Category Archives: Human Genetics

Sergi Beltran and Leslie Matalonga pictured in front of a supercomputer and servers that hosts the RD-Connect GPAP platform. The platform is located at the CNAG-CRG facilities in the Parc Cientific de Barcelona. Credit: Centro Nacional de Anlisis Genmico (CNAG-CRG)

Rare disease experts detail the first results of an unprecedented collaboration to diagnose people living with unsolved cases of rare diseases across Europe. The findings are published today in a series of six papers in theEuropean Journal of Human Genetics.

In the main publication, an international consortium, known as Solve-RD, explains how the periodic reanalysis of genomic and phenotypic information from people living with a rare disease can boost the chance of diagnosis when combined with data sharing across European borders on a massive scale. Using this new approach, a preliminary reanalysis of data from 8,393 individuals resulted in 255 new diagnoses, some with atypical manifestations of known diseases.

A complementary study describes the method in more detail and four accompanying case studies showcase the advantages of the approach. In one case study, researchers used the method to identify a new genetic form of pontocerebellar hypoplasia type 1 (PCH1), a genetic disease that affects the development of the brain. PCH1 is normally linked to mutations in four known genes. The researchers used the method to identify a new variant in a fifth gene.

In another case study, researchers used the method on an individual with a complex neurodevelopmental disorder and found the disease was caused by a new genetic variant in mitochondrial DNA. This went previously undetected because the patient did not present typical symptoms of a mitochondrial disorder. The diagnosis will help tailor treatment for the individual, as well as inform their family members on the possibility of passing it on to future generations.

Key to the reanalysis of unsolved cases is theRD-Connect Genome-Phenome Analysis Platform, which is developed, hosted and coordinated by the Centro Nacional de Analisis Genomico (CNAG-CRG), part of the Centre for Genomic Regulation (CRG), based in Barcelona.

Recognized officially by the International Rare Diseases Research Consortium and funded by the EU, Spanish and Catalan governments, the RD-Connect GPAP provides authorised clinicians and researchers with secure and controlled access to pseudonymized genomic data and clinical information from patients with rare diseases. The platform enables the secure, fast and cost-effective automated re-analysis of the thousands of undiagnosed patients and relatives entering the Solve-RD project.

According to Sergi Beltran, co-leader of Solve-RD data analysis and Head of the Bioinformatics Unit at CNAG-CRG, Solve-RD has shown that it is possible to securely share large amounts of genomics data internationally for the benefit of the patients. The work we are publishing today is just the tip of the iceberg, since many more patients are being diagnosed thanks to the innovative methods developed and applied within Solve-RD.

An estimated 30 million people in Europe are affected by a rare disease during their lifetime. More than 70% of rare diseases have a genetic cause. However, around 50% of patients with a rare disease remain undiagnosed even in advanced expert clinical settings that use techniques such as genome sequencing.

At the same time, scientists around the world are finding an average of 250 new gene-disease associations and 9,200 variant-disease associations per year. As scientific understanding expands, reanalyzing data periodically can help people receive a diagnosis.

The consortium, which consists of more than 300 researchers and clinicians in fifteen countries, and who collectively see more than 270,000 rare disease patients each year, aims to eventually diagnose more than 19,000 unsolved cases of rare diseases with an unknown molecular cause. Their preliminary findings are an important first step for the development of a European-wide system to facilitate the diagnosis rare diseases, which can be a long and arduous process.

About Solve-RD

Solve-RD solving the unsolved rare diseases is a research project funded by the European Commission for five years (2018-2022). The consortium, which consists of 21 European academic institutions and 1 academic partner from the United States, is jointly coordinated by the University of Tbingen in Germany, Radboud University Medical Centre in the Netherlands and the University of Leicester in the UK. The Centro Nacional de Anlisis Genmico (CNAG-CRG) in Barcelona is the main partner in Spain.

About CNAG-CRG

The Centro Nacional de Anlisis Genmico is one of the largest European centers in terms of sequencing capacity. It was created in 2009 with the mission to carry out projects in nucleic acid analysis in collaboration with the national and international research community. It is a non-profit organization funded by the Spanish Ministry of Economy and Competitiveness, and the Catalan Government through the Economy and Knowledge Department and the Health Department. Since 2015 it is part of the Centre for Genomic Regulation (CRG).

The center focuses on sequencing and analysis projects in areas such as cancer genetics, rare disorders, host-pathogen interactions, de novo assembly and genome annotation, evolutionary studies and improvement of species of agricultural interest, in collaboration with universities, hospitals, research centers and companies in the sector of biotechnology and pharma.

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Unprecedented Data Sharing Drives New Rare Disease Diagnoses Just Tip of the Iceberg - SciTechDaily

To analyze the genome or the genetic characteristics of a living organism, scientists typically rely on samples of millions of cells. The problem is that the DNA in each of our cells is not identical.

Until recently, the amount of DNA that could be extracted from a single cell couldnt provide enough material for genetic analysis, but advances in single-cell genomics could be the key to solving some of the mysteries of diseases like cancer, which is the result of damage to individual cells. It could also help researchers better understand complex bodily systems like the brain and the immune system that are composed of a variety of cell types, each with their own unique genetic characteristics.

As a means to solving the problems posed by single-cell genomics, a process called whole-gene amplification is providing researchers with ways to generate sufficient quantities of DNA necessary for analysis by replicating the genetic material extracted from each cell. The process is not without its challenges, but a paper by Shiwei Liu, a Ph.D. candidate in biology in the University of Virginias College of Arts & Sciences; UVA biology professor Jennifer L. Gler; and others, published recently in the journal Genome Medicine, outlines an approach to whole-genome amplification resulting from a collaboration with neuroscientists in UVAs School of Medicine that could provide an effective framework for creating new and more effective treatments for a variety of diseases.

Gler and Liu study the single-celled protozoan parasite, called Plasmodium, that causes malaria, a disease that kills nearly half a million people every year. There are no effective vaccines in widespread use for the disease, and one of the problems the medical community faces is that the organism can rapidly develop resistance to the drugs that have been developed to wipe it out. Glers team has been working to understand cellular mechanisms that allow it to survive and how genetic diversity within the parasite population affects its resistance to drugs.

If you take them on a single-cell level, we start to appreciate that individual cells in a population of cells actually have small differences, and those small differences might not be noticeable, but they can have an impact if they disrupt how drugs or other treatments work, Gler said.

In recent years, scientists have been finding ways to capture and extract DNA from single cells, which makes it possible to identify the small but critical differences between individual cells. However, the process requires a series of steps that create additional problems for researchers attempting to amplify the DNA, a process that involves reproducing enough identical copies of that DNA to be able to identify, or sequence, its component parts. The amplification process is especially challenging for malaria researchers.

The genome of the malaria parasite is really small, almost 300 times smaller than the human genome, so if we capture one genome from the malaria parasite, were starting at a much lower level than we need to be able sequence it, so we have to use a really sensitive, highly specific method to be able to amplify it, Gler explained. Then you sequence it, and presumably everything in that sequence of all those different copies is going to reflect that first genome, and this is where a big challenge comes in. When you make those many copies, you introduce errors, and you cant always assume that those many copies reflect the initial genome. Thats been a big problem in single-cell genomics.

Because the Plasmodium parasite lives in the human bloodstream, Gler and her team also needed a method that would allow them to preferentially amplify the genome of the protozoan over its host, a problem that is unique to studying organisms that live inside the cells of other organisms.

The solution came as the result of a collaboration with Mike McConnell, a neuroscientist who works as an investigator at the Lieber Institute for Brain Development Maltz Research Laboratories in Baltimore. Gler met McConnell when he worked in the UVA School of Medicines Department of Biochemistry and Molecular Genetics.

McConnell specializes in single-cell genome analysis for human brain cells and had already developed strategies for capturing single cells. He had also worked with Ian Burbulis, an assistant professor of biochemistry and molecular genetics at UVA, to use a method called multiple annealing and looping based amplification cycles, or MALBAC, to solve some of the problems inherent in the process of single-cell genome amplification.

Gler recognized the similarities in the challenges they were facing, and her team was able to use McConnells method for capturing single cells and was also able to adapt the MALBAC method for use in reproducing the Plasmodium DNA accurately while limiting the contamination that can be caused by its hosts DNA.

The collaboration with Mike McConnells lab helped build the basis for our single-cell sequencing project. They not only provided the original standard protocol of the whole genome amplification method called MALBAC, but they also offered instructions to conduct the essential steps of the single-cell sequencing pipeline, including single-cell isolation, whole- genome amplification and data analysis, Liu said.

We had worked out all of the molecular biology steps, the enzymes to use and how to analyze it and that sort of thing, and we made some improvements to make it better, and Jenny was able to start there, McConnell said. He gave credit to Gler and Liu for seeing the potential that his research offered.

Jenny and Shiwei did the heavy lifting to take what we had done and make it work for malaria, McConnell said.

I think our collaboration with his lab from the very beginning of his project was absolutely instrumental because we could go to his lab and learn what they were doing instead of starting from ground zero, so we started at a much higher level, Gler said. It was a team effort that ended up being very successful because we had that head start.

A lot of this single-cell technology is really focused on human cells, and thats great; we want to learn more about human health, Gler said. But when you have these microbes or other organisms that have more challenging genomes, we need to be able to apply these methods to those genomes, too. This is one of the first studies to suggest that we can overcome those challenges.

Its a start for us to understand the biology of the malaria parasite, but its also a start for understanding other organisms with challenging genomes.

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New Approach to DNA Research Could Be Key to Solving Mysteries of Deadly Diseases - University of Virginia

Outside the Sheldon Chumir safe injection site in Calgary, Alberta, on May 31, 2019.

Todd Korol/The Globe and Mail

Calgary residents Emily Doerksen and Tianna Cleveland organized a protest scheduled for Friday night to protect Safeworks, the citys only supervised drug consumption site, located at the Sheldon M. Chumir Health Centre in the citys Beltline neighbourhood a site the provincial government plans to shut down four years after it opened.

The province said the clinic will remain open until it is replaced with two other supervised consumption sites at locations that already serve individuals dealing with addiction, though no details have been released about where they will be placed.

With the closure of the Calgary site, Ms. Doerksen worries people who use its services may lose trust in the system, and said she feels the province doesnt recognize safe consumption sites as essential, life-saving social services.

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Its not about just offering people a place to do drugs, said Ms. Doerksen, who is working on a masters degree at McGill University focusing on human genetics and bioethics. Its offering them a community and a sense of safety.

On Wednesday, the province announced new regulations for supervised consumption sites, including standardized data collection, clinical practice standards, staff qualifications and training, physical site requirements and good neighbour agreements. Service providers must also tell clients about treatment options, pathways to detox and recovery services.

The United Conservative Party government targeted supervised consumption services, or SCS, in its 2019 election campaign with a promise to ensure they are linked to treatment and to review negative effects of such facilities.

The government struck a panel to review the sites. A report released last year concluded that supervised consumption sites increase crime and disorder in neighbourhoods that host them, though the report was widely criticized by public-health experts.

Due to COVID-19, low attendance at supervised drug consumption site in Calgary may increase risk of overdoses

Supervised consumption services face host of difficulties in Prairie provinces

Experts say supervised consumption sites are critical to reducing overdose-related deaths, and additional regulations will make it more difficult to open and run such sites, as well as limit who has access to them.

Data released this week show that in the first quarter of 2021, there were 346 fatal opioid deaths in Alberta an average of nearly four per day and more than double the number of deaths in the same months last year. The COVID-19 pandemic has coincided with significant increases in fatal opioid overdoses in Alberta and elsewhere in Canada.

In a news release, the provincial government said the new mandatory quality standards the first of their kind in the country will improve community safety, provide higher-quality services and increase integration with the health care system.

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Hakique Virani, an associate clinical professor of public health and addictions medicine specialist at the University of Alberta, said these new regulations paint an erroneous picture about the state of SCS in the province.

To add more layers at a time when were in an epidemic of fatal overdoses seems, at least, misguided, he said.

Justin Marshall, press secretary for the associate minister of mental health and addictions, Jason Luan, said collecting personal data such as health-card numbers will integrate clients to the health care system. but Dr. Virani disagrees.

He said requiring identification will reduce access for the most vulnerable clients, referencing University of Alberta research that found only 36 per cent of respondents would use SCS if identification was needed.

Elaine Hyshka, one of the researchers in the University of Alberta study, said clients using SCS are hesitant to release their identification in fear of arrest and medical discrimination that may follow if their records show they used drugs.

Dr. Virani said another area of concern is the requirement for SCS staff to undergo background checks, which could prevent them from working in the sector. Peer support workers have life experience that is invaluable, he said.

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NDP critic Lori Sigurdson said Alberta is in the middle of a crisis, noting that instead of expanding services, the province will further alienate people who need access to SCS.

The government needs to meet people where theyre at before they may be willing to undergo treatment, she noted.

Many people are dying a preventable death.

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Critics of Alberta's new rules for supervised consumption sites say they will curb access for vulnerable clients - The Globe and Mail

Twenty years ago, President Bill Clinton announced completion of what was arguably one of the greatest advances of the modern era: the first draft sequence of the human genome.

"Without a doubt, this is the most important, the most wondrous map ever produced by humankind," Clinton said on June 26, 2000 from the White House, predicting that genome science "will revolutionize the diagnosis, prevention and treatment of most, if not all, human diseases." In the future, he said, "doctors will increasingly be able to cure diseases like Alzheimer's, Parkinson's, diabetes, and cancer by attacking their genetic roots."

And indeed, the sequencing of the human genome achieved simultaneously by the Human Genome Project (HGP), an international consortium begun in 1990 and led by Francis Collins, MD, then director of the National Human Genome Research Institute, and by J. Craig Venter, PhD, with his team at the privately held Celera Genomics has revolutionized the approach to human health.

President Bill Clinton is flanked by Dr J. Craig Venter (left) and Dr Francis Collins announcing the first draft sequence of the human genome in June 2000.

Although the unbridled optimism of 20 years ago has not been matched with success in every quarter, much of the promise has begun to be realized. Scientists have so far identified 5000 rare diseases and 40 to 50 genes that confer cancer risk, developed simple prenatal blood tests to detect chromosomal abnormalities, and generated genetic profiles of tumors to facilitate better-targeted therapies, among other accomplishments. Even the current global fight against COVID-19 is relying on genomics.

"There hasn't been a pharmaceutical developed in last 20 years that hasn't utilized genome information," Venter told Medscape Medical News.

"Not a day goes by in science that we don't see some offshoot of benefit from what happened 20 years ago," said Eric Topol, MD, the chair of innovative medicine at Scripps Research in La Jolla, California, and Editor-in-Chief of Medscape.

Finding the genes was just the beginning though; describing function and using that information therapeutically is still just getting underway in many clinical areas. "We now know that genes are only a small fraction of the complexity of the human genome," says Eric Green, MD, PhD, the current director of the National Human Genome Research Institute (NHGRI).

When it started, the sequencing of the human genome did not seem like a value proposition nor was it expected to be. Congress authorized $3 billion for the HGP in 1990 and set a target completion date of 2005.

The final sequence, a database of some 3 billion DNA base pairs, came in under budget the NHGRI estimates the cost at $2.7 billion in 2003, two years ahead of schedule and exactly 50 years after James Watson and Francis Crick first described DNA.

It had been only 15 months since the international consortium of 1000 researchers across six nations began their sequencing effort in earnest, and a scant 9 months from when Venter's team starting sequencing its human genome. Celera Genomics spent just $100 million, Venter estimates.

What seemed like a massive investment at the time now looks like chicken scratch. "It was a bargain," Topol said.

The race to create the map of the human genome would generate goodwill, create strife, elevate egos, and make careers. Much has been written about the clash between Collins and Venter two polar opposites with different motivations and different approaches.

Collins, a dedicated public servant and man of deep Christian faith, believed in the power of the academic and governmental research enterprise.

Venter, on the other hand, ruffled feathers with his big ideas and generally more capitalistic approach. He began his career at the National Institutes of Health (NIH) in 1984 and created a gene discovery tool called expressed sequence tags (ESTs). That caught the eye of venture capitalists, who lured him out of the agency. They backed Venter's nonprofit, The Institute for Genomic Research (TIGR), to develop the technology.

At TIGR, Venter decoded the genome of Haemophilus influenzae using his whole genome "shotgun" technique. When he applied to the NIH for a grant to support the shotgun method, however, he was rejected. The maker of a DNA sequencing machine, PE Biosystems, then installed Venter as the CEO of the new, private Celera Genomics in 1998.

The NIH-led consortium did not see the value of the shotgun approach and instead relied on a more traditional sequencing method, which was more laborious and time-consuming, Topol recalls. After that NIH rejection, the competition was on, and the rivalry became bitter.

"There was no love lost between these two gentleman," Topol acknowledged. On that day in June 2000 when the announcement was made, "it required Clinton and whoever else to kind of get them to stand together and make nice," added Topol, who was present at the celebration.

A release from the NIH on the commemoration of the 20th anniversary in June of this year describes the situation this way: "The joint presence of these two scientific leaders signified the agreed-upon shared success of the public HGP and private Celera Genomics efforts in generating the first draft sequence of the human genome."

Still, the competition, in retrospect, was a good thing because it accelerated progress, Topol said.

The draft sequence unveiled in 2000 covered 90% of the genome at an error rate of one in 1000 base pairs, but there were more than 150,000 gaps, and only 28% of the genome had reached true completion. When the final version was made public in 2003, there were less than 400 gaps and 99% of the genome was finished with an accuracy rate of less than one error in every 10,000 base pairs.

Looking back, the technologies used then "now seem almost prehistoric," says NHGRI director Green. "Nothing in the way we sequence DNA is the same now. We can do it in a day or two and it costs less than a thousand dollars." He expects the cost of sequencing a human genome will eventually drop below $100.

The final, almost-complete sequence published in 2003 was "foundational," providing "the alphabet around which everything else has been constructed," said Mark McCarthy, MD, senior director and staff scientist in human genetics at the California-based biotechnology company, Genentech. "It's hard to think of a more concrete example in science other than maybe the periodic table," McCarthy told Medscape Medical News.

Doing genetic research before the full sequence was published, he says, was like being an "explorer in some novel land." Without a clear map of the terrain, researchers used analogue methods to try to determine locations of genes or recombination events, he said. It was frustrating and "a huge impediment to progress."

Now, scientists can "just click on a mouse and get almost immediately the worlds of data around any genomic regions," he said.

"Most scientists today never had to sequence a gene," Venter points out. "They don't have to, because they just look it up on the internet."

"Graduate students today can't imagine how we ever did any experiments or learned anything without having access to the human genome sequence with a click of a mouse," said Collins, in a video testimonial celebrating the 30th anniversary of the start of the project.

To Collins, one of the genome project's main goals was to give clinicians better tools to heal their patients. "Together we must develop the advances in medicine, that is the real reason for doing this work," he said in 2000.

If you would have told me that in my professional career I would have seen genomics actually change the practice of medicine in any way, shape, or form, I would have said, 'There's just no way, we're two generations away from that.' Dr Eric Green, director of the National Human Genome Research Institute

But it wasn't until a decade later that genomics was talked about in medicine, said Green. "Now, we have clear examples for genomics being used every day," he said.

"If you would have told me that in my professional career I would have seen genomics actually change the practice of medicine in any way, shape or form, I would have said, 'There's just no way, we're two generations away from that,'" Green said.

Perhaps the biggest impact of these advances in genomics to date has been in the practice of oncology.

"Cancer care has been one of the biggest beneficiaries of the genomic revolution," said Frederick M. Schnell, MD, chief medical officer of the Community Oncology Alliance (COA). Schnell points to the work of Brian Druker, MD, who helped discover the mutation that causes chronic myelogenous leukemia and also was instrumental in developing a precision treatment for CML, imatinib (Gleevec).

"That was probably the singular most important development for a particular, albeit not common, but not uncommon disease that had a disgraceful, horrible projected survival and mortality associated with it, and has changed it to a curable disease," Schnell told Medscape.

The HGP led to the Cancer Genome Atlas, a book of some 20,000 cancer genomes and matched normal samples spanning 33 cancer types.

"In order to understand what was going wrong in a cancer, you first had to understand what the genome was supposed to look like in somebody the cell that was not cancerous," said Richard Schilsky, MD, chief medical officer and executive vice president of the American Society of Clinical Oncology (ASCO).

The comparisons "help us identify mutations that are real drivers of cancer and have opened up the whole field of precision oncology," Schilsky, formerly chief of hematology/oncology and deputy director of the University of Chicago Comprehensive Cancer Center, told Medscape Medical News.

In addition to helping identify cancer susceptibility genes, the genome project also led to variations associated with how drugs are metabolized, Schilsky said.

For instance, it is now known that 10% of the population has a variant of the UGT1A1 gene that leads to poor metabolism of the chemotherapy drug irinotecan (Camptosar), causing worse side effects. The drug's label now notes the availability of a simple lab test to look for the variant.

Schilsky is lead investigator of an ASCO-sponsored trial called TAPUR that aims to match patients with certain tumor variants to therapies that might work, but are not FDA-approved for that particular cancer. Some 2000 individuals have enrolled and received free medications (provided by one of the eight drug companies participating) since the trial began in 2016, said Schilsky.

One goal is to collect evidence on off-label uses which might help therapies gain acceptance in clinical practice guidelines and, potentially, reimbursement. TAPUR also aims to help oncologists learn more about genomics.

Precision oncology is still not available to all cancer patients, however. Schnell said the COA is lobbying for better access and insurance coverage.

He believes that genomics could be used as a replacement for screening tests such as mammograms and colonoscopies. "This is going to be a big application point for the genomic revolution as it continues," he said.

Topol agrees that genomics could create a tailored approach to prevention. "Why does every woman need a mammogram when only 12% will ever develop breast cancer?" he says.

The progress made to date in understanding the human genome is also proving to be a key weapon as scientists fight the important current threat of the COVID-19 pandemic.

China made the first genetic sequence of the SARS-CoV-2 virus available on January 12, 2020, just weeks after the nation reported the initial cluster of cases.

Researchers have since uploaded 245,000 genomic sequences of the SARS-CoV-2 virus to the World Health Organization's Global Initiative on Sharing All Influenza Data (GISAID) portal. The speedy sequencing and widespread sharing of data led to quick development of molecular diagnostics and identification of potential targets for vaccines and therapeutics.

The NHGRI, among others, is supporting genomic studies around the world that aim to understand the differences between those who become severely ill and those "who barely seem to notice they have the disease," NHGRI director Green told Medscape Medical News. "There is no question there is going to be some genomic basis for the severity of the disease,"

He also expects genomics to be used in vaccine trials to separate responders from nonresponders.

While rare monogenic diseases were a relative cinch, common illnesses like hypertension, diabetes, and Alzheimer's disease have turned out to be more complicated.

It wasn't until the mid-2000s, when genome-wide association studies (which look for small variations that occur more frequently in people with disease) came into greater use, that scientists began to get a clearer picture, said Genentech's McCarthy.

It turns out that "hundreds, if not thousands of genetic variations and genetic regions" seem to predispose someone to a common disease, he said. He's applying genome-wide approaches in type 2 diabetes, but it requires datasets of a million or more people to get a robust result, McCarthy said.

Even then, "it just gives you a bunch of sign posts around the genome and then you have to work out what they do and how they influence predisposition in a given individual," he said. Researchers have begun to understand "the range of pathways and networks that are involved in the genetic predisposition to type 2 diabetes," which in turn is giving information on potential therapeutic targets.

The obstacle is not having enough genome-wide genetic data, which may change as more countries find ways to collect more genetic data, McCarthy said.

"We're not getting complete comprehensive views of all the genes involved and all the genomic variants that confer risk," for chronic diseases, agreed Green. "That's the big challenge for the next decade."

Another challenge that NHGRI has outlined in its strategic plan, released in October, is broadening human genome reference databases to include a wider representation of humanity. "Much like all other scientific disciplines, genomics is reckoning with systematic injustice and biases of the past," the agency said in a press release. The plan also addresses data control, privacy, genome editing, and barriers to a thriving genomics enterprise.

Venter believes that getting to the root of chronic diseases means combining the phenotype with the genotype. In 2013, he started Human Longevity, a company that offers sequencing, imaging, and a host of diagnostics to those who can afford the service, to give a complete picture.

"Without extensive phenotype information, the genome isn't highly useful on its own," said Venter, who feels the combination could be a true preventive medicine platform.

As much as the sequencing of the genome has brought to medicine, "I think the greatest promise of the genome remains to be realized," said Venter.

The initial focus was on genes. Humans, it turns out, have only 20,000 genes, not that many more than worms or fruit flies. But there's more to life outside of those genes, said Green.

The human genome "is a treasure chest, but we have only gotten a limited number of the keys so far," said Topol. "It is not nearly as informative as it could be."

And genomics still has the potential to do harm an issue that gets periodic scrutiny by commissions and the public. On that day in 2000 at the White House, Venter noted that a just-released poll had reported that 46% of Americans believed that "the impact of the Human Genome Project will be negative."

Privacy of genetic information is a perennial concern, and technologies such as gene editing, which allows scientists to alter DNA have brought up new ethical challenges.

On the other hand, the public has been mesmerized by genetic genealogy technologies that allow them to determine their own ancestry or disease risk, and that have more recently helped law enforcement solve crimes, some of them longstanding cold cases.

Twenty years ago, Venter predicted that the wonders would continue unabated. "The complexities and wonder of how the inanimate chemicals that are our genetic code give rise to the imponderables of the human spirit should keep poets and philosophers inspired for the millenniums," he said in 2000.

His view is more tempered today. "I'm optimistic about the future," says Venter now. "I'm pessimistic about how soon it will get here."

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The 'Wondrous Map': Charting of the Human Genome, 20 Years Later - Medscape

SOUTH SAN FRANCISCO, Calif., Dec. 16, 2020 /PRNewswire/ --Neuron23Inc., an early stage biotechnology company focused on developing precision medicines for genetically defined neurological and immunological diseases, today announced its launch backed by a combined $113.5 million Series A and B financing. The funding was comprised of $33.5 million Series A financing from Westlake Village BioPartners and Kleiner Perkins, and $80 million Series B financing led by Redmile Group. Additional Series B investors included Westlake Village BioPartners, Kleiner Perkins, Cowen Healthcare Investments, Acorn Bioventures, HBM Partners, Perceptive Advisors, and Surveyor Capital (a Citadel company). Neuron23 was founded through an innovative partnership with German biotechnology company, Origenis GmbH.

Proceeds from the financing will be used to accelerate the development of Neuron23's pipeline and expand its state-of-the-art artificial intelligence (AI)-enabled drug discovery and biomarker platforms for identifying therapeutics for devastating neurodegenerative diseases including Parkinson's disease, neuroinflammatory diseases such as multiple sclerosis, and systemic autoimmune and inflammatory diseases. Specifically, the round will allow the company to advance two-to-three existing development candidates into the clinic in the next 24 months, and to bolster its platform to identify genetic signatures of patients most likely to respond to the development candidates. Within each program, the potential exists to address multiple central nervous system (CNS) and systemic diseases, creating "pipeline within a product" opportunities. Proceeds from the financing will also support talent recruitment, technology development, and intellectual property (IP) expansion and protection.

"We are pleased to have such strong support from this syndicate of blue-chip investors who recognize our potential to build a new type of precision medicine company," said Nancy Stagliano, PhD, CEO and Board Chair, Neuron23. "Neuron23's approach can revolutionize how we treat genetically defined neurological and inflammatory diseases, thus significantly improving patients' lives. Our team of accomplished entrepreneurs, scientists, and clinicians, with significant experience in drug discovery and development, is poised to harness the latest technologies in AI, human genetics, and medicinal chemistry to streamline the delivery of the right medicines to both genetically defined patients and the broader group."

Neuron23 is advancing multiple therapeutics addressing genetically validated targets, with lead programs against leucine-rich repeat kinase 2 (LRRK2), a gene associated with Parkinson's disease and systemic inflammatory diseases, and tyrosine kinase 2 (TYK2), a JAK family protein that plays a role in pathological immune signaling. The prioritization of LRRK2 and TYK2 allows the company to spotlight its foundational strengths in chemistry, biology, human genetics, and AI.

Beth Seidenberg, MD, co-founding managing director of Westlake Village BioPartners and a partner at Kleiner Perkins, led the Series A round and participated in the Series B round.

"Neuron23 has tremendous potential to usher in the next step-change in treating genetically defined neurological and immunological diseases, and the caliber of the investors in our syndicate speaks to the excitement around Neuron23 and its future," Dr. Seidenberg said. "Dr. Stagliano brings significant expertise in neuroscience and a proven ability building high-performing companies, having previously served as CEO of True North Therapeutics, iPierian, and CytomX Therapeutics. With Dr. Stagliano at the helm, we are well positioned for a number of financing scenarios in the future, including additional private capital, accessing the public markets, or partnering with Big Pharma."

Neuron23 has been working in stealth mode since its founding in October 2018 by neurogeneticist and Chief Business Officer Adam Knight, PhD, along with Origenis GmbH, and Kleiner Perkins.

"Our partnership with Origenis gives us significant competitive advantages over traditional drug discovery approaches, including high throughput capabilities to identify scores of potent, selective, and brain-penetrant molecules for each target," said Dr. Knight.

In connection with the Series A and B rounds, Beth Seidenberg, Amrit Nagpal (Redmile Group), Kevin Raidy (Cowen Healthcare Investments), Michael Almstetter (Origenis), and Nancy Stagliano serve on the Board of Directors.

Westlake Village BioPartners recently launched two funds totaling $500 million and launched a new biopharma company, ACELYRIN. Westlake's investment in the Series B round for Neuron23 came from its Opportunity 1 fund, one of the new funds launched and designed to invest additional capital into companies they incubated that show promise. "We are doubling down on Neuron23," added Dr. Seidenberg.

About Neuron23

Neuron23Inc. is an early stage biotechnology company focused on developing precision medicines for genetically defined neurological and immunological diseases. Neuron23 leverages recent advances in human genetics, combined with their state-of-the-art artificial intelligence (AI)-enabled drug discovery and biomarker platforms, to advance therapeutics for devastating diseases. The Company's focus areas are neurodegenerative diseases, neuroinflammatory diseases, and systemic autoimmune and inflammatory diseases. Founded in 2018, Neuron23 has assembled a world-class team of experts and entrepreneurs located in South San Francisco, CA, and Munich, Germany. For more information, please visit http://www.neuron23.com.

About Origenis GmbH

Origenis GmbH is a privately held German biopharmaceutical company developing brain-penetrating highly selective small molecule medicines and diagnostics for a variety of neurodegenerative and neuroinflammatory diseases. Origenis leverages its unique capabilities in drug design, compound synthesis, and characterization to engineer a continuous stream of proprietary intellectual property (IP)-protected new chemical entities capable of permeating the blood-brain barrier. Origenis' approach has been validated by multiple partners resulting in a significant IP and R&D portfolio that ensures strong patent protection. For more information, visitwww.origenis.com.

About Westlake Village BioPartners

Westlake Village BioPartners is a Los Angeles area-based venture capital firm focused on incubating and building life sciences companies with entrepreneurs who have the potential to bring transformative therapies and technologies to patients. Westlake manages more early stage venture capital solely from the greater Los Angeles area than any other firm. The Westlake model is built on the founding team's unique experience in successfully identifying and developing breakthrough therapies and building organizations, based on their extensive R&D experience. For more information, please visitwww.westlakebio.com.

SOURCE Neuron23

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Neuron23 Closes $113.5 Million Series A and B Financing led by Westlake Village BioPartners, Kleiner Perkins, and Redmile Group - PRNewswire

MENLO PARK, Calif., Dec. 14, 2020 (GLOBE NEWSWIRE) -- Pacific Biosciences of California, Inc. (Nasdaq:PACB), a leading provider of high-quality sequencing of genomes, transcriptomes and epigenomes, today announced that three of the United Kingdoms leading core laboratories have increased their investment in the companys Single Molecule, Real-Time (SMRT) Sequencing technology. Edinburgh Genomics, Oxford Genomics Centre, and University of Liverpool Centre for Genomic Research have each added Sequel II or Sequel IIe Systems to expand the delivery of highly accurate long-read sequencing services to researchers worldwide.

PacBio supports sequencing labs around the world and we are pleased to expand our collaboration with these important partners in the United Kingdom who share our commitment to providing scientists with the most advanced research technologies, said Chris Seipert, Vice President of Sales and Support at PacBio. PacBio HiFi sequencing is enabling scientists to unlock discoveries across a number of important research applications including variant detection and de novo assembly, among others. We look forward to working with our worldwide collaborators to make HiFi sequencing available to anyone seeking industry-leading accuracy and completeness in one easy-to-use technology.

"The Oxford Genomics Centre, the Core Facility of the Wellcome Centre for Human Genetics, is excited to invest in the PacBio Sequel IIe, introducing their highly-accurate long-read sequencing to Oxford and beyond, said David Buck, PhD, Head of High-Throughput Genomics at the Oxford Genomics Centre. This advance will drive new developments in analyses from whole viral and microbiomesequences to complete assemblies of complex structural regions of the human genome and their epigenetic footprints."

The PacBio Sequel II and Sequel IIe Systems provide scientists with access to high throughput, cost-effective, highly accurate long-read sequencing. The recently launched Sequel IIe System features hardware and software improvements that enable users to work directly with HiFi reads, the most valuable and informative sequencing data currently available. HiFi reads combine the accuracy of Sanger sequencing (>99.9%) with long reads (up to 25 kb). Together, the length and accuracy of HiFi reads make them ideal for de novo genome assembly, detection of variants from single nucleotide changes to large structural variants, and other genomic or transcriptomic investigations.

In addition to highly accurate long-reads, HiFi sequencing offers our research customers many important advantages including easy library preparation, low coverage requirements, small file sizes, and fast assembly, said Javier Santoyo-Lopez, PhD, Service Manager at Edinburgh Genomics, School of Biological Sciences, University of Edinburgh.

Steve Paterson, PhD, Professor of Genetics and Director of the Centre for Genomic Research & NERC Environmental Omics Facility, University of Liverpool commented: We are excited to have two PacBio Sequel II Systems that we can offer to UK researchers. They will give us the power to look at the richness of genomes across species and to help develop new treatments against microbial infections.

For more information about the PacBio Certified Service Provider Program, please visit http://www.pacb.com/CSP.

About Pacific BiosciencesPacific Biosciences of California, Inc. (NASDAQ: PACB), is empowering life scientists with highly accurate long-read sequencing. The companys innovative instruments are based on Single Molecule, Real-Time (SMRT) Sequencing technology, which delivers a comprehensive view of genomes, transcriptomes, and epigenomes, enabling access to the full spectrum of genetic variation in any organism. Cited in thousands of peer-reviewed publications, PacBio sequencing systems are in use by scientists around the world to drive discovery in human biomedical research, plant and animal sciences, and microbiology. For more information please visit http://www.pacb.com and follow @PacBio.

PacBio products are provided for Research Use Only. Not for use in diagnostic procedures.

Forward-Looking StatementsAll statements in this press release that are not historical are forward-looking statements, including, among other things, statements relating to market leadership, uses, accuracy, quality or performance of, or benefits of using, our products or technologies, including SMRT sequencing technology, the expected benefits, suitability or utility of our methods, products or technologies for particular applications or projects, the ability of the Company to be successful in reaching its technological and commercial potential, and other future events. You should not place undue reliance on forward-looking statements because they involve known and unknown risks, uncertainties, changes in circumstances and other factors that are, in some cases, beyond Pacific Biosciences control and could cause actual results to differ materially from the information expressed or implied by forward-looking statements made in this press release. Factors that could materially affect actual results can be found in Pacific Biosciences most recent filings with the Securities and Exchange Commission, including Pacific Biosciences most recent reports on Forms 8-K, 10-K and 10-Q, and include those listed under the caption Risk Factors. Pacific Biosciences undertakes no obligation to revise or update information in this press release to reflect events or circumstances in the future, even if new information becomes available.

Contacts

Investors: Trevin Rard 650.521.8450ir@pacificbiosciences.com

Media: Colin Sanford 203.918.4347colin@bioscribe.com

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Leading UK Core Labs Expand Investment in PacBio Sequencing Systems to Power Life Science Research with HiFi Reads - GlobeNewswire

Investigators find clues in large database of Kaiser Permanente members

By Jan Greene

People can look to the Northern European side of their genetic heritage for increased risk of nonmelanoma skin cancer, according to the first large analysis of genetic risk factors for cutaneous squamous cell carcinoma in diverse populations with European ancestry. The study was published Dec. 14 in the journal Communications Biology.

Hlne Choquet, PhD, staff scientist, Division of Research

The authors examined people of varying race and ethnicity who participated in the Kaiser Permanente Research Program on Genes, Environment and Health (RPGEH). They focused on the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort, a subgroup of more than 100,000 Kaiser Permanente Northern California members who volunteered their genetic and medical information for research.

We knew that people of European ancestry with lighter skin have a higher risk of cutaneous squamous cell carcinoma, said lead author Hlne Choquet, PhD, a staff scientist with the Kaiser Permanente Division of Research (DOR). We wanted to find out the risk both within and between European ancestry populations and other populations, and whether there are genetic factors involved, and it appears that there are.

Cutaneous squamous cell carcinoma is a common cancer and its incidence is increasing not only in non-Hispanic white people but also in Latinos and Asians. While it is not usually life-threatening, if allowed to grow it can become disfiguring, spread, and even become deadly.

Latinos are complex to study because they may have ancestry deriving from multiple continents; a 2015 study of the GERA cohort by the same research group found most of those who described themselves as Latinos have European genetic ancestry along with Native American ancestry, and some have evidence of African ancestry as well.

Scatter plot shows cutaneous squamous cell carcinoma prevalence by genetic ancestry in GERA cohort; axes reflect first 2 principal components of ancestry.

In this study, the researchers examined records of 11,396 people with cutaneous squamous cell carcinoma and 86,186 control subjects in the GERA cohort and found widely varying risk by race or ethnicity group: 14% for non-Hispanic white people, compared with 3.5% for Latinos, 0.8% for East Asians, and 0.4% for African Americans.

The analysis went on to consider genetically predicted skin pigmentation, genetic risk factors for cutaneous squamous cell carcinoma, and a clinical marker for chronic sun exposure (actinic keratoses). This found that skin pigmentation accounts for a large amount of the difference within and between white people and Latinos, but not all of it. Sun exposure is also a major contributing factor.

For Latinos, the percentage of Northern European ancestry at one particular location in the genome (the SLC24A5 locus) was strongly correlated with cutaneous squamous cell carcinoma risk. The researchers also found that this risk could differ among Latinos, depending on which version of a genetic variant they inherited at the SLC24A5 locus, which is known to influence skin pigmentation.

These findings suggest skin pigmentation alone may not be the primary determinant of cutaneous squamous cell carcinoma in Latinos, but rather the specific genetic factors underlying that pigmentation, said co-author Neil Risch, PhD, an adjunct investigator with DOR and the founding director of the Institute for Human Genetics at the University of California, San Francisco.

This is a striking example of a health disparity due largely to genetics, Risch said. The GERA cohort had limited numbers of East Asian and African American patients with cutaneous squamous cell carcinoma so we could not do a deep genetic analysis in this study but future research should explore these populations to better understand the role of their genetics and environmental exposures. For example, East Asians, who also have fair skin, appear to be strongly protected from the same skin cancer.

Lifestyle factors such as sun exposure, use of sunscreen, and smoking also affect skin cancer risk, as does immunosuppression and use of certain medications.

For clinicians, the research is a reminder that our patients of Latino ethnicity, particularly those with a lighter skin phenotype, are at risk for skin cancer, and would benefit from increased awareness, education, and skin cancer screening initiatives, said senior author Maryam Asgari, MD, MPH, an adjunct investigator with DOR, associate dermatologist at Massachusetts General Hospital, and professor of dermatology and population medicine at Harvard Medical School.

The study was funded by various grants from the National Institutes of Health.

Co-authors also included co-lead author Eric Jorgensen, PhD, a former DOR research scientist; Jie Yin and Catherine Schaefer, PhD, of DOR; and Thomas J. Hoffmann, PhD, Yambazi Banda, PhD, and Mark N. Kvale, PhD, of the UCSF Institute for Human Genetics.

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Unique genetic factors and ancestry, along with lifestyle, influence skin cancer risk - Kaiser Permanente Division of Research

press release: The registration link will be the same through the end of May 2021. Presentations and Q&A will be posted later on the WN@TL YouTube site.

On January 20 Claudia Solis-Lemus of Plant Pathology and the Wisconsin Institute for Discovery presents on Through the Looking-Glass of Data Science."

Description: Big data is creating a big splash. In 2020 we expect 2.7 million job openings in Data Science in the US alone -- 10 times more than publichealth, another fast-growing field. But what exactly is Data Science? In this talk, I will describe my research as a statistician in a PlantPathology department, and how Data Science is revolutionizing the way we study plants and microbes. Statistics exploits the power ofbig data, redefining the way in which we do science by allowing us to spark discovery out of the massive amounts of data that are beingcollected in every scientific field. I will describe specific examples related to soil and plant microbiome, and illustrate how the generalapplicability of statistical tools can help translate methodologies that we use in plants to human research, in particular, to gut and lungmicrobiome.

Bio: I grew up in Mexico City, where I did my undergraduate work at the Instituto Tecnologico Autonomo de Mexico in Actuarial Sciencesand Applied Mathematics. I did my Ph.D. in Statistics at the University of WisconsinMadison, and then a postdoc here as well in theDepartment of Botany. After that, I did a postdoc at Emory University in the Department of Human Genetics. Now, I am an assistantprofessor jointly affiliated with the Wisconsin Institute for Discovery and the Department of Plant Pathology.

Links:

http://crsl4.github.io/

https://ecals.cals.wisc.edu/2019/10/09/new-faculty-profile-claudia-solis-lemus-develops-statistical-models-to-answer-biological-questions/

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ONLINE: Wednesday Nite at the Lab - Isthmus

News Release

Thursday, December 10, 2020

The National Institutes of Healths All of Us Research Program has begun to return genetic results to participants who have donated biosamples for research. This reflects the programs priority to give back information to its research volunteers. Initially, participants can choose to receive information about their genetic ancestry and traits, with health-related results available at a later date.

The All of Us Research Program is working to build a diverse community of 1 million or more participant partners across the U.S. to help researchers learn more about how genetics, environment and lifestyle factors affect health outcomes. Participants share information in a variety of ways, including surveys, electronic health records, biosamples (blood, urine and/or saliva) and more. Data is stripped of personal identifiers and made available for research through the All of Us Research Hub.

As part of its core values, the program is committed to ensuring that participants have access to their own information, and many participants have expressed a strong desire to understand what their DNA can tell them.

Were changing the paradigm for research, said Josh Denny, M.D., All of Uss chief executive officer. Participants are our most important partners in this effort, and we know many of them are eager to get their genetic results and learn about the science theyre making possible. Were working to provide that valuable information in a responsible way.

The program's in-depth genetic analyses include both whole genome sequencing and genotyping. Whole genome sequencing focuses on the more than 3 billion base pairs in the human genome, while genotyping looks at millions of genetic variants focused on peoples most common genetic differences.

To return genetic information, the program has developed a robust informed consent process, giving participants information and choice about whether or not to receive results and which results they want to get back. The program also provides access to genetic counselors to help answer questions from participants and their health care providers.

All of Us teamed up with a network of awardees across the country to support this work, including the health technology company Color, to return the personalized results on genetic ancestry and traits, and a set of leading genome centers to generate the genetic data: Baylor College of Medicine, the Broad Institute and the Northwest Genomics Center at the University of Washington, alongside their partners.

With the All of Us Research Program, were beginning to return results for a genomics program that is of unprecedented scale, said Alicia Zhou, Ph.D., chief science officer at Color. For a long time, the research community has recruited participants into large-population genomics studies without returning any results back to them. With All of Us, weve provided the tools to do just thatin a convenient and accessible way. We now have a real opportunity to return value to participants.

All of Us is taking a phased approach to the return of genetic results and will offer additional results over time. In about a year, the program plans to begin offering participants the option to receive information about how their DNA may affect their bodys response to certain types of medicines (pharmacogenetics), and about genetic variants associated with the increased risk of certain diseases, based on guidelines of the American College of Medical Genetics and Genomics. Participants will receive information back as their DNA samples are processed, so not everyone will receive information immediately.

Since All of Us opened enrollment nationwide in 2018, more than 270,000 people have contributed biosamples and more than 80 percent come from communities that are historically underrepresented in biomedical research. These include racial and ethnic minorities, sexual and gender minorities and other groups.

We need programs like All of Us to build diverse datasets so that research findings ultimately benefit everyone, said Brad Ozenberger, Ph.D., All of Uss genomics director. Too many groups have been left out of research in the past, so much of what we know about genomics is based mainly on people of European ancestry. And often, genomic data are explored without critical context like environment, economics and other social determinants of health. Were trying to help change that, enabling the entire research community to help fill in these knowledge gaps.

All of Us plans to begin making genetic data available to researchers in about a year, with strict privacy and security safeguards in place to protect participants information. The program seeks to engage researchers from diverse backgrounds to undertake a wide range of studies and learn more about how to tailor care to peoples different needs.

To learn more about All of Us and to join, visit JoinAllofUs.org.

About the All of Us Research Program: The mission of the All of Us Research Program is to accelerate health research and medical breakthroughs, enabling individualized prevention, treatment, and care for all of us. The program will partner with one million or more people across the United States to build the most diverse biomedical data resource of its kind, to help researchers gain better insights into the biological, environmental, and behavioral factors that influence health. For more information, visit http://www.JoinAllofUs.org and http://www.allofus.nih.gov.

About the National Institutes of Health (NIH):NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

NIHTurning Discovery Into Health

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NIH's All of Us Research Program returns first genetic results to participants - National Institutes of Health

Finding could lead to potential therapies

Researchers at McGill University are hopeful that the identification of the origin and a specific gene needed for tumour growth could lead to new therapeutics to treat a deadly brain cancer that arises in teens and young adults. The discovery relates to a subgroup of glioblastoma, a rare but aggressive form of cancer that typically proves fatal within three years of onset. The findings are published in the latest issue of the journalCell.

To complete their study, the research team, led by McGills Dr. Nada Jabado, Professor of Pediatrics and Human Genetics and Dr. Claudia Kleinman, Assistant Professor of Human Genetics, assembled the largest collection of samples for this subgroup of glioblastoma and discovered new cancer-causing mutations in a gene called PDGFRA, which drives cell division and growth when it is activated.

The researchers noted that close to half of the patients at diagnosis and the vast majority at tumour recurrence had mutations in this gene, which was also unusually highly expressed in this subgroup of glioblastoma. We investigated large public datasets of both children and adult patients in addition to those we had generated from patients samples in the lab and came to the same conclusion, PDGFRA was unduly activated in these tumours. This led us to suspect this kinase plays a major role in tumour formation explains Dr Carol Chen, a postdoctoral fellow, and Shriya Deshmukh an MD-PhD candidate in the Jabado lab and the studys co-first authors.

Employing a big data resource generated by their team using new technologies that measure the levels of every gene in thousands of individual cells, they were able to discover that this brain tumour originates in a specific type of neuronal stem cell. We used single cell analyses to create an atlas of the healthy developing brain, identifying hundreds of cell types and their traits, explains Selin Jessa, a PhD student in the Kleinman lab and co-first author on this study. Since these brain tumours retain a memory, or footprint, of the cell in which they originated, we could then pinpoint the most similar cell type for these tumours in the atlas, in this case, inhibitory neuronal progenitors that arise during fetal development or after birth in specific structures of the developing brain, adds Dr. Kleinman who leads a computational research lab at the Lady Davis Institute at the Jewish General Hospital.

An unexpected finding

The researchers note that the PDGFRA gene is not usually turned on in this neuronal stem cell population. By using sequencing technologies that measure how a cells DNA is spatially organized in 3D, notes Djihad Hadjadj, a postdoctoral fellow in the Jabado lab and the studys co-first author, We found that, exquisitely in this neuronal stem cell, the DNA has a unique structure in the 3D dimension that allows the PDGFRA gene to become activated where it shouldnt be, ultimately leading to cancer.

The finding is also important in properly classifying the tumour. Previously, this tumour type was classified as a glioma, because under the microscope, it resembles glial cells, one of the major cell types in the brain, says Dr. Jabado, who holds a CRC Tier 1 in Pediatric Oncology in addition to being a clinician scientist at the Montreal Childrens Hospital and leading a research lab focused on studying brain tumours at the Research Institute of the McGill University Health Centre. Our work reveals that this is a case of mistaken identity. These tumours actually arise in a neuronal cell, not a glial cell.

A hope for potential treatment

PDGFRA is targetable by drugs that inhibit its activity, and there are, in fact already approved drugs that target it for other cancers for which mutations in this gene are responsible, such as gastrointestinal stromal tumours. This offers hope for work into finding targeted therapies for this group of deadly brain tumours, note the researchers.

The combined studies of the genome, including at the single cell level and the genomic architecture in 3D of the tumour compared to the normal developing brain, were crucial in this study. They helped identify the specific timepoints during development where the cell is vulnerable to the cancer-driver event in these gliomas, which were revealed to be neuronal tumours. Importantly, the authors unravel genetic events that could lead to targeted therapy in a deadly cancer. Our findings provide hope for improved care in the near future for this tumour entity as these exquisite vulnerabilities may pinpoint to treatments that would preferentially attack the bad cells, say Drs. Jabado and Kleinman, who have joined efforts in the fight against deadly brain tumour. Stalled development is at the root of many of these cancers. The same strategy will prove important to unravel the origin, identify and exploit specific vulnerabilities, and orient future strategies for earlier detection in other brain tumour entities affecting children and young adults.

This study was made possible in large part thanks to support from the Genome Canada LSARP project Tackling Childhood Brain Cancer at the root to improve survival and quality of life, which includes funding from Genome Canada, Genome Quebec, CIHR and other sources, as well as the Fondation Charles-Bruneau and the National Institutes of Health.

Histone H3.3G34-Mutant Interneuron Progenitors Co-optPDGFRAfor Gliomagenesis, by C. Chen, S. Deshmukh, S. Jessa, D. Hadjadj, C. Kleinman, N. Jabado, et al, was published in the journalCellon December 10, 2020. DOI:https://doi.org/10.1016/j.cell.2020.11.012

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Researchers identify the origin of a deadly brain cancer - McGill Newsroom