Category Archives: Transhuman News

Researchers have identified 57 genetic variations of a gene strongly associated with declines in blood oxygen levels during sleep. Low oxygen levels during sleep are a clinical indicator of the severity of sleep apnea. The study, published today in the American Journal of Human Genetics, was funded by the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health.

A persons average blood oxygen levels during sleep are hereditary, and relatively easy to measure, says study author Susan Redline, MD, senior physician in the Division of Sleep and Circadian Disorders at Brigham and Womens Hospital, and professor at Harvard Medical School, in a release. Studying the genetic basis of this trait can help explain why some people are more susceptible to sleep disordered breathing and its related morbidities.

When we sleep, the oxygen level in our blood drops, due to interruptions in breathing. Lung and sleep disorders tend to decrease those levels further, and dangerously so. But the range of those levels during sleep varies widely between individuals and, researchers suspect, is greatly influenced by genetics.

Despite the key role blood oxygen levels play in health outcomes, the influence of genetics on their variability remains understudied. The current findings contribute to a better understanding, particularly because researchers looked at overnight measurements of oxygen levels. Those provide more variability than daytime levels due to the stresses associated with disordered breathing occurring during sleep.

The researchers analyzed whole genome sequence data from the NHLBIs Trans-Omics for Precision Medicine (TOPMed) program. To strengthen the data, they incorporated results of family-based linkage analysis, a method for mapping genes that carry hereditary traits to their location in the genome. The method uses data from families with several members affected by a particular disorder.

This study highlights the advantage of using family data in searching for rare variants, which is often missed in genome-wide association studies, says James Kiley, PhD, director of the Division of Lung Diseases at NHLBI. It showed that, when guided by family linkage data, whole genome sequence analysis can identify rare variants that signal disease risks, even with a small sample. In this case, the initial discovery was done with fewer than 500 samples.

The newly identified 57 variants of the DLC1 gene were clearly associated with the fluctuation in oxygen levels during sleep. In fact, they explained almost 1% of the variability in the oxygen levels in European Americans, which is relatively high for complex genetic phenotypes, or traits, that are influenced by myriad variants.

Notably, 51 of the 57 genetic variants influence and regulate human lung fibroblast cells, a type of cell producing scar tissue in the lungs, says study author Xiaofeng Zhu, PhD, professor at the Case Western Reserve University School of Medicine. This is important, he said, because Mendelian Randomization analysis, a statistical approach for testing causal relationship between an exposure and an outcome, shows a potential causal relationship between how the DLC1 gene modifies fibroblasts cells and the changes in oxygen levels during sleep.

This relationship, Kiley added, suggests that a shared molecular pathway, or a common mechanism, may be influencing a persons susceptibility to the lack of oxygen caused by sleep disordered breathing and other lung illnesses such as emphysema.

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Genetic Study: Shared Molecular Pathway Might Influence Susceptibility to Lack of Oxygen Caused by Sleep-disordered Breathing and Other Lung Illnesses...

CAMBRIDGE, Mass., Oct. 29, 2019 /PRNewswire/ -- Disc Medicine, a hematology company applying new insights in hepcidin biology to develop therapies that restore red blood cell production in hematologic diseases, today announced the completion of a $50 million Series A financing. The company's novel approach focuses on targeting hepcidin, a key regulator of iron metabolism, as a treatment for inherited and acquired anemias. The Series A financing was led by Novo Holdings A/S along with Access Biotechnology and founding investor Atlas Venture. Atlas seeded the company in 2017. Donald Nicholson, former CEO of Nimbus Therapeutics, is joining as the company's executive chairman.

"We have accumulated a wealth of experience and new insights into hepcidin biology and its role in hematologic diseases," said Brian MacDonald, founder and interim CEO of Disc Medicine. "We are harnessing these insights to develop first-in-class therapies targeting the hepcidin pathway to address a wide range of anemias."

Hepcidin is a small peptide hormone produced in the liver which acts as a key regulator of systemic iron metabolism. Dysregulation of hepcidin leads to either iron overload or iron deficiency, and chronic hepcidin dysregulation is observed in conditions associated with ineffective erythropoiesis, a state of impaired red blood cell production. Ineffective erythropoiesis disorders such as myelodysplastic syndromes, thalassemia, and anemia of chronic disease are often characterized by severe anemia that can have a significant impact on lifespan and quality of life.

Disc Medicine is advancing two therapeutic programs focused on regulating hepcidin expression - a novel, orally administered matriptase-2 inhibitor which increases hepcidin expression to treat iron loading anemias, and a hemojuvelin antagonist monoclonal antibody to reduce hepcidin expression and address anemia in a range of chronic inflammatory and hematologic diseases.

"Disc Medicine is poised to transform the treatment of these hematologic diseases with its novel approach to targeting hepcidin biology," said Kevin Bitterman, founding investor, Atlas Venture. "Over the past fifty years, the treatment of anemia has relied largely on blood transfusions which can be burdensome and even impair patient outcomes. Further, options are limited for patients who do not receive transfusions. With the launch of Disc Medicine, we seek to change the treatment paradigm with a new way to address the ineffective erythropoiesis that is associated with these diseases."

"We are pleased to support the Disc Medicine team in developing novel drugs to modulate the hepcidin axis to address multiple hematological diseases," said Nilesh Kumar, Partner, Novo Ventures. "The linearity of the science and the progress made by the team on targets backed by human genetics is an exciting development in this space."

Disc Medicine was founded in 2017 by Atlas Venture and Brian MacDonald. The Board of Directors is chaired by Donald Nicholson and includes Kevin Bitterman, Nilesh Kumar and Liam Ratcliffe. The Disc team is supported by world class medical advisors including Stefano Rivella, PhD, Professor of Pediatrics at The Children's Hospital of Philadelphia, Mark Fleming, MD, DPhil, Pathologist-in-Chief at Boston Children's Hospital and S. Burt Wolbach Professor of Pathology at Harvard Medical School, Srdan Verstovsek, MD, PhD, professor, Department of Leukemia at The University of Texas MD Anderson Cancer Center and Uma Sinha, PhD, chief scientific officer at BridgeBio Pharmaceuticals.

About Disc Medicine Disc Medicine is a hematology company harnessing new insights in hepcidin biology to address ineffective red blood cell production (erythropoiesis) in hematologic diseases. Focused on the hepcidin pathway, the master regulator of iron metabolism, Disc is advancing first-in-class therapies to transform the treatment of hematologic diseases. For more information, visit http://www.discmedicine.com.

About Atlas Venture Atlas Venture is a leading biotech venture capital firm. With the goal of doing well by doing good, the company has been building breakthrough biotech startups since 1993. Atlas works side by side with exceptional scientists and entrepreneurs to translate high impact science into medicines for patients. Our seed-led venture creation strategy rigorously selects and focuses investment on the most compelling opportunities to build scalable businesses and realize value. For more information, please visit http://www.atlasventure.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. For more information, visit http://www.novoholdings.dk.

About Access Biotechnology Access Biotechnology is the life science investment arm of Access Industries. The investment strategy is broad, long term and aims to enable truly innovative therapeutic platforms and products across three key stages: company foundation, technology translation and company expansion. Our approach is based on rigorous diligence and we provide value-added support from our extensive experience and networks.

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SOURCE Disc Medicine

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Disc Medicine Completes $50 Million Series A Financing led by Novo Holdings A/S to Advance New Therapies Addressing Ineffective Red Blood Cell...

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Newswise What began as a 51-year-old mystery comes down to a single gene, as researchers from the University of Chicago and University of California, San Francisco discovered the cause of a new inherited form of pancreatitis.

Pancreatitis is a disease that causes the pancreas to become inflamed, triggering severe abdominal pain. Long-term pancreatitis can cause the organ to stop functioning altogether, leading to diabetes, and in many cases, pancreatic cancer. It is most often caused by alcohol abuse, but several forms are caused by genetic mutations.

In 2012,Mark Anderson, who earned his MD and PhD at UChicago and is now an endocrinologist at UCSF, saw a patient in his clinic with diabetes and pancreatitis. She explained that it ran in her family in fact, they had been written up in a study for theAnnals of Internal Medicinein 1968. Doctors at UCSF had documented 71 members of the family, then living in a farming community around Northern California. Of the 18 people they examined, six were officially diagnosed with pancreatitis and another five were suspected of having the disease. The particular form of pancreatitis affecting this family was especially severe and struck at a young age; children suffering from it were said to come inside from the fields and collapse onto the floor in pain.

At the time, the researchers suspected that it was an autosomal dominant form of the disease, meaning that it could be inherited through one mutated gene. There was no way of proving this back then before the advent of genetic sequencing so the case was closed.

After Anderson and his colleagues realized the implications of their current patient's connections to that story, they ordered genetic tests for her and several of her family members. Working together withScott Oakes, MD, a former UCSF pathologist and cell biologist now on the faculty at UChicago, they screened the family for the five known genetic mutations that can cause inherited pancreatitis. None of them matched, but a new mutation in a gene that produces a digestive enzyme called elastase 3B emerged as a possible culprit.

In the lab, the researchers expressed both the normal and mutated forms of the elastase 3B gene, and used CRISPR gene-editing technology to engineer mice that had the mutation. They saw that the mutated form of the gene causes the pancreas to secrete too much of the enzyme, which damages the pancreas as it begins to digest itself. After 51 years, they had an answer for what was causing the unfortunate familys misery.

The tools to do genetic sleuthing now are just unbelievable, Anderson said. What an exciting time to be a clinician and a scientist. You really can take things from the bedside to the bench and back this quickly.

'Medical archaeology'

The discovery was published in September in theJournal of Clinical Investigation. Oakes, who calls it a work of medical archaeology, says its also an opportunity to find new treatments for inherited forms of pancreatitis, a notoriously difficult disease to treat. Short of removing the pancreas which has the equally problematic side effect of making the patient diabetic or performing a pancreas or islet cell transplant, doctors can mostly just help patients manage their pain and symptoms.

There are a lot of patients who still have what looks like inherited pancreatitis that don't have a genetic diagnosis maybe some of these have mutations in elastase 3B, Oakes said. So, it has immediate implications not only for this family but potentially other families that have pancreatitis.

Understanding how this mutation works could lead to solutions for more patients as well, Oakes said. New drugs could target the elastase 3B gene with an antibody or molecule that counteracts the extra enzymes.

The presentation is so dramatic its possible that elastase 3B might be a good place to intervene in regular, garden-variety pancreatitis, he said. If you could tamp it down, maybe you could help control the disease in other patients.

Oakes echoed Andersons sentiment about the advantage of working on such a problem at institutions like UChicago and UCSF, where physicians-scientists can see patients one day and work in a genetics lab the next.

This reinforces the advantage of seeing patients and running a lab: You can let human genetics drive our understanding of this disease, he said. There are a lot of families like this in the medical literature where we still don't know the genetics. I think it is an exciting time now to figure out how to do that.

The new study, Elastase 3B mutation links to familial pancreatitis with diabetes and pancreatic adenocarcinoma, was supported by the National Institutes of Health, the Helmsley Charitable Trust, the Bern Schwartz Family Foundation and the Larry L. Hillblom Foundation. Additional authors include Paul C. Moore, Jessica T. Cortez, Chester E. Chamberlain, Diana Alba, Amy C. Berger, Zoe Quandt, Alice Chan, Mickie H. Cheng, Jhoanne L. Bautista, Justin Peng and Michael S. German from UCSF.

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Gene discovery solves 51-year-old mystery cause of inherited pancreatitis - Newswise

NEW YORK Illumina officials were muted in their response to a threat from UK regulators that could potentially kill the firm's planned $1.2 billion acquisition of Pacific Biosciences. But that was just one of the storylines running through and around the firm's conference call following the release of its third quarter financial results.

"While we're still in the process of reviewing the documents, we continue to believe this acquisition is pro-competitive and in the best interests of customers and the genomics industry," Illumina CEO Francis deSouza said.

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Illumina Reserved in Comments on PacBio Deal, Forthcoming on Qiagen Deal and New Products - GenomeWeb

The Basics

A genome refers to an organism's complete set of DNA, including all of its genes. Therefore, WGS entails determining the complete DNA sequence at a point in time. It includes the organism's chromosomal DNA as well as DNA contained in the mitochondria.

While the field of genetics refers to the study of individual genes and their roles, genomics entails study of all of an organism's genes collectively- how they affect each other and the organism.

Simply put, the process of gene expression happens through synthesis of proteins. These proteins trigger the intended change in the cells and are synthesised after the corresponding DNA is transcripted to RNA in the cells nucleus.

Such DNAs which can be transcribed into messenger RNAs are called protein-coding DNA. Protein-coding DNA sequences are the most widely studied and best understood component of the human genome.

However, protein-coding DNA consist of only a small fraction of the genome - less than two per cent - the remaining 98 per cent of human genome consists of noncoding DNA.

Noncoding DNA that dont find a function in gene expression have biological functions- like regulating structural features of the chromosomes and DNA replication.

IndiGen is basically the India-specific version of the Human Genome Project (HGP), an an international scientific research project. The latter was primarily funded by the US government and was declared complete in 2003.

The HGP was able to map close to 92.1 per cent of the human genome, leaving out difficult portions of the chromosomes like centromeres and telomeres, with high accuracy.

Why genome sequencing is important

With the exception of identical twins, all humans show significant variation in genomic DNA sequences. People of same ethnicity/race may have more commonalities. Similarly. Based on genomic commonalities, certain populations of the world may be more susceptible to certain diseases, and so on.

Director General, CSIR and Secretary, Department for Scientific & Industrial Research, Dr Shekhar C Mande said that it is important to ensure that India, with its unparalleled human diversity, is adequately represented in terms of genomic data and develops indigenous capacity to generate, maintain, analyze, utilize and communicate large-scale genome data, in a scalable manner.

The broad-based genome data and knowhow for the its analysis will help in development of technologies for clinical and biomedical applications in India.

In the future, the technology is expected to deliver cost effective genetic tests, carrier screening applications for expectant couples, enabling efficient diagnosis of heritable cancers and pharmacogenetic tests to prevent adverse drug reactions.

On the occasion, the health minister also unveiled the IndiGenome card and accompanying IndiGen mobile application that enables participants and clinicians to access clinically actionable information in their genomes. This will pave the path for personalised treatments and precision medicine.

Genome sequencing also helps in evolutionary and anthropological studies. Genome sequencing has also helped us in developing better varieties of food crops.

However, the field also raises serious ethical, social concerns. The genome of a person can offer a host of information that is unknown to himself, to those who can analyse it. During the HGP, concerns were raised that the data might be used by big companies for hiring/firing employees, insurance companies to deny insurance to certain people etc. Therefore, privacy remains a serious concern.

The genomics has also revived the old debates over racial differences. Any genetic grounding of evolutionary differences between different races can have social repercussions with certain groups using the information to justify racial discrimination or race-purity.

Genomics also raise the ethical issues regarding human interference in natural processes. As the technology develops further, scientists would be able to design humans with assorted set of good genes.

Will this lead to a new form of Eugenics where parents discard a genetically inferior embryo early on? Will the rich be able to buy 'intelligence as they can buy beauty through lip injections, plastic surgeries, implants etc? What would the concepts like hard work, merit, equality etc mean in such a world?

These are some of the hard questions we will have to figure out as we move along.

Continued here:
Explained: Indias Own Human Genome Project, How It Will Aid Our Fight Against Cancer And Genetic Diseases - Swarajya

This article, written byRuanne Vent-Schmidt, University of British Columbia, originally appeared on The Conversation and has been republished here with permission:

Blind and partially sighted people no longer have to wait passively for a research breakthrough in hope of treatment options. In fact, people living with genetic eye conditions can now actively drive vision research forward by enrolling in a patient registry and getting their genes tested.

There are 2.2 billion people living with visual impairment globally. Some are living with inherited retinal diseases that are progressive and can lead to complete blindness. Up until recent years, blind and visually impaired people were told that no treatment is available. This is changing as genetic testing is paving the way for a surge of gene therapies.

My passion for vision research is personal

My doctoral dissertation at the University of British Columbia was on drug therapy for retinitis pigmentosa. This progressive, blinding eye condition is the most common type of inherited retinal disease.

In people affected by retinitis pigmentosa, the light sensing cells in their retina photoreceptors die early. Unlike skin cells that regenerate, the body does not make more photoreceptors once they are damaged.

As a vision scientist affected by retinitis pigmentosa, I am passionate about finding the truth about the disease. Why do photoreceptors die? How can we stop it? How can science and medicine help?

When I was 12 years old, I realized while at summer camp that my night vision was disappearing. In the last two decades, I lost my peripheral vision, contrast sensitivity and depth perception.

I worked in Dr. Orson Moritzs lab at the UBC department of ophthalmology and visual sciences, which focuses on research using tadpoles that contain known human mutations for retinitis pigmentosa to understand the disease.

I made an alarming discovery in our animal model: knowing the genetic cause of retinitis pigmentosa is vital for treatment with one class of drugs histone deacetylase inhibitors. These determine how genes are switched on or off.

A similar study in mice showed that the same drug reacted differently to variations in a single mutant gene that also causes retinitis pigmentosa.

Treating retinitis pigmentosa is like extinguishing fire. To stop a fire, you need to know whether its water-based or grease-based. If you try to use water to stop a grease fire, the damage gets worse.

Enrol in a patient registry

Blind and visually impaired people can advocate for eye health by enrolling in a patient registry. Participation in a registry benefits researchers by offering more information about the disease.

In Canada, individuals can self-refer to Fighting Blindness Canadas secure, clinical patient registry. This database is dedicated to connecting people living with retinal eye diseases to clinical trials and research.

When a gene therapy trial arises, researchers draw participants from this database. Since gene therapy aims to correct an underlying genetic mistake in DNA that causes disease, knowing the genetic cause of a disease is a criteria for most gene therapy trials.

Globally, other registries include My Retina Tracker in the United States, Target 5000 in Ireland, MyEyeSite in the United Kingdom, the Australian Inherited Retinal Disease Registry and Japan Eye Genetics Consortium. In New Zealand, Dr. Andrea Vincent has established the Genetic Eye Disease Investigation Unit. There is even a Blue Cone Monochromacy Patient Registry for one rare eye condition.

Blossoming gene therapy trials

In the last two decades, the number of gene therapy trials has blossomed. Currently, 250 genes on inherited retinal diseases have been identified. In 2017, the first gene therapy for inherited retinal disease Luxturna was approved by the United States Federal Drug Administration.

To date, there are trials for: retinitis pigmentosa; Usher syndrome, a condition that involves hearing and vision loss; achromatopsia, a disease that causes colour blindness; X-linked retinoschisis, a dystrophy that causes splitting of the retina and affects mostly in males; and age-related macular degeneration, the third-largest cause of vision loss worldwide, caused by the interplay between genetics and environment.

Enrolment in a patient registry and genetic testing advance the design of gene therapy trials. This in turn benefits blind and visually impaired people.

Research advancement is a concerted effort across the globe blind and partially sighted people should know they have the power to push it forward.

Ruanne Vent-Schmidt, PhD Candidate, Cell & Developmental Biology, University of British Columbia

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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BEYOND LOCAL: How people living with genetic eye conditions can drive vision research forward - GuelphToday