fluid - BioSpace

BALA CYNWYD, Pa., Oct. 13, 2020 (GLOBE NEWSWIRE) -- Larimar Therapeutics, Inc. (Nasdaq:LRMR), a clinical-stage biotechnology company focused on developing treatments for complex rare diseases,today announced the formation of its Scientific Advisory Board (SAB). Larimars SAB is comprised of distinguished research scientists, professors and industry experts recognized as key opinion leaders in the fields of rare disease, pediatrics and mitochondrial disease.

Larimar is privileged to have this group of prestigious, multidisciplinary advisors who are committed to advancing the research and development of CTI-1601 for Friedreichs ataxia, said Nancy M. Ruiz, MD, FACP, FIDSA, Chief Medical Officer of Larimar Therapeutics. Their scientific perspectives will be invaluable to determine our strategic scientific pathway and support the development of other potential treatments for complex rare diseases to help fill unmet medical needs in this space.

Formalizing the SAB adds to our recent accomplishments, which include resuming our Phase 1 clinical trial of CTI-1601 for Friedreichs ataxia and receiving a positive opinion on orphan drug designation for CTI-1601 from the European Medicines Agencys Committee for Orphan Medicinal Products, said Carole Ben-Maimon, MD, President and Chief Executive Officer of Larimar Therapeutics. This progress helps position Larimar for success as we continue to execute our strategy of developing treatments for complex rare diseases.

The members of Larimars SAB are as follows:

About Larimar TherapeuticsLarimar Therapeutics, Inc. (Nasdaq:LRMR), is a clinical-stage biotechnology company focused on developing treatments for complex rare diseases. The companys lead compound, CTI-1601, is currently being evaluated in a Phase 1 clinical program in the U.S. as a potential treatment for Friedreichs ataxia, a rare and progressive genetic disease. Larimar also plans to use its intracellular delivery platform to design other fusion proteins to target additional rare diseases characterized by deficiencies in intracellular bioactive compounds. For more information, please visit: https://larimartx.com.

Investor Contact:Joyce AllaireLifeSci Advisors, LLC(212) 915-2569jallaire@lifesciadvisors.com

Media Contact:Gina Cestari6 Degrees(917) 797-7904gcestari@6degreespr.com

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Larimar Therapeutics Announces Formation of Scientific Advisory Board - GlobeNewswire

COPENHAGEN, Denmark, Oct. 13, 2020 /PRNewswire/ -- Novo Seeds, the early stage investment and company creation team of Novo Holdings, today announced an investment in Rappta Therapeutics ("Rappta"), an emerging biotech company focused on developing first-in-class anti-cancer drugs activating protein phosphatase 2A (PP2A). The investment is a part of a EUR 9M series A financing round.

PP2A is a critical enzyme regulating protein de-phosphorylation and a key tumor suppressor which to date has been very difficult to target pharmaceutically. Rappta has developed proprietary tools and a unique understanding of PP2A which allows it to therapeutically reactivate PP2A. As a result of PP2A's central role in the regulation of protein de-phosphorylation, Rappta's PP2A-reactivating technologies offer the potential to develop multiple lead compounds and build a platform for a new class of anti-cancer drugs.

Rappta has assembled a strong scientific, management and commercial team based in Finland and the US. Rappta's scientific team, led by CSO and co-founder, Professor Goutham Narla, Division Chief of Genetic Medicine at the University of Michigan, represents world-leading expertise in PP2A. The scientific team has published seminal papers onthe structural, functional and biological mechanisms of PP2A inactivation in human cancer. The team will be supported by the Scientific Advisory Board lead by Dr. William Hahn, a Professor of Medicine at the Harvard Medical School and the Chief Scientific Officer at the Dana-Farber Cancer Institute.

As a resut of the financing, Jeroen Bakker, Principal at Novo Seeds will join the Board.Other investors in the Series A round include Novartis Venture Fund ("NVF"), Advent Life Sciences ("Advent") and one family office.

Jeroen Bakker, Principal, Novo Seeds, said: "We are impressed by the team's pioneering work in PP2A-reactivating technologies. Novo Seeds' strategy is to back teams from all over the globe with world class science and attract other bluechip investors to help transform these entreprises into successful business in the Nordics. We are very pleased to see renowned investors such as NVF and Advent investing in the region. We look forward to working with them as we support Rappta's world-leading team translate their scientific and medical expertise in phosphatase biology into a clinical oncology biotech."

Mikko Mannerkoski, CEO and co-founder of Rappta Therapeutics, commented: "We are very pleased to attract such a strong syndicate of international investors which validates our approach to developing novel therapies to target the previously undruggable target protein PP2A. This funding will enable us to accelerate the development of our platform and advance the lead compounds towards clinical development."

The investment in Rappta follows recent Novo Seeds participation in Galecto's Series D and Chromologics seed financing rounds.

About Rappta Therapeutics

Rappta Therapeutics, based in Finland and the US, is developing first-in-class anti-cancer drugs activating protein phosphatase 2A (PP2A). It has developed proprietary tools and a unique understanding of PP2A which allows it to therapeutically reactivate PP2A, a critical enzyme regulating protein de-phosphorylation and tumor growth, with the potential to create a new class of anti-cancer drugs. Rappta has a strong scientific, management and commercial team. Its scientific team, led by CSO and co-founder, Professor Goutham Narla, Head of Cancer Research at the University of Michigan, represent world-leading expertise in PP2A. It is backed by blue-chip investors Advent Life Sciences, Novartis Venture Fund, Novo Seeds and one family office. For more information, go to http://www.rappta-therapeutics.com.

About Novo Holdings A/S

Novo Holdings A/S is a private limited liability company wholly owned by the Novo Nordisk Foundation. It is the holding and investment company of the Novo Group, comprising Novo Nordisk A/S and Novozymes A/S, and is responsible for managing the Novo Nordisk Foundation's assets.

Novo Holdings is recognized as a leading international life science investor, with a focus on creating long-term value. As a life science investor, Novo Holdings provides seed and venture capital to development-stage companies and takes significant ownership positions in growth and well-established companies. Novo Holdings also manages a broad portfolio of diversified financial assets. Further information: http://www.novoholdings.dk

SOURCE Novo Holdings

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Novo Seeds co-leads Rappta Therapeutics Series A Financing for the Development of Phosphatase 2A drugs - PRNewswire

People with blood type O may be less vulnerable to COVID-19 and have a reduced likelihood of getting severely ill, according to two studies published Wednesday. Experts say more research is needed.The research provides further evidence that blood type (also known as blood group) may play a role in a person's susceptibility to infection and their chance of having a severe bout of the disease. The reasons for this link aren't clear and more research is needed to say what implications, if any, it has for patients.Studies add to growing evidenceA Danish study found that among 7,422 people who tested positive for COVID-19, only 38.4% were blood type O even though, among a group of 2.2 million people who were not tested, that blood type made up 41.7% of the population.By contrast, 44.4% of group A tested positive, while in the wider Danish population that blood type makes up 42.4%.In the other study, researchers in Canada found that among 95 patients critically ill with COVID-19, a higher proportion with blood type A or AB 84% required mechanical ventilation compared with patients with blood group O or B, which was 61%.The Canadian study also found those with blood type A or AB had a longer stay in the intensive care unit, a median of 13.5 days, compared with those with blood group O or B, who had a median of nine days."As a clinician ... it is at the back of my mind when I look at patients and stratify them. But in terms of a definitive marker we need repeated findings across many jurisdictions that show the same thing," said Dr. Mypinder Sekhon, an intensive care physician at Vancouver General Hospital and an author of the Canadian study."I don't think this supersedes other risk factors of severity like age and co-morbities and so forth," added Sekhon, who is also a clinical assistant professor in the Division of Critical Care Medicine and Department of Medicine at the University of British Columbia."If one is blood group A, you don't need to start panicking. And if you're blood group O, you're not free to go to the pubs and bars."No need to worryMost humans fall into one of four blood groups: A, B, AB or O. In the United States, the most common blood groups are O and A.It makes very little difference to most people's daily lives unless you have to have a blood transfusion. Nor should people worry unduly about the link between blood type and COVID-19, said Dr. Torben Barington, the senior author of the Danish paper and a clinical professor at Odense University Hospital and the University of Southern Denmark."We do not know whether this is some kind of protection of group O, or whether it's some kind of vulnerability in the other blood groups," he said."I think this has scientific interest, and when we find out what the mechanism is, perhaps we're able to use that proactively in some way in regard to treatment."In the Danish study, researchers analyzed data on Danish individuals who were tested between February 27 and July 30, and the distribution of blood types among those people was compared with data from people who had not been tested. They found that blood group wasn't a risk factor for hospitalization or death from COVID-19.Both studies were published in the journal Blood Advances.While there are several theories, researchers don't yet know what mechanism could explain the link between different blood groups and COVID-19.Sekhon said it could be explained by people with blood type O having less of a key clotting factor making them less prone to coagulation problems in the blood. Clotting has been a major driver of the severity of COVID-19.Other possible explanations involve blood group antigens and how they affect the production of infection fighting antibodies. Or it could be linked to genes associated with blood types and their effect on receptors in the immune system."It's a repeated, interesting scientific observation that really warrants further mechanistic work," he said.'Important research question'The findings of the two new studies provide "more converging evidence that blood type may play a role in a person's susceptibility to COVID infection and their chance of having a severe bout of COVID-19," said Dr. Amesh Adalja, senior scholar at the Johns Hopkins University Center for Health Security in Baltimore, who was not involved in either of the studies.A separate study, published in The New England Journal of Medicine in June, found genetic data in some COVID-19 patients and healthy people suggesting that those with Type A blood had a higher risk of becoming infected, and those with type O blood were at a lower risk.That previous genetic study, paired with the two new studies in Blood Advances, are "suggestive that this is a real phenomenon that we're seeing," said Adalja, whose work is focused on emerging infectious disease."While we're not quite to the point where this is ironclad, it's clearly suggestive, and we have not seen anything inconsistent with this. The same pattern has been emerging with O blood type tending to be the one that's standing out," Adalja said.Adalja said that blood types and their susceptibility to various infections have been studied in the medical literature before. For instance, research suggests that people with blood type O appear to be more susceptible to norovirus infection.As for the novel coronavirus that causes COVID-19, "We need to figure out the mechanism and understand it at the molecular level to be able to say for sure how this is occurring that this is really the O blood type and not something that kind of tracks with O blood type," Adalja said."We're starting to see enough now that I think it's an important research question to answer," he said. "There's more science to be done here, but it seems to me that there's more evidence accumulating for this hypothesis."

People with blood type O may be less vulnerable to COVID-19 and have a reduced likelihood of getting severely ill, according to two studies published Wednesday. Experts say more research is needed.

The research provides further evidence that blood type (also known as blood group) may play a role in a person's susceptibility to infection and their chance of having a severe bout of the disease. The reasons for this link aren't clear and more research is needed to say what implications, if any, it has for patients.

A Danish study found that among 7,422 people who tested positive for COVID-19, only 38.4% were blood type O even though, among a group of 2.2 million people who were not tested, that blood type made up 41.7% of the population.

By contrast, 44.4% of group A tested positive, while in the wider Danish population that blood type makes up 42.4%.

In the other study, researchers in Canada found that among 95 patients critically ill with COVID-19, a higher proportion with blood type A or AB 84% required mechanical ventilation compared with patients with blood group O or B, which was 61%.

The Canadian study also found those with blood type A or AB had a longer stay in the intensive care unit, a median of 13.5 days, compared with those with blood group O or B, who had a median of nine days.

"As a clinician ... it is at the back of my mind when I look at patients and stratify them. But in terms of a definitive marker we need repeated findings across many jurisdictions that show the same thing," said Dr. Mypinder Sekhon, an intensive care physician at Vancouver General Hospital and an author of the Canadian study.

"I don't think this supersedes other risk factors of severity like age and co-morbities and so forth," added Sekhon, who is also a clinical assistant professor in the Division of Critical Care Medicine and Department of Medicine at the University of British Columbia.

"If one is blood group A, you don't need to start panicking. And if you're blood group O, you're not free to go to the pubs and bars."

Most humans fall into one of four blood groups: A, B, AB or O. In the United States, the most common blood groups are O and A.

It makes very little difference to most people's daily lives unless you have to have a blood transfusion. Nor should people worry unduly about the link between blood type and COVID-19, said Dr. Torben Barington, the senior author of the Danish paper and a clinical professor at Odense University Hospital and the University of Southern Denmark.

"We do not know whether this is some kind of protection of group O, or whether it's some kind of vulnerability in the other blood groups," he said.

"I think this has scientific interest, and when we find out what the mechanism is, perhaps we're able to use that proactively in some way in regard to treatment."

In the Danish study, researchers analyzed data on Danish individuals who were tested between February 27 and July 30, and the distribution of blood types among those people was compared with data from people who had not been tested. They found that blood group wasn't a risk factor for hospitalization or death from COVID-19.

Both studies were published in the journal Blood Advances.

While there are several theories, researchers don't yet know what mechanism could explain the link between different blood groups and COVID-19.

Sekhon said it could be explained by people with blood type O having less of a key clotting factor making them less prone to coagulation problems in the blood. Clotting has been a major driver of the severity of COVID-19.

Other possible explanations involve blood group antigens and how they affect the production of infection fighting antibodies. Or it could be linked to genes associated with blood types and their effect on receptors in the immune system.

"It's a repeated, interesting scientific observation that really warrants further mechanistic work," he said.

The findings of the two new studies provide "more converging evidence that blood type may play a role in a person's susceptibility to COVID infection and their chance of having a severe bout of COVID-19," said Dr. Amesh Adalja, senior scholar at the Johns Hopkins University Center for Health Security in Baltimore, who was not involved in either of the studies.

A separate study, published in The New England Journal of Medicine in June, found genetic data in some COVID-19 patients and healthy people suggesting that those with Type A blood had a higher risk of becoming infected, and those with type O blood were at a lower risk.

That previous genetic study, paired with the two new studies in Blood Advances, are "suggestive that this is a real phenomenon that we're seeing," said Adalja, whose work is focused on emerging infectious disease.

"While we're not quite to the point where this is ironclad, it's clearly suggestive, and we have not seen anything inconsistent with this. The same pattern has been emerging with O blood type tending to be the one that's standing out," Adalja said.

Adalja said that blood types and their susceptibility to various infections have been studied in the medical literature before. For instance, research suggests that people with blood type O appear to be more susceptible to norovirus infection.

As for the novel coronavirus that causes COVID-19, "We need to figure out the mechanism and understand it at the molecular level to be able to say for sure how this is occurring that this is really the O blood type and not something that kind of tracks with O blood type," Adalja said.

"We're starting to see enough now that I think it's an important research question to answer," he said. "There's more science to be done here, but it seems to me that there's more evidence accumulating for this hypothesis."

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People with blood type O may have lower risk of COVID-19 infection and severe illness, studies suggest - WCVB Boston

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Phenylketonuria (PKU) is a congenital disease in which patients lack an enzyme that breaks down the amino acid Phenylalanine (Phe). Untreated, PKU leads to intellectual disability, seizures and movement disorders.

Today, babies are typically diagnosed with PKU 3-5 days after birth, from a heel prick blood test. And the primary treatment sounds simple avoid foods that contain Phe. But thats easier said than done.

One of the problems with PKU, even though newborn screening and control of diet of young kids is good, the diet is bland and not too interesting. When kids become teens we know they want to be able to go out and have a meal with friends and they struggle to keep symptoms in check, said Dr. Rob Nicholls, professor of pediatrics and director of the Birth Defects Laboratories at the University of Pittsburgh School of Medicine.

Since Phe is an amino acid, its present in any food that contains a lot of protein steak, fish, tofu, beans, etc. so people with PKU end up purchasing Phe-free food to get the protein they need to grow and stay healthy.

But, besides being bland, this special food can also be quite expensive. Families often need help paying for it, since its not covered by health insurance.

There are a few gene therapies in the pipeline, as well as a drug that works for some, as well as enzyme substitution therapy that involves frequent painful injections, Nicholls said, but most people still end up with a prescription for a special diet.

A major roadblock for developing better treatments is the lack of a good animal model for PKU research.

Genetically engineered laboratory rodents the workhorse of preclinical research dont display PKU symptoms, and researchers have yet to establish another animal that does the job.

A PKU pig and its unaffected littermate at 2 months of age.

So, Nicholls and colleagues developed a pig model of PKU, which they describe in a paper published today in JCI Insight.

According to study coauthor Dr. Jerry Vockley, chief of medical genetics at UPMC Childrens Hospital of Pittsburgh, who sees many PKU patients and their families each year in the clinic, this new pig model of PKU will allow for the advancement of better treatment options beyond a difficult-to-sustain diet.

Development of this model of PKU for the first time allows us the opportunity to develop improved therapies and test them in a meaningful way, opening the door to a better life for patients, Vockley said.

To create a pig model of PKU, the researchers crossed a Yucatan mini pig which grows to about the size of a small human with a domestic pig and used CRISPR gene editing to cut out part of the gene for phenylalanine hydroxylase (PAH), the enzyme that breaks down Phe.

The animals were born at the University of Missouri, in collaboration with Dr. Randall Prather, Director of the National Swine Resource and Research Center.

During infancy, the PKU model pig, who was born with two copies of the edited PAH gene, was much smaller than a littermate with only one copy of the edited gene. There were also clear brain differences.

Blood Phe levels were much higher in the PKU pig than either PKU patients off their diet or mice engineered to lack the PAH gene. A completely Phe-free diet brought the animals levels down to normal, only to spike again with a diet of 50% Phe-free chow.

To verify that the gene editing protocol didnt accidentally clip off any adjacent genes, lead author Dr. Erik Koppes, a postdoctoral fellow in Nichollss lab, sequenced the genome of the PKU pig and verified that the edited segment was within the bounds of the gene known to cause PKU.

Koppes also looked for off-target mutations across the genome a common concern with CRISPR but didnt find any.

It took quite a bit of genetic detective work, Nicholls said.

Next, Nicholls plans to begin breeding PKU pigs for future studies. He hopes to one day move the animals to a nearby farm, where the operation can scale up at a lower cost, with the ultimate goal of making the pig the preferred model of preclinical PKU research.

This research was funded by the National PKU Alliance (NPKUA) and an IGNITE grant from the National Institute of Neurological Disorders and Stroke.

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For PKU Research, Pigs Could Be the New Stand-In for People - UPMC

CAMBRIDGE, Mass. & SAN FRANCISCO--(BUSINESS WIRE)--Gemini Therapeutics, a clinical stage precision medicine company developing innovative treatments for genetically defined age-related macular degeneration (AMD), and FS Development Corp. (Nasdaq: FSDC), a special purpose acquisition company sponsored by Foresite Capital, today announced they have entered into a definitive merger agreement. Upon closing of the transaction, the company will be renamed Gemini Therapeutics, Inc. (Combined Company) and will be led by Jason Meyenburg, Chief Executive Officer of Gemini. The Combined Companys common stock is expected to be listed on Nasdaq.

In addition to the approximately $121 million held in FS Development Corp.s trust account (assuming no redemptions are effected), a group of premier healthcare investors has committed to participate in the transaction through a common stock PIPE of approximately $95 million at $10.00 per share. Investors in the PIPE include lead investor Foresite Capital, an affiliate of FS Development Corp.s sponsor, as well as Fidelity Management & Research Company LLC, Wellington Management, Boxer Capital of Tavistock Group, Alyeska Investment Group, L.P., Suvretta Capital Management, CVF, DAFNA Capital, and Acorn Bioventures, in addition to existing Gemini Therapeutics shareholders including Orbimed Healthcare Fund Management, Atlas Venture, Lightstone Ventures and Wu Capital.

This mornings announcement is important for the advancement of AMD research, as it ensures we have the necessary capital to advance our clinical programs and continue applying our insights in genetics and biology to pioneer first-in-class medicines to restore regulation of the complement system in the eye and throughout the body, bringing forward targeted precision therapies based on genetically defined populations, said Mr. Meyenburg. I would like to thank all those involved in making this transaction a success, particularly our new and existing blue chip investors, and the entire Gemini team.

Gemini embodies the type of company we had in mind when forming FSDC: a platform focused on the next generation of medicines utilizing genetics, said Jim Tananbaum, M.D., Chief Executive Officer of Foresite Capital and President and Chief Executive Officer of FS Development Corp. Gemini is developing treatments for patients losing their vision because of genetically driven macular degeneration. We are excited about the tremendous potential of this transaction, which we believe creates value for investors along with the potential to bring innovative new treatment options to patients.

Proceeds from the transaction are expected to provide Gemini with the capital needed to further develop its clinical programs and preclinical portfolio, including the following programs:

Post-closing of the transaction, Mr. Meyenburg and Dr. Tananbaum will be joined by board members from Gemini to form the seven-person board of directors.

Summary of Transaction

Current Gemini shareholders are converting 100% of their existing equity interests into common stock of the Combined Company. In addition to the approximately $121 million held in FSDCs trust account (assuming no redemptions are effected), an additional group of premier healthcare investors has committed to participate in the transaction through a common stock PIPE of approximately $95 million at $10 per share.

The Combined Company is expected to receive gross proceeds of approximately $216 million at the closing of the transaction (assuming no redemptions are effected), which is expected by January 2021. The close of this transaction is subject to approval of FSDCs shareholders and the satisfaction or waiver of certain other customary closing conditions.

Jefferies LLC and SVB Leerink acted as co-lead private placement agents for FS Development Corp. Jefferies LLC also acted as lead financial and capital markets advisor to FS Development Corp. Goldman Sachs & Co. LLC acted as lead financial advisor to Gemini in the transaction. Stifel acted as additional capital markets advisor to Gemini. Goodwin Procter LLP acted as legal counsel to Gemini. White & Case LLP acted as legal counsel to FS Development Corp.

The description of the business combination contained herein is only a high-level summary. Additional information about the transaction will be provided in a Current Report on Form 8-K that will contain an investor presentation to be filed by FS Development Corp. with the Securities and Exchange Commission (SEC) and will be available at http://www.sec.gov. In addition, FS Development Corp. intends to file a registration statement on Form S-4 with the SEC, which will include a proxy statement/prospectus, and will file other documents regarding the proposed transaction with the SEC.

In connection with the proposed business combination, FS Development Corp. intends to file a Registration Statement on Form S-4, including a preliminary proxy statement/prospectus and a definitive proxy statement/prospectus with the SEC. FS Development Corp.s stockholders and other interested persons are advised to read, when available, the preliminary proxy statement/prospectus and the amendments thereto and the definitive proxy statement/prospectus and documents incorporated by reference therein filed in connection with the proposed business combination, as these materials will contain important information about Gemini, FS Development Corp., and the proposed merger. When available, the definitive proxy statement/prospectus and other relevant materials for the proposed merger will be mailed to stockholders of FS Development Corp. as of a record date to be established for voting on the proposed business combination. Stockholders will also be able to obtain copies of the preliminary proxy statement/prospectus, the definitive proxy statement/prospectus, and other documents filed with the SEC that will be incorporated by reference therein, without charge, once available, at the SECs website at http://www.sec.gov, or by directing a request to press@foresitecapital.com.

Conference Call Information

Gemini and FS Development Corp. will host a conference call today, Thursday, October 15, 2020, at 10:30 a.m. Eastern Time, to discuss the proposed transaction. To access the conference call, please dial (888) 317-6003 (local) or (412) 317-6061 (international) at least 10 minutes prior to the start time and reference conference ID: 4983831.

About Gemini Therapeutics

Gemini Therapeutics is a clinical stage precision medicine company developing innovative treatments for age-related macular degeneration (AMD) by developing drugging strategies that are matched to specific genetic mutations found in patients with high clinical unmet need. Geminis lead clinical stage candidate, GEM103, is a recombinant form of the naturally occurring complement factor H protein currently in a Phase 2a trial in dry AMD patients with a complement factor H mutation. The company has generated a rich pipeline including recombinant proteins, gene therapies, and monoclonal antibodies. Geminis CLARITY natural history study is designed to provide unprecedented insight into the role of genetic risk in common retinal diseases and began in December 2018. Gemini was launched with funding from leading life science investors and powered by academic partnerships globally.

For more information, visit http://www.geminitherapeutics.com.

About FS Development Corp. (FSDC)

FS Development Corp., sponsored by Foresite Capital, is a blank check company formed for the purpose of effecting a business combination with one or more businesses in the biotechnology sector. The company is led by Jim Tananbaum, M.D., the CEO of Foresite Capital, an investment firm funding visionary healthcare entrepreneurs with approximately $3 billion in assets under management. The firm is headquartered in San Francisco.

Important Information About the Merger and Where to Find It

A full description of the terms of the business combination will be provided in a registration statement on Form S-4 to be filed with the SEC by FS Development Corp. that will include a prospectus with respect to the Combined Companys securities to be issued in connection with the business combination and a proxy statement with respect to the shareholder meeting of FS Development Corp. to vote on the business combination. FS Development Corp. urges its investors, shareholders and other interested persons to read, when available, the preliminary proxy statement/ prospectus as well as other documents filed with the SEC because these documents will contain important information about FS Development Corp., Gemini and the business combination. After the registration statement is declared effective, the definitive proxy statement/prospectus to be included in the registration statement will be mailed to shareholders of FS Development Corp. as of a record date to be established for voting on the proposed business combination. Once available, shareholders will also be able to obtain a copy of the S-4, including the proxy statement/prospectus, and other documents filed with the SEC without charge, by directing a request to: FS Development Corp., Attn: Secretary, 600 Montgomery Street, Suite 4500, San Francisco, California 94111. The preliminary and definitive proxy statement/prospectus to be included in the registration statement, once available, can also be obtained, without charge, at the SECs website (www.sec.gov).

Participants in the Solicitation

FS Development Corp. and Gemini Therapeutics and their respective directors and executive officers may be considered participants in the solicitation of proxies with respect to the proposed business combination described in this press release under the rules of the SEC. Information about the directors and executive officers of FS Development Corp. is set forth in FS Development Corp.s final prospectus filed with the SEC pursuant to Rule 424(b) of the Securities Act of 1933, as amended (the Securities Act) on August 13, 2020, and is available free of charge at the SECs website at http://www.sec.gov or by directing a request to: FS Development Corp., Attn: Secretary, 600 Montgomery Street, Suite 4500, San Francisco, California 94111. Information regarding the persons who may, under the rules of the SEC, be deemed participants in the solicitation of the FS Development Corp. shareholders in connection with the proposed business combination will be set forth in the registration statement containing the proxy statement/prospectus for the proposed business combination when it is filed with the SEC. These documents can be obtained free of charge from the sources indicated above.

Forward-Looking Statements

This press release contains forward-looking statements that are based on beliefs and assumptions and on information currently available. In some cases, you can identify forward-looking statements by the following words: may, will, could, would, should, expect, intend, plan, anticipate, believe, estimate, predict, project, potential, continue, ongoing or the negative of these terms or other comparable terminology, although not all forward-looking statements contain these words. These statements involve risks, uncertainties and other factors that may cause actual results, levels of activity, performance or achievements to be materially different from the information expressed or implied by these forward-looking statements. Although we believe that we have a reasonable basis for each forward-looking statement contained in this press release, we caution you that these statements are based on a combination of facts and factors currently known by us and our projections of the future, about which we cannot be certain. Forward-looking statements in this press release include, but are not limited to, statements regarding the proposed business combination, including the timing and structure of the business combination, the proceeds of the business combination, the initial market capitalization of the Combined Company and the benefits of the business combination, as well as statements about the potential attributes and benefits of Geminis product candidates and the format and timing of Geminis product development activities and clinical trials. We cannot assure you that the forward-looking statements in this press release will prove to be accurate. These forward-looking statements are subject to a number of significant risks and uncertainties that could cause actual results to differ materially from expected results, including, among others, the ability to complete the business combination due to the failure to obtain approval from FS Development Corp.s shareholders or satisfy other closing conditions in the Merger Agreement, the occurrence of any event that could give rise to the termination of the Merger Agreement, the ability to recognize the anticipated benefits of the business combination, the outcome of any legal proceedings that may be instituted against FS Development Corp. or Gemini following announcement of the proposed business combination and related transactions, the impact of COVID-19 on Geminis business and/or the ability of the parties to complete the business combination, the ability to obtain or maintain the listing of FS Development Corp.s common stock on Nasdaq following the proposed business combination, costs related to the proposed business combination, changes in applicable laws or regulations, the possibility that FS Development Corp. or Gemini may be adversely affected by other economic, business, and/or competitive factors, and other risks and uncertainties, including those to be included under the header Risk Factors in the registration statement on Form S-4 to be filed by FS Development Corp. with the SEC and those included under the header Risk Factors in the final prospectus of FS Development Corp. related to its initial public offering. Most of these factors are outside of FS Development Corp.s and Geminis control and are difficult to predict. Furthermore, if the forward-looking statements prove to be inaccurate, the inaccuracy may be material. In light of the significant uncertainties in these forward-looking statements, you should not regard these statements as a representation or warranty by us or any other person that we will achieve our objectives and plans in any specified time frame, or at all. The forward-looking statements in this press release represent our views as of the date of this press release. We anticipate that subsequent events and developments will cause our views to change. However, while we may elect to update these forward-looking statements at some point in the future, we have no current intention of doing so except to the extent required by applicable law. You should, therefore, not rely on these forward-looking statements as representing our views as of any date subsequent to the date of this press release.

Non-Solicitation

This press release is not a proxy statement or solicitation of a proxy, consent or authorization with respect to any securities or in respect of the proposed business combination and shall not constitute an offer to sell or a solicitation of an offer to buy any securities nor shall there be any sale of securities in any state or jurisdiction in which such offer, solicitation, or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction. No offer of securities shall be made except by means of a prospectus meeting the requirements of the Securities Act.

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Gemini Therapeutics and FS Development Corp. Announce Merger Agreement Creating Publicly Listed Precision Medicine Company Focused on Age-Related...

A new study by University of California researchers shows the promise of high-throughput DNA-sequencing technologies to improve prenatal diagnosis and pregnancy outcomes for women who have experienced an abnormal prenatal ultrasound.

In the UC San Francisco-led study, scientists used a technique called exome sequencing to identify genetic diseases as the underlying cause in 37 of 127 cases of nonimmune hydrops fetalis (NIHF), a life-threatening condition in which the fetus is overloaded with fluid. The study was published online Oct. 7 in The New England Journal of Medicine (NEJM).

Corresponding author Teresa Sparks, MD, MAS, a UCSF assistant professor in the Department of Obstetrics, Gynecology & Reproductive Sciences, led the study with senior study author Mary Norton, MD, a professor in the same department. The cause of most cases of NIHF is not identified with standard testing, but when we apply exome sequencing, we find a genetic diagnosis in nearly 30 percent of cases of previously unknown cause, Sparks said.

NIHF affects about one in every 1,700 to 3,000 pregnancies in the United States and is associated with high risks of stillbirth, preterm birth, neonatal death and other complications. Although NIHF often leads to death, identifying the precise genetic cause is critical, as associated outcomes vary widely in severity.

NIHF can be a manifestation of many genetic diseases, but evidence of abnormal fluid accumulation in the fetus detected through an ultrasound exam whether it occurs under the skin, in the abdomen, or around the heart or lungs does not pinpoint an underlying cause.

Participants in the study were referred from throughout the United States after NIHF was identified with prenatal ultrasound but no underlying genetic disease was found using long established methods for detecting genetic abnormalities. These traditional genetic tests karyotype and chromosomal microarray analysis detect large abnormalities in chromosomes, not disorders caused by a defect in a single gene as are identified with exome sequencing.

Exome sequencing is the complete spelling out of the genetic code for DNA segments within the genome that serves as the blueprints for proteins. This has become possible to perform quickly and accurately in recent years, thanks to the continual refinement of technology that can sequence DNA strands that are thousands of nucleotide building blocks long, often in a massively parallel manner that helps ensure accurate results. Exome sequencing can identify even the smallest mutations, such as a change in a single building-block nucleotide base pair.

Importantly, many of the disorders identified in the study have not previously been reported in association with NIHF, so the findings broaden knowledge of genetic diseases that can present with the condition. Among the most common of 37 genetic disorders identified in the NEJM study were 11 cases affecting a key intracellular signaling pathway called RAS-MAPK, four cases of inborn errors of metabolism, four cases of musculoskeletal disorders, and three cases each of lymphatic, neurodevelopmental, cardiovascular and blood disorders. Many of these diagnoses would also have been missed by commercial gene panels, Sparks said.

Most mutations identified in the study newly arose in the fetus, but several were inherited, with the potential to affect future pregnancies with the same biologic mother or father.

There is a very wide range in genetic diagnoses underlying NIHF, and identifying the diagnosis is essential for families and healthcare providers, Sparks said. With advanced genetic testing, there is much more we can discover for families to help them understand the situation, for obstetricians and neonatologists to better take care of the pregnancy and anticipate the needs of the newborn, and ultimately to guide the development of novel prenatal management strategies such as in-utero therapies to improve health outcomes over the long term.

For some of the genetic disorders identified in the study, prenatal interventions that can improve or save lives already have been identified. For example, genetic causes of anemia in the fetus may be closely monitored, and the fetus may receive a blood transfusion if needed.

Similarly, for some of the inborn errors of metabolism identified in the study, enzyme therapies already are available after birth. Early diagnosis and treatment of these metabolic disorders leads to better outcomes. A co-author of the NEJM study, Tippi MacKenzie, MD, a professor with the UCSF Department of Surgery, is investigating in utero treatments for specific genetic disorders underlying NIHF in a new clinical trial. Sparks, Norton, and co-authors are also pursuing further investigations to identify additional genomic abnormalities underlying NIHF for the cases that remain unsolved.

Co-Authors: All co-authors of the NEJM study are affiliated with the University of California FetalMaternal Consortium or the UCSF Center for Maternal-Fetal Precision Medicine. Additional UCSF co-authors of the study include Billie Lianoglou, Sarah Downum, Sachi Patel, Amanda Faubel, Anne Slavotinek, Patrick Devine, Ugur Hodoglugil, Jessica Van Ziffle, and Stephan Sanders.

Funding: The study was funded by the UCSF Center for Maternal-Fetal Precision Medicine, the Fetal Health Foundation, the Brianna Marie Foundation, Ultragenyx, and the National Institutes of Health.

The University of California, San Francisco (UCSF) is exclusively focused on the health sciences and is dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care.UCSF Health, which serves as UCSFs primary academic medical center, includes top-ranked specialty hospitals and other clinical programs, and has affiliations throughout the Bay Area.

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DNA Test Identifies Genetic Causes of Severe Fetal and Newborn Illness - UCSF News Services