Category Archives: Genetic medicine

Drexel researchers have developed an algorithm toolkit that can identify communities of microbes in the human body and determine how they are functioning by finding patterns their genetic code.

An algorithm akin to the annoyingly helpful one that attempts to auto-complete text messages and emails is now being harnessed for a better cause. A group of Drexel University researchers are using its pattern-recognition ability to identify microbial communities in the body by sifting through volumes of genetic code. Their method could speed the development of medical treatments for microbiota-linked ailments like Crohns disease.

In the last decade, scientists have made tremendous progress in understanding that groups of bacteria and viruses that naturally coexist throughout the human body play an important role in some vital functions like digestion, metabolism and even fighting off diseases. But understanding just how they do it remains a question.

Researchers from Drexel are hoping to help answer that question through a clever combination of high-throughput genetic sequencing and natural language processing computer algorithms. Their research, which was recently published in the journal PLOS ONE, reports a new method of analyzing the codes found in RNA that can delineate human microbial communities and reveal how they operate.

Much of the research on the human microbial environment or microbiome has focused on identifying all of the different microbe species. And the nascent development of treatments for microbiota-linked maladies operates under the idea that imbalances or deviations in the microbiome are the source of health problems, such as indigestion or Crohns disease.

But to properly correct these imbalances its important for scientists to have a broader understanding of microbial communities as they exist both in the afflicted areas and throughout the entire body.

We are really just beginning to scrape the surface of understanding the health effects of microbiota, said Gail Rosen, PhD, an associate professor in Drexels College of Engineering, who was an author of the paper. In many ways scientists have jumped into this work without having a full picture of what these microbial communities look like, how prevalent they are and how their internal configuration affects their immediate environment within the human body.

Rosen heads Drexels Center for Biological Discovery from Big Data, a group of researchers that has been applying algorithms and machine learning to help decipher massive amounts of genetic sequencing information that has become available in the last handful of years. Their work and similar efforts around the world have moved microbiology and genetics research from the wet lab to the data center creating a computational approach to studying organism interactions and evolution, called metagenomics.

In this type of research, a scan of a genetic material sample DNA or RNA can be interpreted to reveal the organisms that are likely present. The method presented by Rosens group takes that one step farther by analyzing the genetic code to spot recurring patterns, an indication that certain groups of organisms microbes in this case are found together so frequently that its not a coincidence.

We call this method themetagenomics, because we are looking for recurring themes in microbiomes that are indicators of co-occurring groups of microbes, Rosen said. There are thousands of species of microbes living in the body, so if you think about all the permutations of groupings that could exist you can imagine what a daunting task it is to determine which of them are living in community with each other. Our method puts a pattern-spotting algorithm to work on the task, which saves a tremendous amount of time and eliminates some guesswork.

Current methods for studying microbiota, gut bacteria for example, take a sample from an area of the body and then look at the genetic material thats present. This process inherently lacks important context, according to the authors.

Its impossible to really understand what microbe communities are doing if we dont first understand the extent of the community and how frequently and where else they might be occurring in the body, said Steve Woloszynek, PhD, and MD trainee in Drexels College of Medicine and co-author of the paper. In other words, its hard to develop treatments to promote natural microbial coexistence if their natural state is not yet known.

Obtaining a full map of microbial communities, using themetagenomics, allows researchers to observe how they change over time both in healthy people and those suffering from diseases. And observing the difference between the two provides clues to the function of the community, as well as illuminating the configuration of microbe species that enables it.

Most metagenomics methods just tell you which microbes are abundant therefore likely important but they dont really tell you much about how each species is supporting other community members, Rosen said. With our method you get a picture of the configuration of the community for example, it may have E. coli and B. fragilis as the most abundant microbes and in pretty equal numbers which may indicate that theyre cross-feeding. Another community may have B. fragilis as the most abundant microbe, with many other microbes in equal, but lower, numbers which could indicate that they are feeding off whatever B. fragilis is making, without any cooperation.

One of the ultimate goals of analyzing human microbiota is to use the presence of certain microbe communities as indicators to identify diseases like Crohns or even specific types of cancer. To test their new method, the Drexel researchers put it up against similar topic modeling procedures that diagnose Crohns and mouth cancer by measuring the relative abundance of certain genetic sequences.

The themetagenomics method proved to be just as accurate predicting the diseases, but it does it much faster than the other topic modeling methods minutes versus days and it also teases out how each microbe species in the indicator community may contribute to the severity of the disease. With this level of granularity, researchers will be able to home in on particular genetic groupings when developing targeted treatments.

The group has made its themetagenomics analysis tools publicly available in hopes of speeding progress toward cures and treatments for these maladies.

It's very early right now, but the more that we understand about how the microbiome functions even just knowing that groups may be acting together then we can look into the metabolic pathways of these groups and intervene or control them, thus paving the way for drug development and therapy research, Rosen said.

This research was supported by the National Science Foundation.

In addition to Rosen and Woloszynek, and Zhengqiao Zhao, PhD, from the Department of Electrical and Computer Engineering; Joshua Mell, MD, from Drexels College of Medicine; and Gideon Simpson, PhD, and Michael OConnor, PhD, from Drexels College of Arts & Sciences, participated in the research.

Read the full paper here:http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0219235

View original post here:
Teams of Microbes Are at Work in Our Bodies. Drexel Researchers Have Figured Out What They're up to. - DrexelNow - Drexel Now

University of Aberdeen researchers hope their study will help help unlock the potential of medicinal cannabis by avoiding side-effectsMike Blake/Reuters

Scientists have identified genetic information that explains why some cannabis smokers suffer depression and psychosis while others experience no negative side-effects.

Researchers from the University of Aberdeen used revolutionary DNA sequencing to study the genes that make cannabis receptors in the brain. These receptors were said to hold the key to understanding why people respond differently to some drugs and could help tailor medical treatments to an individual.

Potential cannabinoid treatments to combat disease, addiction and obesity have been hindered due to the unpredictability of side-effects, which can include depression and psychosis.

Dr Alasdair MacKenzie and Dr Elizabeth Hay, from the school of medicine, medical sciences and nutrition at the university, who led the study, said they hope their discovery will help unlock the potential

Want to read more?

Subscribe now and get unlimited digital access on web and our smartphone and tablet apps, free for your first month.

See the article here:
Genetic switch could be key to psychosis in cannabis smokers - The Times

Professor Sir John Bell, Regius Professor of Medicine at the University of Oxford, delivered a speech at the MHRAs 14th Annual Lecture in London, outlining his vision for the UK life sciences industry. Here, Nikki Withers summarises the key take-home messages from the talk, including how UK researchers and investors should grab the bull by the horns and adopt a less risk-averse approach to research ideas, particularly in the genomics arena.

FROM THE discovery of antibiotics to the 100,000 Genomes Project, the UK has for many years played a leading role in health innovation and medical science. However, to ensure the country continues to be a key R&D player, focus needs to shift towards the next generation of therapeutics.

Looking forward, Professor Bell predicts that scientific research will focus on viral vectors and nucleic acid-based therapies over the coming years. Addressing an audience of about 200 healthcare leaders from the Life Sciences community, he stressed how important it was for the UK to jump on these opportunities. Despite being discovered in Cambridge, the UK was slow to exploit antibody technology to scale, he explained. It is crucially important we dont miss the next platform.

Appointed UK Life Sciences Champion by the Prime Minister in 2011 and author of the Life Sciences Industrial Strategy, Professor Bell has been at the forefront of the life sciences sector for many years. His vision is for the UK to focus on three key areas: genomics, digital health and early diagnosis.

The UK has a long history of genetics research, arguably originating from Darwin and his theory of evolution, according to Professor Bell. We are, without a shadow of a doubt, the leading country in the world in the genomic domain. He highlights two major projects: UK Biobank and Genomics Englands 100,000 Genomes Project, both of which push the UK up the ranks as leaders in genomics research.

UK Biobank is a global health resource that provides health information of 500,000 participants to researchers. Genotyping has been undertaken on all participants, providing a wealth of genomics information. Likewise, the ground-breaking 100,000 Genomes Project, launched by then-Prime Minister David Cameron in 2012 and led by Genomics England, is another example of a UK genetics programme that delivers large-scale data and is accessible for research scientists around the world.

The UK has a spectacular science base. Weve got three of the top 20 medical research programmes and two of the top universities in the world.

However, Professor Bell pointed out that the main challenge associated with this fast-moving research area relates to regulations. Gene editing, nucleic acid-based therapies, these are going to be the next big thing, he said. In genomics we need to regulate an expanding set of genetic tests where the indications and tools change daily, so the big question is how to get them regulated.

His suggestion was for regulators to concentrate on areas where innovation is at the cutting edge. They need to concentrate on speed and efficiency. The industry is frustrated by the lack of pace, particularly by European regulators.

Professor Bell also stressed his desire for researchers and investors to support high-risk science. Generally, investors dont want to invest and there is the dampening effect of peer review. The really interesting and high-risk stuff tends to get killed, he professed.

Concluding the talk, Professor Bell said: The UK has a spectacular science base. Weve got three of the top 20 medical research programmes and two of the top universities in the world. Weve got the largest biotech cluster outside of the US and the largest and most innovative drug regulator in Europe. For a pretty dinky island in the North Sea, were doing pretty well.

We need to get academia, the NHS and industry pharma, biotech, diagnostics and digital aligned to think hard about what the future of the UK might be and to identify the next opportunities to grow our research and economic base in the life sciences.

The future of Life Sciences: Keeping the UK at the forefront of medical and scientific excellence, was hosted by the MHRA on 9 October 2019 at The Kings Fund in London.

Read the original:
Championing genomics in the UK: the next generation - Drug Target Review

SAN DIEGO, Dec. 12, 2019 /PRNewswire/ -- Aspen Neuroscience, Inc. today announced its launch following a $6.5 million seed round led by Domain Associates and Axon Ventures and including Alexandria Venture Investments,Arch Venture Partners,OrbiMedand Section 32 to develop the first autologous cell therapies for Parkinson's disease. Aspen's proprietary approach was developed by the company's co-founders, Jeanne F. Loring, Ph.D., Professor Emeritus and founding director of the Center for Regenerative Medicine at The Scripps Research Institute, and Andres Bratt-Leal, Ph.D., a former post-doctoral researcher in Dr. Loring's lab. The company was initially supported by Summit for Stem Cell, a founding partner and non-profit organization which provides a variety of services for people with Parkinson's disease. Aspen is led by industry veteran Howard J. Federoff, M.D., Ph.D., as Chief Executive Officer.

Parkinson's disease is characterized by the loss of specific brain cells that make the chemical dopamine. Without dopamine, nerve cells cannot communicate with muscles and people are left with debilitating motor problems. Aspen is focusing on human pluripotent stem cells, cultured cells that can become any cell type in the human body. The company's research is specific to induced pluripotent stem cells (iPSCs), which it develops by taking a skin biopsy from a person with Parkinson's disease and turning the tissue into pluripotent stem cells using genetic engineering. Aspen then differentiates the pluripotent stem cells into dopamine-releasing neurons that can be transplanted into that same person (autologous), thereby restoring the types of neurons lost in Parkinson's disease.

As an autologous cell therapy for Parkinson's disease, Aspen's treatment would eliminate the need for immunosuppression because the neurons are transplanted back into the same patient from which they were generated. The use of immunosuppression is necessary with currently available cell therapies for Parkinson's disease and when transplanting cells from one patient to another (allogeneic) to prevent rejection but can pre-dispose the patient to life-threatening complications including infection and add cost to the patient and health system. Aspen is the only company in the world offering an autologous neuron replacement therapy for Parkinson's disease.

Aspen encompasses a powerful executive leadership team including Dr. Federoff who, in addition to his leadership roles at the UC Irvine Health System, was the Executive Vice President for Health Sciences and the Executive Dean of Medicine at Georgetown University. Dr. Federoff also has significant biotech industry experience including co-founding MedGenesis Therapeutix and Brain Neurotherapy Bio, as well as leading the U.S. Parkinson's Disease Gene Therapy Study Group. The company is also proud to announce the addition of several experienced and well-known members to its leadership team including Edward Wirth, M.D., Ph.D., as Chief Medical Officer.

Dr. Wirth currently serves as the Chief Medical Ofcer for Lineage Cell Therapeutics where he oversees clinical development of its two therapeutic programs for spinal cord injuries and lung cancer. He received his M.D. and Ph.D. from the University of Florida in 1994 and remained to conduct postdoctoral research including leading the University of Florida team that performed the rst human embryonic spinal cord transplant in the U.S. Dr. Wirth went on to serve as the Medical Director for Regenerative Medicine at Geron Corporation where the world's rst clinical trial of human embryonic stem cell (hESC)-derived product occurred which demonstrated initial clinical safety.

Drs. Federoff and Wirth are joined by Dr. Loring, as Chief Scientific Officer; Jay Sial, as Chief Financial Officer; Andres Bratt-Leal, Ph.D., as Vice President of Research and Development; Thorsten Gorba, Ph.D., as Senior Director of Manufacturing and Naveen M. Krishnan, M.D., M.Phil., as Senior Director of Corporate Development.

"Aspen is developing a restorative, disease modifying autologous neuron therapy for people suffering from Parkinson's disease," said Dr. Federoff. "We are fortunate to have such a high-caliber scientific and medical leadership team to make our treatments a reality. Our cell replacement therapy, which originated in the laboratory of Dr. Jeanne Loring and was later supported by Summit for Stem Cell and its President, Ms. Jenifer Raub, has the potential to release dopamine and reconstruct neural networks where no disease-modifying therapies exist."

Aspen's lead product (ANPD001) is currently undergoing investigational new drug (IND)-enabling studies for the treatment of sporadic Parkinson's disease. Aspen is also developing a gene-edited autologous neuron therapy (ANPD002) that is in the research stage and targeted toward familial forms of Parkinson's disease beginning with the most common genetic variant in the gene encoding glucocerebrosidase (GBA). Aspen leverages proprietary machine-learning tools and artificial intelligence to ensure quality control during manufacturing and to deliver a safe and reproducible product for each cell line.

"Aspen's financial backing, combined with its experienced and proven leadership team, positions it well for future success," said Kim P. Kamdar, Ph.D., Partner at Domain Associates, one of Aspen's seed investors. "Domain prides itself on investing in companies that can translate scientific research into innovative medicines and therapies that make a difference in people's lives. We clearly see Aspen as fitting into that category, as it is the only company using a patient's own cells for replacement therapy in Parkinson's disease."

About Aspen Neuroscience

Aspen Neuroscience Inc. is a development stage, private biotechnology company that uses innovative genomic approaches combined with stem cell biology to deliver patient-specific, restorative cell therapies that modify the course of Parkinson's disease. Aspen's therapies are based upon the scientific work of world-renowned stem cell scientist, Dr. Jeanne Loring, who has developed a novel method for autologous neuron replacement. For more information and important updates, please visithttp://www.aspenneuroscience.com.

View original content to download multimedia:http://www.prnewswire.com/news-releases/aspen-neuroscience-launches-with-6-5-million-seed-funding-to-advance-first-of-its-kind-personalized-cell-therapy-for-parkinsons-disease-300973830.html

SOURCE Aspen Neuroscience

Follow this link:
Aspen Neuroscience Launches With $6.5 Million Seed Funding to Advance First-of-its-Kind Personalized Cell Therapy for Parkinson's Disease - P&T...

Every minute of every day our bodies are bombarded with millions of different molecules that we breathe, eat and touch including bacteria, viruses, chemicals and seemingly harmless compounds like food and pollen.

For every one of these encounters, our immune system has to decide if the substance is a threat or not, if it is foreign or self and how the body should respond to stay healthy. To do this, we rely on two immune systems working in tandem.

Scientists have discovered a new human autoinflammatory disease that results from a mutation in an important gene in one of these systems.

The syndrome, now known as CRIA (cleavage-resistant RIPK1-induced autoinflammatory) syndrome causes recurring episodes of debilitating and distressing fever and inflammation.

Read more

Our bodys first line of defence is the innate immune system that is effectively a hard wired and fast response, explains Dr Najoua Lalaoui from the Walter and Eliza Hall Institute of Medical Research (WEHI) and the Department of Medical Biology at the University of Melbourne.

This system works in the skin and mucous membranes like the mouth, making sure that any invaders like bacteria are detected and destroyed quickly, she says.

If pathogens do enter the body, the innate immune cells move to the site of infection and physically devour invaders and activate chemical messengers to alert the body.

This can lead to an inflammatory reaction where blood circulation is increased, the affected area becomes swollen and hot, and the person may experience fever. When these chemical messengers are over-active it can result in conditions like colitis, arthritis and psoriasis.

Supporting this system is the adaptive immunity system that involves antibodies that recognise and then train the body to respond to threats. This is our memory immunity and the basis of how vaccinations work.

Scientists from the WEHI, with colleagues at the National Institutes of Health (NIH) in the United States, have been working to understand why patients from three families suffered from a history of painful swollen lymph nodes, fever and inflammation.

The families had a range of other inflammatory symptoms which began in childhood and continued into their adult years.

Read more

This type of repeated fever often indicates an issue with the innate immune system and the same disease in an extended family can indicate genetic changes that are passed from parents to their children, explains Dr Lalaoui.

Previous tests didnt identify any known cause.

But by sequencing the patients genomes, the NIH team identified a mutation in DNA that codes for a molecule known as RIPK that they suspected might cause the disease.

RIPK is a critical regulator of inflammation and the cell death pathway responsible for cleaning up damaged cells or those infected by pathogens.

Professor John Silke from the Walter and Eliza Hall Institute and his team have been studying RIPK1 for more than 10 years. His team had previously shown that damaging the RIPK1 gene could lead to uncontrolled inflammation and cell death.

RIPK1 is a potent controller of cell death, which means cells have had to develop many ways of regulating its activity, Professor Silke says.

In this paper, we showed that one way that the cell regulates its activity is by cleaving RIPK1 into two pieces to disarm the molecule and halt its role in driving inflammation.

In this condition (CRIA), the mutations are preventing the molecule from being cleaved into two pieces, resulting in autoinflammatory disease. This helped confirm that the mutations identified by the NIH researchers were indeed causing the disease, he says.

Read more

He explains that mutations in RIPK1 can drive both too much inflammation as in autoinflammatory and autoimmune diseases and too little inflammation, resulting in immunodeficiency.

There is still a lot to learn about the varied roles of RIPK1 in cell death, and how we can effectively target RIPK1 to treat disease.

In CRIA syndrome, the mutation in RIPK1 overcomes all of the normal checks and balances that exist, resulting in uncontrolled cell death and inflammation, says Dr Steven Boyden from the National Human Genome Research Institute at the NIH.

Dr Boyden says the first clue that the disease was linked to cell death was when they delved into the patients exomes the part of the genome that encodes all of the proteins in the body.

The team sequenced the entire exome of each patient and discovered unique mutations in the exact same amino acid of RIPK1 in each of the three families.

It is remarkable, like lightning striking three times in the same place. Each of the three mutations has the same result it blocks cleavage of RIPK1 which shows how important RIPK1 cleavage is in maintaining the normal function of the cell, says Dr Boyden.

Dr Lalaoui said the WEHI researchers then confirmed the link between the RIPK1 mutations and CRIA syndrome in laboratory models.

Read more

We showed that mice with mutations in the same location in RIPK1 as in the CRIA syndrome patients, had a similar exacerbation of inflammation, she says.

Dr Dan Kastner from NIH widely regarded as the father of autoinflammatory disease says colleagues had treated CRIA syndrome patients with a number of anti-inflammatory medications, including high doses of corticosteroids and biologics, compounds that block specific parts of the immune system.

And although some of the patients markedly improved, others responded less well or had significant side effects.

Understanding the molecular mechanism by which CRIA syndrome causes inflammation provides an opportunity to get right to the root of the problem, Dr Kastner says.

Dr Kastner noted that RIPK1 inhibitors, which are already available on a research basis, may provide a focused, precision medicine approach to treating patients.

RIPK1 inhibitors may be just what the doctor ordered for these patients. The discovery of CRIA syndrome also suggests a possible role for RIPK1 in a broad spectrum of human illnesses, such as colitis, arthritis and psoriasis.

Banner: WEHI

Read more:
The genetic mutation behind a new autoinflammatory disease - Pursuit

Cannadabis Medical INC they intend to create a healthier and more consciously aware environment for the cannabis industry, and its participants, to thrive in.

Did you know that Cannadabis are Partners with us? Discover their featured Partner Page about a healthier, environmentally conscious cannabis industry.

The company is a family run company that was founded in Humboldt, Saskatchewan.

Founders, Alexander Calkins, BSc and Markus Li, P.Chem, MBA, are personally and emotionally invested in the science of cannabis. They each have family members that are dealing with incurable ailments, complications of which can often become fatal.

In the search for natural products that will improve the quality and longevity of life, the founders began working with cannabis. While there is no likelihood of a cure, the symptom management has been very positive for their family members. After witnessing the improvements, Cannadabis founders Calkins and Li, have dedicated themselves to furthering the medical cannabis movement.

Calkins and Li both have backgrounds in technical science and business. They are experienced cultivators and have a strong understanding of energy systems (practically essential for a power-hungry industry), process automation, and large-scale development.

Their familiarity with multi-industry supply chains has leveraged them into a cannabis development that is simultaneously high-tech, old school, and simple.

Through observation of established global industries, Cannadabis is building a multi-faceted business model based on sustainable practices, a strong genetics portfolio, disruptive technologies, hyper-specialisation, and holistic production.

Driven by a passion to help others in need, Calkins and Li took it upon themselves to bring their methods and expertise to the cannabis world. They recognise and praise the patient independence that medical cannabis can provide.

While they champion the practice of homegrown medicine, they have obligated themselves to providing the safest and highest quality medical products to those who are unable to grow for themselves.

Once Cannadabis has perfected its organic growing system, they will build and operate all future cultivation sites according to (EU) GMP and ISO:9001 2015 standards. By adopting these standards, Cannadabis will have the ability to share their cultivated passion with the world.

To meet the sanitary requirements of GMP and processing limitations of an organic certification, Cannadabis will be using a combination of reactive oxygen, electrolysed water, and radio frequency pasteurisation technologies.

Being a medically focused company, Cannadabis recognises that medical consumers have turned to cannabis because they are looking for natural remedies and are becoming increasingly weary of synthetic medicines.

For Cannadabis, producing medical cannabis using anything other than organic methods would transgress the fundamental sentiment that drives the global, medical movement. That is why Cannadabis is committed to attaining internationally recognised organic certifications on expanded production.

The companys flagship facility is intended to be an R&D focused proving ground for state-of-the-art organic cultivation methods. Cannadabis currently uses an inhouse blended soil, made only with organic ingredients. Their living soil has the benefit of creating terpene dense medicine, reducing cost, and simplifying processes.

With all the nutrients available in the soil, the plants require only water from transplant to harvest. Additionally, the growing medium and all organic waste can be recycled through vermicomposting, further reducing long term costs and needless waste.

Cannadabis will adopt various technologies to reduce energy demand and environmental impact. In addition to using LEDs and solar panels, Cannadabis will use combined heat and power (CHP) (or cooling combined heat power (CCHP)) at their cultivation facilities. CHP units burn natural gas to generate power and the waste heat is used to heat water and the workspace. CHPs are quickly becoming popular for reducing carbon emissions. In certain applications, CHPs reduce carbon emissions by 30-40%, compared to when power is taken from the grid.

Cannadabis will also divert the combustion CO2 into the growing space. CO2 supplementing supercharges growth naturally, increasing yield by 30-60%, and further reducing the carbon emissions from power generation. In the future, expanded cultivations may integrate pyrolysis of waste biomass, which will supply power and nutrient dense biochar to the living soil.

Cannadabis is aspiring to build a unique indoor growing system that uses a combination of solar power, water recycling, CHP (CCHP), pyrolysis, CO2 supplementation and vermicompost to create a no waste, carbon neutral, minimal input, self-regenerating nutrient, off grid, medical grade, organic, indoor cultivation.

Calkins and Li hope to validate the system and then apply the techniques to food cultivation; this type of system could revolutionise the food production in remote locations, like the northern territories, Alaska and would deliver food supply independence to small communities or reservations. Where biomass is abundant, this system would produce all year, requires only labour as inputs, self-generate power off-grid, and would also be carbon negative over extended time frames.

On their path to improving growing efficiency, Cannadabis has developed proprietary tissue culture methods specifically for cannabis. These methods are based upon the decades old horticultural practice that has been essential for the sterile propagation of ornamental and food cultivars; non seed propagation.

Developing an inhouse tissue culture system has the following benefits:1

Tissue culture revitalises cultivars and produces more vigorous plants Regeneration from meristem rids systemic disease; Propagation is significantly more efficient; Starting with 100 traditional cuttings; able to produce 70,000 annual clones; Start with 200 tissue culture vials; produce 2 million annual clones; Uses 1/10 the space of traditional cloning; Per square foot, tissue culturing is >100x more efficient; and Two million annual clones could be produced in less than 3000 square feet.

1000 mother cultivars could be stored inside a refrigerator with no care or maintenance for months, sometimes over a year; and Pest invasion would not affect mother cultures (many cultivators without tissue culture have lost their entire genetic inventory to viruses and fungi).

Cannadabis will be sharing its tissue culture methods with industry members who want to stay one step ahead of pests and systemic disease. Following more development, they will also be making their organic formulations available.

Having collected and grown a large variety of cultivars, both through seed and clone, the Cannadabis founders have noticed a distinct lack of quality in the genetics market. Over time, most of the popular cultivars of the world have been slowly degraded by deleterious breeding practices like selfing (feminising), backcrossing, and poor mother plant maintenance which promotes genetic drift.

The current genetics market is rife with breeders that take prized clones and spray them with colloidal silver to produce feminised seed, or they are crossed onto their own cultivars and backcrossed until stable seed is produced.

While these name sake creations may capture some of the qualities of the original strain, like trichome density or terpene profile, the progeny will lack the genetic diversity needed to produce healthy plants. Often, these weakened strains have reduced yield, potency, and pest resistance. In response to this, Cannadabis has focused on breeding their own high yield, high potency, flavour dense strains for commercial production.

The Cannadabis team is eager to unveil their propriety strains to the domestic and international medical markets. Over the past few years, the founders have started breeding their own cultivars. Currently, the team has focused on a selection of stabilised true breeds (landrace or F5+) for creating original F1 breeds.

Where the F1 generation is created by breeding male and female plants that are distinctly unique from each other; traditional F1s are created by crossing landrace indicas with landrace sativas.

These crosses need to be done with highly stable and uniquely different parents to produce a true F1 progeny that has abundant hybrid vigour. A plant with true hybrid vigour will typically have higher potency, increased pest resistance, and a higher yield than both parent plants; on average yield can be as high as 20% more than either parent.

Due to the nature of the F1 progeny, very few breeders release true F1 seeds. If highly stable progenitors are not used, the seedstock will be incredibly variable, which is unfavourable for consumers, who typically want consistency in their seed. However, as commercial cultivators, Cannadabis believes that F1 hybrids are essential for producing at large scale. The breeding and phenotyping can be a long and arduous process, the fruits of labour are not without commercial benefit.

Building upon the tissue culture and breeding practices, Cannadabis is quickly developing polyploidisation methods for creating ultra-premium cultivars. Polyploidisation is another common horticultural practice that Cannadabis expects to apply to their cannabis breeding projects.

Polyploidisation is a naturally occurring mechanism where the chromosomes of the plant cells become doubled within the same nucleus. This mechanism has played a significant role in speciation of crops, occurring frequently in nature, usually due to stress response.

In the 100 years since scientists discovered polyploidy, there has been rapid development of polyploid breeds. It is estimated that up to 80% of all flowering plants have polyploid varieties.2 Common polyploid cultivars includes wheat, coffee, banana, strawberry, potato, etc.

Polyploidy has been researched since the early 1900s. Scientists first used heat and electrical stress to induce those mechanisms. Today polyploidy is more commonly, and consistently, induced with radiation and stressing chemicals. Interestingly, induced polyploidy is explicitly exempt by most organic certification bodies. These types of breeds typically do not fall under genetically modified until foreign, non-similar species, DNA is introduced to the plant cell.

These polyploids are called autopolyploid (same species), and plants made with dissimilar species are called allopolyploids. Cannadabis will also be exploring organic permitted cell fusion; this would allow breeding with two male plants, or two female plants.

In the past, the following horticulture benefits have been derived from polyploidy and cell fusion, which Cannadabis hopes to similarly apply to the cannabis plant:3

The same can apply to cannabis. Strains can be developed that would never seed regardless of direct pollination; massive utility available to outdoor or indoor cultivators with seeding problems.

Cannadabis hopes to release their first polyploid strains in late 2020.

Cannadabis has begun manufacturing premade tissue culture mediums and are currently distributing them to Western Canadian horticulture stores and Amazon Marketplace; the mediums are a standard blend that works on 95%+ of the founders cultivars. The founders tissue culture experience is being provided to the public in both consumer and commercial grade products.

The introductory products show unfamiliar users how to do tissue culture at home, using proven methods that do not require expensive laboratory equipment. Besides what comes in the starter kit, the everyday home grower will usually have all the remaining materials at home. Commercial format mediums are intended for growers that want the best value and space savings.

Cultivators of any background can find information or help on tissue culture through the Cannadabis homepage. They are posting helpful videos and literature on cannabis tissue culture and hope to share the benefits with every grower. All horticulturalists, cannabis or not, can benefit from having their cloning area be 100x more efficient, through stackable containers. Furthermore, their mother plants can easily be maintained with minimal care. 100-1000 mother cultures can be stored within a refrigerator for 4-8 months, no adding nutrient or water. For larger cultivators, Cannadabis provides PGR matrices to more easily troubleshoot difficult cultivars. They also will custom blend and sterilise mediums to customer preference.

Cannadabis has begun developing an automated cell culture process for mass propagation of cultivars. The economies of scale of which are expected to change the supply chain of the entire cannabis industry. Automated cell culturing will provide starting materials to the industry at a fraction of the cost of inhouse cloning. Clones produced through cell culturing will also have the benefit of being totally sterile and free from disease.

Cannadabis has been offered an NRC-IRAP grant for initial developments of the process and are in early negotiations with a Canadian cannabis company to commercialise. The founders are expecting to file patents, mid 2020, and begin construction of a commercial scale process by mid-2021. Cannadabis anticipates that a 5000 sq ft facility will produce 5+ million clones annually, with minimal labour.

The project is looking to possibly incorporate the production of artificial seeds, which would simplify transportation and ease of storage for cultivators. They will also be developing cryogenic preservation methods. Cultivators around the world are encouraged to reach out to Cannadabis if they are looking to simplify their process, access cell culture benefits, and maximise growing space.

Working with Cannadabis cultured clones will be the most affordable, safe, and efficient way of acquiring starting material. Their services would include meristem culturing to remove systemic disease, and long-term storage of genetic inventory. Partners who end up with a pest could rest easy knowing their mother cultures will be perfectly preserved in tissue culture, and fifty thousand clones for the next crop are still on the way.

Cannadabis Medical and Delta 9 Cannabis have teamed up to provide an affordable, turnkey, tissue culture laboratory, complete with operating procedures, equipment, and cannabis medium recipes.

The two companies have co developed this system for their own commercial use and have recently made the system available for other cultivators. Both companies have recognised that the cannabis industry is still reliant on black market methods of propagation, and as a result, there have been countless incidents of crop and genetic loss in the legal industry; many of the stories circulating are understandably refuted by the companies experiencing such loss.

Rather than ignore the inevitable pest problems, the two companies are going toe to toe with mother nature, developing half century old technology and making it specifically for cannabis. Hopefully delivering the same modicum of control to the rest of the industry; cultivators slow to develop tissue culture science may soon find their genetics and crop totally destroyed by a single, often microscopic pest. On a commercial scale, these pests become essentially impossible to remove without the use of tissue culture.

With feet rooted in genuine care, Cannadabis and Delta 9 are prepared and excited to deliver a tissue culturing system to the global cannabis industry. They recognise the value and utility available to growers, and they also recognise that learning tissue culturing can feel out of reach for cultivators with no prior knowledge, or excess funding to hire an inhouse specialist.

Instead of missing out or paying specialists, cultivators can rely on Cannadabis and Delta 9 to deliver a ready to use laboratory, the development of which was based on maximising value for the growers.

The laboratory comes with only bare essentials and extensive, yet simple, operating procedures. Training materials will detail cannabis specific mediums, sanitation protocols, along with troubleshooting methods for finicky cultivars; an inexperienced grower will be comfortably blending and using mediums on the same day of commissioning. The whole system, equipment and all, will be much more affordable than hiring a tissue culture specialist.

Over the next three years, Cannadabis will be working to establish an expanded cultivation with the hope of supplying medical, organic, indoor grown cannabis to domestic and international markets.

They will also pioneer an original cell culture process that expects to be the most affordable source for starting materials in the world; Cannadabis is especially excited to deliver their polyploid cultivars as starting materials to industry members.

Cannadabis would like to offer an open invitation to all scientists, entrepreneurs, and industry professionals for collaboration. We are actively seeking partners who share a similar vision for the cannabis industry. Any professionals who are driven by a sense of genuine care and have a passion for cannabis medicine are encouraged to reach out.

References

1 hempindustrydaily.com/hemp-cultivators-tissue-culture-increase-propagation-preserve-genetics/2 Meyers, L. A., and Levin, D. A. (2006). On the abundance of polyploids in flowering plants. Evolution 60, 11981206. doi: 10.1111/j.0014 3820.2006.tb01198.x3 http://www.slideshare.net/ranganihennayaka/plant-polyploids4 http://www.frontiersin.org/articles/10.3389/fpls.2019.00476/full5 plantbreeding.coe.uga.edu/index.php?title=5._Polyploidy

Alexander CalkinsCEOCANNADABIS Medical INC+1 306 552 4242alexander@cannadabismedical.caTweet @cannadabiscannadabismedical.ca

This article will appear in the first issue ofMedical Cannabis Networkwhich will be out in January.Clickhereto subscribe.

Read more from the original source:
Cannadabis: tissue culture and the future of cannabis cultivation - Health Europa

"These guidelines are as inclusive as possible, wherever there's strong, unbiased evidence to back up our recommendations," said Mary B. Daly, MD, PhD, FACP, Fox Chase Cancer Center, Chair of the NCCN Guidelines Panel for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic. "The guidelines include genes that have been found to increase cancer-susceptibility. These NCCN Guidelines still have a strong focus on BRCA1 and 2 mutations, but also now include other high and moderate penetrance genes associated with breast, ovarian, and pancreatic cancer. We continuously review any new data on genes that might increase a person's risk of getting cancer or impact the effectiveness of their treatment."

The updated guidelines are concentrated around simplified criteria to clarify the genetic testing process. For example, in a newly-added guide for individuals of Ashkenazi Jewish ancestry who have not been diagnosed with cancer, genetic testing may be offered for the three Ashkenazi Jewish founder mutations in the context of a long-term research study, regardless of family history. These individuals should be encouraged to consult with a cancer genetics professional.

The NCCN Guidelines for Genetic/Familial High-Risk Assessment are organized by both disease and syndrome type, and also now include streamlined information on appropriate subsequent steps for persons who meet criteria for genetic testing. The panel acknowledges that genetic mutations can impact the approach to cancer treatment, and the guidelines now state that testing may be clinically indicated if it will aid in systemic therapy decision-making.

"Genetic testing is becoming increasingly utilized in oncology because of its potential to impact surgical decisions and chemotherapy," explained Robert Pilarski, MS, LGC; MSW, Licensed Genetic Counselor, Professor, Clinical Internal Medicine, The Ohio State University Comprehensive Cancer Center, Vice-Chair of the NCCN Guidelines Panel for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic. "At the same time, the complexity of this testing is increasing, with a growing number of genes and tests available,a limited understanding of the management implications of some of the newer genes, and even uncertainty over the implications of mutations in well-established genes in some situations (for example in a condition known as 'mosaicism,' in which the mutation is not present in all of the cells of the body). Because of this, the NCCN Guidelines continue to highlight the critical importance of genetic counseling for patients prior to undergoing genetic testing to ensure that patients are fully informed of the test implications."

Pilarski also offered an important word of caution about the potential risks from direct-to-consumer genetic testing: "More and more patients are presenting to clinic having already had themselves tested through direct-to-consumer labs. Providers need to be aware that the tests offered by many of these labs are not equivalent to traditional genetic testing, and the results may need to be confirmed in another laboratory before being used for clinical care."

The guidelines recommend all pancreatic cancer patients get genetic testing, and the recent update now includes more information about which genes are associated with pancreatic cancer recommendations. Genetic testing in pancreatic cancer can help determine which treatments would be most effective (e.g. PARP inhibitors) and if family members would benefit from screening and preventive action.

"There's been an explosion of recent data showing that roughly 4-10% of individuals with pancreatic cancer harbor inherited genetic mutations, including BRCA1, BRCA2, ATM, the Lynch syndrome genes, and others," said Matthew B. Yurgelun, MD, Dana-Farber/Brigham and Women's Cancer Center, Member of the NCCN Guidelines Panel for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic. "Such data have, surprisingly, shown that classic 'high-risk' features of inherited cancer risk (e.g. young age at diagnosis, strong family histories of cancer) are often absent in individuals with pancreatic cancer who carry these mutations. Based off of these data, there is now a compelling reason for all individuals with pancreatic cancer to be offered genetic counseling and germline testing for such variantsparticularly given the possibility that their at-risk family members could greatly benefit from known, effective cancer risk-reducing interventions (e.g. surgical removal of the ovaries for female BRCA1/2 mutation carriers). Emerging data have also begun to suggest possible benefits to pancreatic cancer screening in select high-risk individuals who harbor such mutations. These new guidelines address many of the important nuances and limitations of this exciting and rapidly evolving body of literature."

The NCCN Guidelines for Genetic/Familial High-Risk Assessment are created and maintained by an interdisciplinary panel of experts from the alliance of 28 leading cancer centers that comprise NCCN. NCCN panels also include patients and advocates to make sure treatment recommendations meet the needs of people with cancer and their caregivers.

"Participating on the NCCN panel allows FORCE to share the real-world experiences of patients making complex, and often agonizing medical decisions about hereditary cancer treatment and risk management," said Sue Friedman, DVM, Executive Director, Facing Our Risk of Cancer Empowered (FORCE), Member of the NCCN Guidelines Panel for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic. "As an advocacy organization for people and families affected by hereditary cancer, we see the importance of having standardized guidelines. These guidelines are a critical piece of informed decision-making; we frequently direct our community to NCCN for up-to-date, clear, and credible information developed by experts in the field."

NCCN Guidelines are the recognized standard for clinical policy in cancer care and are the most thorough and frequently updated clinical practice guidelines available in any area of medicine. The intent of the NCCN Guidelines is to assist in the decision-making process of individuals involved in cancer careincluding physicians, nurses, pharmacists, payers, patients and their familieswith the ultimate goal of improving patient care and outcomes. In addition to covering at least 97 percent of cancers affecting patients in the United States, there are also NCCN Guidelines for detection, prevention, risk-reduction (including smoking cessation), supportive care (including the management of pain, distress, and fatigue), and guidelines for specific populations (including children and young adults).

NCCN Guidelines are available free-of-charge for non-commercial use at NCCN.org, or via the Virtual Library of NCCN Guidelines App.

About the National Comprehensive Cancer NetworkThe National Comprehensive Cancer Network (NCCN) is a not-for-profit alliance of 28 leading cancer centers devoted to patient care, research, and education. NCCN is dedicated to improving and facilitating quality, effective, efficient, and accessible cancer care so patients can live better lives. Through the leadership and expertise of clinical professionals at NCCN Member Institutions, NCCN develops resources that present valuable information to the numerous stakeholders in the health care delivery system. By defining and advancing high-quality cancer care, NCCN promotes the importance of continuous quality improvement and recognizes the significance of creating clinical practice guidelines appropriate for use by patients, clinicians, and other health care decision-makers around the world.

The NCCN Member Institutions are: Abramson Cancer Center at the University of Pennsylvania, Philadelphia, PA; Fred & Pamela Buffett Cancer Center, Omaha, NE; Case Comprehensive Cancer Center/University Hospitals Seidman Cancer Center and Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; City of Hope National Medical Center, Duarte, CA; Dana-Farber/Brigham and Women's Cancer Center | Massachusetts General Hospital Cancer Center, Boston, MA; Duke Cancer Institute, Durham, NC; Fox Chase Cancer Center, Philadelphia, PA; Huntsman Cancer Institute at the University of Utah, Salt Lake City, UT; Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance, Seattle, WA; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL; Mayo Clinic Cancer Center, Phoenix/Scottsdale, AZ, Jacksonville, FL, and Rochester, MN; Memorial Sloan Kettering Cancer Center, New York, NY; Moffitt Cancer Center, Tampa, FL; The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute, Columbus, OH; O'Neal Comprehensive Cancer Center at UAB, Birmingham, AL; Roswell Park Comprehensive Cancer Center, Buffalo, NY; Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis, MO; St. Jude Children's Research Hospital/The University of Tennessee Health Science Center, Memphis, TN; Stanford Cancer Institute, Stanford, CA; UC San Diego Moores Cancer Center, La Jolla, CA; UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA; University of Colorado Cancer Center, Aurora, CO; University of Michigan Rogel Cancer Center, Ann Arbor, MI; The University of Texas MD Anderson Cancer Center, Houston, TX; University of Wisconsin Carbone Cancer Center, Madison, WI; Vanderbilt-Ingram Cancer Center, Nashville, TN; and Yale Cancer Center/Smilow Cancer Hospital, New Haven, CT.

Clinicians, visit NCCN.org. Patients and caregivers, visit NCCN.org/patients. Media, visit NCCN.org/news. Follow NCCN on Twitter @NCCN, Facebook @NCCNorg, and Instagram @NCCNorg.

Media Contact: Rachel Darwin267-622-6624darwin@nccn.org

SOURCE National Comprehensive Cancer Network

http://www.nccn.org

Read the rest here:
Updated Genetic Screening Guidelines Published by National Comprehensive Cancer Network Feature Emerging Evidence on Personalized Medicine -...

BETHESDA, Md., Dec. 4, 2019 /PRNewswire/ --The American College of Medical Genetics and Genomics (ACMG) heads to a new destination in sunny San Antonio, Texas in 2020. Named one of the fastest growing meetings in the USA by Trade Show Executive Magazine, the ACMG Annual Clinical Genetics Meeting continues to provide groundbreaking research and news about the latest advances in genetics, genomics and personalized medicine. To be held March 17-21, the 2020 ACMG Annual Meeting will feature more than 40 scientific sessions, 3 Short Courses, workshops, TED-Style talks and satellite symposia, and over 800 poster presentations on emerging areas of genetic and genomic medicine.

Interview those at the forefront in medical genetics and genomics, connect in person with new sources and get story ideas on the clinical practice of genetics and genomics in healthcare today and for the future. Learn how genetics and genomics research is being integrated and applied into medical practice.

Topics include gene editing, cancer genetics, molecular genomics, exome sequencing, pre- and perinatal genetics, biochemical/metabolic genetics, genetic counseling, health services and implementation, legal and ethical issues, therapeutics and more.

Credentialed media representatives on assignment are invited to attend and cover the ACMG Annual Meeting on a complimentary basis. Contact Kathy Moran, MBA at kmoran@acmg.net for the Press Registration Invitation Code, which will be needed to register at http://www.acmgmeeting.net.

Abstracts of presentations will be available online in January 2020. A few 2020 ACMG Annual Meeting highlights include:

Program Highlights:

Cutting Edge Scientific Concurrent Sessions:

Three half-day Genetics Short Courses on Monday, March 16 and Tuesday, March 17:

Photo/TV Opportunity: The ACMG Foundation for Genetic and Genomic Medicine will present bicycles to local children with rare genetic diseases at the Annual ACMG Foundation Day of Caring on Friday, March 20 from 10:30 AM 11:00 AM at the Henry B. Gonzlez Convention Center.

Social Media for the 2020 ACMG Annual Meeting: As the ACMG Annual Meeting approaches, journalists can stay up to date on new sessions and information by following the ACMG social media pages on Facebook,Twitter and Instagram and by usingthe hashtag #ACMGMtg20 for meeting-related tweets and posts.

Note be sure to book your hotel reservations early.

The ACMG Annual Meeting website has extensive information at http://www.acmgmeeting.net.

About the American College of Medical Genetics and Genomics (ACMG) and the ACMG Foundation for Genetic and Genomic Medicine (ACMGF)

Founded in 1991, the American College of Medical Genetics and Genomics (ACMG) is the only nationally recognized medical society dedicated to improving health through the clinical practice of medical genetics and genomics and the only medical specialty society in the US that represents the full spectrum of medical genetics disciplines in a single organization. The ACMG is the largest membership organization specifically for medical geneticists, providing education, resources and a voice for more than 2,300 clinical and laboratory geneticists, genetic counselors and other healthcare professionals, nearly 80% of whom are board certified in the medical genetics specialties. ACMG's mission is to improve health through the clinical and laboratory practice of medical genetics as well as through advocacy, education and clinical research, and to guide the safe and effective integration of genetics and genomics into all of medicine and healthcare, resulting in improved personal and public health. Four overarching strategies guide ACMG's work: 1) to reinforce and expand ACMG's position as the leader and prominent authority in the field of medical genetics and genomics, including clinical research, while educating the medical community on the significant role that genetics and genomics will continue to play in understanding, preventing, treating and curing disease; 2) to secure and expand the professional workforce for medical genetics and genomics; 3) to advocate for the specialty; and 4) to provide best-in-class education to members and nonmembers. Genetics in Medicine, published monthly, is the official ACMG peer-reviewed journal. ACMG's website (www.acmg.net) offers resources including policy statements, practice guidelines, educational programs and a 'Find a Genetic Service' tool. The educational and public health programs of the ACMG are dependent upon charitable gifts from corporations, foundations and individuals through the ACMG Foundation for Genetic and Genomic Medicine.

Kathy Moran, MBAkmoran@acmg.net

View original content to download multimedia:http://www.prnewswire.com/news-releases/press-registration-for-the-2020-acmg-annual-clinical-genetics-meeting-is-now-open-300969157.html

SOURCE American College of Medical Genetics and Genomics

Read the rest here:
Press Registration for the 2020 ACMG Annual Clinical Genetics Meeting Is Now Open - P&T Community

The GenomeAsia 100K consortium analyzed the genomes of 1,739 people, which represents the widest coverage of genetic diversity in Asia to date.

The study covers 64 different countries and provides what the authors call the first comprehensive genetic map for Asia that will guide scientists in studying diseases unique to Asians, improve precision medicine and identify drugs that may carry higher risk of adverse reactions for certain ethnic groups.

Despite forming over 40 per cent of the worlds population, Asian people have previously accounted for only six per cent of the worlds recorded genome sequences.

The goal of GenomeAsia 100K, which launched in 2016, is to better understand the genome diversity of Asian ethnicities by sequencing 100,000 genomes of people living in Asia. It is a non-profit consortium hosted by Nanyang Technological University, Singapore (NTU Singapore), the only academic member. Its three other members are Macrogen based in South Korea, Genentech, a member of the Roche Group in United States, and MedGenome from India/US.

NTU Professor Stephan C. Schuster, the consortiums scientific chairman and a co-leader of the study, explained the significance of GenomeAsia 100Ks initial findings on the vast genomic diversity in Asia: To put it into context, imagine we looked at all people of European and based on the level of their genetic diversity, observed that they could all be grouped into just one ancestral lineage or population. Now, if we took that same approach with our new data from people of Asian, then based on the much higher levels of genetic diversity observed we would say that there are 10 different ancestral groups or lineages in Asia.

Schuster added, GenomeAsia 100K is a significant and far-reaching project that will affect the well-being and health of Asians worldwide, and it is a great honour for Singapore and NTU to be hosting it.

Executive Chairman of GenomeAsia 100K, Mahesh Pratapneni said, The publication of this pilot study is a first milestone for GenomeAsia 100K, which is an unprecedented collaboration between academia and industry leaders in the field of genomics. We are certain more partners will join GenomeAsia 100K to accelerate medical breakthroughs for people of Asian heritage.

Chairman and CEO of MedGenome, the largest genomics and molecular diagnostics provider in South Asia with facilities in the US, Singapore and across India, Sam Santhosh, said, "We are excited that over 1000 whole genome sequence data from the Indian sub-continent will now be available to researchers; this is an initial step in covering the underrepresented geographies."

Prof Jeong-Sun Seo, at Seoul National University Bundang Hospital Consortium scientific co-chair and Chairman of Macrogen, said, I hope this Asian-focused study serves as a stepping stone for the democratization of health care and precision medicine in Asia.

How the database of Asian genomes was formed

Over the course of the last three decades prior to the pilot project, thousands of blood and saliva samples have already been collected by scientists and anthropologists from donors across Asia in hopes that one day, a deeper analysis to gain insights into the Asian community can be done.

Of particular interest were participants from remote and isolated communities, who have long been the subjects of study by anthropologists but have not yet undergone genomic analysis, until the GenomeAsia 100K project was kickstarted.

The pilot study included 598 genomes from India, 156 from Malaysia, 152 from South Korea, 113 from Pakistan, 100 from Mongolia, 70 from China, 70 from Papua New Guinea, 68 from Indonesia, 52 from the Philippines, 35 from Japan, and 32 from Russia.

Genomic DNA extracted from the blood and saliva samples was then sequenced in laboratories of the four consortium members in the US, India, South Korea and Singapore. The digital sequencing data were subsequently sent to Singapore for processing and storage.

Singapore was selected by the consortium as the host, as the country offered good travel connections for collaborating scientists, strong supercomputing facilities to crunch the data, and the required cybersecurity standards in its data centre for handling sensitive genetic data.

The combined data was compiled and analyzed by NTU scientists, including Assistant Professor Hie Lim Kim, a population genomics expert at the Asian School of The Environment, with the help of the National Supercomputing Centre Singapore (NSCC) and international collaborators.

Different Asian ethnic groups respond differently to mainstream drugs

Every person has approximately 3.2 billion different nucleotides, or building blocks, in their genome, which form their DNA code.

Its estimated that for the genomes of any two people, 99.9 per cent of this code is the same and on average, 0.1 per cent or three million nucleotides, are different between them.

This genetic variance help humankind colonize the most diverse environments on the planet and make it resilient to disease, but it also results in differential response to many medicines.

Genetic variance is the reason we are distinctively different from each other including differences in the diseases that each of us suffer from during our lifetimes. Understanding these differences is the most important source of clues that we have for driving the discovery of innovative new medicines, said Dr Andrew Peterson, an author of the paper and an expert in the use of genetics to drive drug discovery.

Peterson was head of Molecular Biology at Genentech while this work was being carried out, is now Chief Scientific Officer at MedGenome, where he leads drug discovery efforts at MedGenomes Seven Rivers Genomic Medicines division.

The frequencies of known genetic variants related to adverse drug response were analyzed for the genomes collected in this study.

For example, warfarin, a common anticoagulant drug prescribed to treat cardiovascular diseases, likely has a higher than usual risk of adverse drug response for people carrying a certain genetic variant. This particular genetic variant has a higher frequency to appear in those with North Asian ancestry, such as Japanese, Korean, Mongolian or Chinese.

Using data analysis, scientists can now screen populations to identify groups that are more likely to have a negative predisposition to a specific drug.

Knowing a persons population group and their predisposition to drugs is extremely important if personalized medicine is to work, stressed Prof Schuster: For precision medicine to be precise, you need to know precisely who you are.

Hie Lim Kim, who leads the projects efforts in population genetics, added: Only by sequencing the entire genome of an individual can a persons ancestry and genetic background be known. Their genome explains why some people are afflicted by certain diseases while others arent. Scientists know that there is no single drug that works well for everybody and our latest findings not only reinforce this, but suggest how specific groups could be harmed by specific medicines.

Moving forward, the GenomeAsia 100K will continue to collect and analyze up to 100,000 genomes from all of Asias geographic regions, in order to fill in the gaps on the worlds genetic map and to account for Asias unexpected genetic diversity.

Reference

GenomeAsia100K Consortium. (2019) The GenomeAsia 100K Project enables genetic discoveries across Asia. Nature. DOI: https://doi.org/10.1038/s41586-019-1793-z

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

See the original post here:
Insights into Asian Ancestry and Genetic Diversity - Technology Networks

Rapid advances in telomere biology are paving the way to new clinical applications that promise better diagnosis and treatment options in select patients. Scientists understanding about the role of telomerescaps at the ends of chromosomes that prevent attrition of DNAhas progressed to the point that telomere measurements are being used in diagnostic workups at some medical centers. Broader dissemination of this type of analysis will go hand-in-hand not only with a deeper understanding of the link between telomere length and health and disease but also more standardized testing methods and parameters. Expanding the use of telomere testing also will depend on better coordinated care among clinical disciplines that have not traditionally worked together, according to Mary Armanios, MD, professor of oncology, genetic medicine, molecular biology and genetics, and pathology at Johns Hopkins University in Baltimore.

The causal role telomeres play in aging and age-related diseases has been known for decades. However, new studies now reveal that extreme short or long telomere lengths are associated with specific heritable diseases and cancers. This knowledge, a pivotal advance, has added urgency to the quest to accurately measure telomere length and define clinically relevant short and long thresholds. With the advent of precision genomics, we have the opportunity to identify and manage these disorders for the benefit of patients, said Mrinal Patnaik, MBBS, an associate professor of medicine and oncology and a consultant hematologist at the Mayo Clinic in Rochester, Minnesota.

Telomeres shorten every time a cell divides, naturally shortening with age and at a certain point signaling cells to stop dividing and become senescent. However, when genes responsible for telomere synthesis, trafficking, maintenance, and for telomerase function are perturbed, accelerated telomere shortening leads to a group of genetic disorders called short telomere syndromes (STS). Notably, although 13 causative genes have been identified, these account for only about 40% of STS cases. The fact that more than half of our patients with short telomeres do not have detectable gene mutations on sequencing panels indicates that we havent yet discovered all the mutations that affect telomere length, said Patnaik.

STS encompass disparate clinical manifestations across multiple organ systems including immunodeficiency, idiopathic pulmonary fibrosis and emphysema, esophageal stenosis and enterocolitis, hepatic fibrosis and cirrhosis, and bone marrow failure. Anytime you see a triad of symptoms that include premature greying of hair, fibrotic involvement of lung and liver, and bone marrow failure, it should raise flags as a potential STS, said Patnaik.

In contrast, mutations that lengthen telomeres cause long telomere syndromes. These are associated with a high cancer risk: glioma and familial melanoma, in particular. Insights from genome-wide association studies have identified genetic variants in telomere-related genes concurrent with these cancers, further strengthening the telomere-cancer link.

Diagnosing patients with telomere length disorders is challenging, especially STS, given their broad clinical spectrum. The Telomere Clinic at Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, which Armanios leads, offers a telomere measurement service to clinicians and provides multidisciplinary care to patients with telomere-related disorders. Our goal was to establish a clinically reliable tool for telomere length measurement in a hospital setting and make it available to physicians and their patients for precise diagnosis and treatment recommendations, she said.

Patients with severe STS often need organ transplants as a result of end-organ failure. Telomere-related testing can offer these patients a more tailored approach to managing their disease, especially in pre-transplant settings. For example, most patients with STS cant tolerate standard doses of radiation and cytotoxic therapies; recognizing this enables physicians to choose a different conditioning regimen. Also, dysfunctional telomere-related gene(s) are passed through autosomal or X-linked transmission; physicians can therefore screen potential donorsoften patients close relativesto make sure they do not carry these same faulty gene(s).

Armanios and her team recently reported using telomere length as a diagnostic tool to identify patients with STS (Proc Natl Acad Sci U S A 2018;115:E235865). After establishing normal telomere ranges from a healthy control population and determining that telomere measurements have tight concordance and reproducible upper and lower boundaries across populations, they also found that most patients with variants in telomere-related genes had short telomere lengths. In addition, they observed a correlation between the severity of the disease phenotype and the age at diagnosis. We saw different clinical presentations depending on when telomeres reached a critical threshold, said lead author Jonathan Alder, PhD, now an assistant professor of medicine at the University of Pittsburgh. Crucially, the Johns Hopkins team reported that telomere measurements led to treatment changes in one-quarter of 38 pediatric and adult patients with idiopathic bone marrow failure as physicians changed to less harsh therapies like reduced doses of chemotherapy and less use of immunosuppressant drugs.

Patnaik and his colleagues also use telomere testing to assess patients with bone marrow failure, as part of Mayo Clinics Center for Individualized Medicine. We found very quickly that the most common referrals to the Center were people with short telomere syndromes that extended beyond bone marrow failure into conditions like lung and liver fibrosis, he said. In recent reports, he and his team have described their diagnostic workups for patients with suspected inherited STS and with unexplained cytopenias. In the case of inherited STS, they defined this population as having telomere lengths in either granulocytes or lymphocytes less than the first centile of normal controls (Mayo Clin Proc 2018;93:834-9). They perform this screening in concert with an in-house next-generation-sequencing (NGS) panel that consists of telomere-associated genes. Patients who test negative for the NGS panel proceed to research-based whole-exome sequencing to identify other potential mutations.

The options for measuring telomere length are broadand complicated. We are measuring a population of cells, and each cell has between 92 and 184 telomeres, so we are really measuring a population of telomere lengths in an individual, said Alder. Some methods measure individual telomere length, some measure the average, some measure the average of many cells together, and still others measure the average of individual cells.

These methodologies encompass quantitative polymerase chain reaction (qPCR), fluorescence in situ hybridization (FISH)-based techniquesincluding flow cytometry combined with FISH (flow-FISH) and quantitative FISHtelomere restriction fragment length analysis, optical techniques, and hybridization protection assays. In hospital settings, the preferred method is flow-FISH, which both Johns Hopkins and Mayo Clinic use. Both favor this approach because of its accuracy, reproducibility, ability to define normal telomere length range, and ability to test large numbers of samples. Flow-FISH is standardized, clinically validated, cost-effective, commercially available, and can be implemented anywhere to screen patients with suboptimal telomere length, said Patnaik. Flow-FISH reports also provide data on telomere lengths relative to age, which is important because telomere attrition is part of the normal aging process.

Although an estimated 5,000 to 10,000 individuals in the U.S. have STS, the place for telomere testing remains unclear in diagnosing and predicting long telomere-associated cancers. In cancers where telomere length is elongated, the role of telomere-related testing is still ongoing and not quite ready for clinical prime time, said Patnaik. He added that more research into understanding why shorter telomeres negatively impact outcomes in the management of bone marrow failure syndromes and blood cancers will be quite useful, potentially informing future clinical interventions.

Others remain skeptical about how broadly telomere testing might disseminate. Telomere length testing makes complete sense for rare diseases like STS where you have a specific genetic cause. But I dont think it has any clinical relevance as yet for identifying risk factors for more common diseases like cancer, cardiovascular disease, diabetes, chronic lung disease, Alzheimers disease, and infectious diseases, said Brge Nordestgaard, MD, professor of clinical medicine at the University of Copenhagen and chief physician in the department of clinical biochemistry at Herlev and Gentofte Hospital and Copenhagen University Hospital Denmark. Nordestgaard has conducted genetic epidemiology studies exploring long telomere length and cancer risk and short telomere length and ischemic heart disease risk.

Alder agreed that work remains in identifying the best diagnostic niches for this emerging field. Telomere testing is definitely not a standard part of every clinical work-up in the nation. In the future, it is important to define clinical scenarios where it makes sense for telomeres to be measured, he said. The next step would be to define what the critical thresholds are for making a diagnosis that can lead to an actionable intervention.

Even as the science and practice of telomere testing remains in flux, Armanios, speaking at a Pulmonary Fibrosis Foundation meeting, laid out a future in which genetic evaluation with telomere length might replace lung biopsies in affected patients. She also envisions a time when identifying patients with telomere-mediated lung disease could aid in managing lung transplants, both for anticipating and averting complications.

One catch in advancing the field is that there are no specific treatments for telomere biology disorders. Patnaik echoed Armanios call for specialty-crossing care to plot next steps for newly diagnosed patients. More centers of excellence are needed that can integrate different clinical fields and provide a unique multidisciplinary skill set to manage and counsel these patients, he stressed.

Pranali P. Pathare, PhD, is a medical writer and editor in St. Louis. +Email: ppranali@gmail.com

Continued here:
On the Trail of Telomeres - American Association for Clinical Chemistry (AACC)