Category Archives: Genome

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New York, NY When doctors cant find a diagnosis for a patients disease, they turn to genetic detectives. Equipped with genomic sequencing technologies available for less than 10 years, these sleuths now routinely search through a patients DNA looking for mutations responsible for mysterious diseases.

Despite many successes, the search still comes back empty more often than not. In fact, disease-causing mutations are found in only about one in three to four patients suspected of having a strongly genetic condition.

A big reason why most investigations turn up empty-handed is the dark genome. Only two percent of the human genome is well understood by scientists. This small fraction contains the 20,000 genes that encode instructions for making the cells proteins. The remaining 98 percentthe dark genomeis largely a mystery. Although its known that the dark, non-coding genome regulates genesturning them on and off, for examplethe details remain obscure.

As a consequence, sequencing data from the entire genome is currently considered almost uninterpretable, saysDavid Goldstein, PhD, the John E. Borne Professor of Medical and Surgical Research and director of the Institute for Genomic Medicine at Columbia University Medical Center, and todays genetic detectives restrict their search for disease-causing mutations to the sliver of genome that contains protein-coding genes.

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To help locate pathogenic mutations in the vast non-coding genome, Dr. Goldstein and his colleagues Ayal Gussow and Andrew Allen have developed a new technique called Orion. Orion is designed to flag regions of the non-coding genome that are likely to contain disease-causing genetic changes by identifying parts of the genome that are under selection in the human population.

We anticipate that researchers will immediately start using Orion to help them find pathogenic mutations in patients in which previous sequencing efforts were negative, says Dr. Goldstein. Details about the method were published online Aug. 10 in PLoS One.

Orion was developed by comparing the entire genomes of 1,662 people and identifying stretches of DNA that vary little from person to person. Because these regions are intolerant to change, they are most likely doing something important, says Dr. Goldstein, lead author of the paper.

That means a mutation in an intolerant region is more likely to cause disease than a mutation in a tolerant (read: less important) region. This prediction was confirmed when the researchers mapped the locations of previously identified non-coding mutations: More mutations fell within Orions intolerant regions.

Previous methods to explore the non-coding genome focused on areas of the non-coding genome that have been retained in multiple species over evolutionary time, suggesting they, too, have an important function. However, this approach is not able to identify regions of the genome that have taken on important new functions in humans.

Orion isnt yet a finished product, Dr. Goldstein says. As more genomes are sequenced, the resolution of Orions regions will improve dramatically.

At that point, we are optimistic that Orion will constitute one helpful tool in the effort to identify variants throughout the genome that influence the risk of both rare and common diseases, says Dr. Goldstein.

Thestudyis titled Orion: Detecting Regions of the Human Non-Coding Genome that are Intolerant to Variation Using Population Genetics. Authors are Ayal Gussow (Duke University, Durham, NC, and Columbia University Medical Center, New York, NY), Brett Copeland (CUMC), Ryan Dhindsa (CUMC), Quanli Wang (CUMC), Slave Petrovski (CUMC and University of Melbourne, Victoria, Australia), William Majoros (Duke), Andrew Allen (Duke), and David Goldstein (CUMC).

The study was supported by the National Institutes of Health (1U01MH105670, 1UM1HG00901,F31NS092362,RC2NS070344;U01NS077303;U01NS053998,RC2MH089915,K01MH098126,R01MH097971,U01HG007672, andUM1AI100645); Biogen Inc.; SAIC Fredrick Inc.; the Joseph and Kathleen Bryan Alzheimers Disease Research Center; the Duke Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery; the Bill and Melinda Gates Foundation; the Ellison Medical Foundation; and the Murdock Study Community Registry and Biorepository.

David Goldstein is a founder of and holds equity in Pairnomix and Praxis and receives support from Janssen, Gilead, Biogen, AstraZeneca, and UCB. The authors declare no other conflicts of interest.

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New Technique Searches 'Dark Genome' for Disease Mutations - Lab Manager Magazine

Like a fast-growing child constantly outgrowing clothes, biotech giant Illumina has trouble keeping up with its continued expansion.

So on Monday, the San Diego genome sequencing leader is scheduled to open a new addition a 7-acre, 316,000 square-foot complex called the i3 campus. Illumina considers it an extension of its headquarters, less than a mile away in the University Town Center area.

Consisting of three buildings refitted for Illuminas needs, the i3 campus emphasizes openness, with ample windows to the outside and an open-style office space inside. Amenities include a gym and a restaurant called Salt + Air.

And there are meeting rooms lots of meeting rooms. Larger rooms, for formal presentations, can be reserved. Smaller ones, where one or two people can sit, are available on the fly for the innumerable spontaneous discussions that seem to be baked into Illuminas DNA.

Employees manage their own day and calendars, so we infused the i3 workplace with open and non-bookable places for employees to work these can be visitors from the main HQ campus or employees from another site, said Jenny Durbin, the companys global facilities manager. An employee can choose to work at i3 even if their team or department is based at the main campus.

Illumina employs almost 7,000 people, nearly 3,000 of them in San Diego. Its stock is valued at more than $28 billion, making it by far the highest valued biotech in San Diego.

In January 2014, Illumina made international headlines by bringing down the cost of sequencing a human genome to below $1,000, with its HiSeq X Ten Sequencing System. And this January, the company announced machines in its NovaSeq line that can reduce the time to process a human genome to an average rate of one per hour, when many are processed in large batches.

As a result of such advances, Illumina dominates the market for DNA sequencers. It also leverages genomic technology into such fields as prenatal testing.

Since its impossible to know what scientific research will lead to new opportunities, Illumina makes sure its employees have flexibility, Durbin said. As biomedical research unveils new breakthroughs, Illumina races to translate the research into new products to serve the field, in government, academic and medical applications.

The i3 campus was developed by BioMed Realty, designed by the Seattle architectural firm of Perkins + Will, and built by McCarthy contractors. Tucked onto seven acres at the east end of Executive Drive, its cantilevered buildings perched like hawks over Interstate 805.

Theres a common theme working up and down the coast, said design principal Ryan Bussard, looking for innovation in architecture, tying together site design as well as architecture and collaboration spaces. The indoor and outdoor down here you can really take advantage of that year-round. Its pretty unique.

BioMed Realty held a design competition in 2011 that Perkins + Will won, five years before Illumina signed a lease for the property, and the architects and developers had to conceive a building before the users needs were known.

One of the first decisions was to demolish a never-occupied building and locate parking underground to gain more above-ground usable space.

The siting of the building was kind of a invert of the traditional, Bussard said.

That cost more but yielded highly valued space, including a 33,500-square-foot courtyard.

The second decision was to build three concrete-and-glass buildings and cantilever them out toward I-805 as much as 30 feet beyond the lower floors. The effect is to float above the landscaped fire lane where the company will host its first big event next month.

Its almost weightless, he said.

The local inspirations? The Salk Institute and the J. Craig Venter Institute on Torrey Pines Mesa. About 40,000 cubic yards of smooth white concrete make up the structure, rather than a more traditional steel-and-glass framework.

That eliminated the need to locate elevators, bathrooms and other core facilities in the middle of the buildings and increased the flexibility of each floors layout.

The third decision was to set aside half the building to be used for lab space on the interiors and administrative space around the exterior walls. But Illumina chose to make the entire building into office space a shift that could be reversed in the future.

We build flexible space for the infrastructure to support, Bussard said.

Inside the three buildings, the finance, marketing and other company executives will work to turn researchers inventions and findings into products and services.

Perkins + Will designers took the companys philosophy of work anywhere and created interior design layouts that decouple staff from their desktop phones, computers and potted plants.

Large and small meetings will be scheduled in a variety of ground-floor spaces in Building B, located to the right of the campus entrance. One conference room can be extended to about 120 feet in length and voice-sensitive cameras can transmit the proceedings off campus.

A smaller plaza lounge at the end of the building offers a more informal space in a midcentury modern, 60s residential look. Durbin, the global facilities manager, called the approach resimercial a mashup of residential and commercial design.

Its a blend between formal spaces and a more home-like space, she said.

To orient employees no matter where they work, the same colors are being used floor by floor the first floor is pumpkin orange, the second is blue and the third green. Abstract carpet patterns complement the color scheme.

Its important to have innovation and consistency, said Norm Fjeldheim, senior vice president, chief information officer and head of global facilities.

Some employees will have assigned desks that can be adjusted for standing or sitting, while others can move day to day, depending the task at hand. At night they can store their personal items in lockers. For private phone conversations, there are 60 phone booths in the complex but bring your own cell phone that links into the buildings WiFi network.

Those desks and phone booths will be used by people not only from San Diego, but from around the world.

Besides San Diego, Illumina has offices in Hayward, Santa Clara, San Francisco, Redwood City, Madison, Wis.; and internationally in Victoria, Australia; Shangai and Beijing; Tokyo; So Paulo; Eindhoven, the Netherlands; Chesterford and Fulbourn, United Kingdom; Singapore; and Victoria, Canada.

As a company with a worldwide presence, Illumina uses technology to bridge the gap between its widespread locations, said Durbin said.

I feel as an employee working across the globe that my team members and colleagues at the other sites feel just as close to me as my team mates here, because we make the efforts to use the technology (Jabber, message, box, video and teleconferencing) to bridge the distance, Durbin said.

In San Diego, Illuminas presence goes far beyond its direct employment. Local biomedical institutions such as Scripps Health, the J. Craig Venter Institute and Rady Childrens Hospital San Diego are Illumina customers. Illumina is also a longtime charitable supporter of Rady Childrens.

When babies show up at the hospital with unidentifiable serious illnesses, their genomes may be sequenced with Illumina products to find clues to their condition. This can save lives and prevent unneeded procedures.

Shimul Chowdhury, Rady Childrens clinical laboratory director, used to work for Illumina. As a board-certified molecular geneticist, he analyzes the genetic data from clinical reports and delivers them to physicians.

My role as a laboratory director is really to be the bridge between the laboratory who presents the reports to our physicians in a manner that they understand and that is useful for them to be able to take care of their patients, Chowdhury said.

At Illumina, he worked in the clinical laboratory, seeking to learn what information could be gleaned from a genome to make genome sequencing become routine in clinical practice. That required him to analyze patient samples and collaborate with doctors. He collaborated with Dr. Stephen Kingsmore, who heads the Rady Institute for Genomic Medicine.

As Chowdhury learned more about Rady Childrens, he decided to join the hospital to help put genomic technology into clinical practice. And his work still very much involves technology from Illumina.

Theyre providing the instruments and the reagents (supplies) to help us sequence kids, Chowdhury said. But it goes broader than that in terms of collaboration. Were taking these sequencing technologies and testing them in patients in intensive care units. So I think our feedback is valuable to them.

On a larger scale, he said Illuminas presence in San Diego draws visibility to use of the technology.

It really increases the genomics literacy of this region, which really helps us when were speaking to families, speaking to doctors, he said.

Radys uses Illuminas most advanced genomics instrument, the NovaSeq, Chowdhury said. With speed and accuracy, the instrument is important for searching for genetic causes of disease in children who may be critically ill and not have much time left.

We really view this machine as a next step in our evolution for being able to provide rapid genomes for more and more kids in San Diego and throughout the United States, he said.

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bradley.fikes@sduniontribune.com

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Genome leader Illumina expands again in San Diego - The San Diego Union-Tribune

Using the genome-editing technology CRISPR, scientists deactivated a family of retroviruses within the pig genome overcoming a large hurdle in the path to the transplant of pig organs into humans.

Transplantation from one species to another -- xenotransplantation -- holds "great promise," the American and Chinese research team believes.

Retroviruses carry their genetic blueprint in the form of ribonucleic acid (or RNA) and transcribe this into deoxyribonucleic acid, commonly known as DNA. This is a reverse of the usual transcription process, which flows from DNA to RNA. This reversal makes it possible for retrovirus genes not only to infect cells but to become permanently incorporated into a cell's genome.

In particular, the pig genome is known to carry porcine endogenous retroviruses (or PERVs), which are capable of transmitting diseases, including cancers, into humans. The presence of these PERVs means pig organs cannot now be safely transplanted into humans.

But George Church of MIT's Broad Institute and Harvard, Dong Niu of Zhejiang University and their colleagues demonstrated a new method for deactivating the retroviruses in a pig cell line as a way to eliminate the transfer of PERVs to human cells.

First, the researchers proved that PERVs can be transmitted from pig to human cells and transmitted among human cells, even in conditions in which the fresh human cells have no prior exposure to pig cells.

Next, the team created a map of the PERVs in the genome of pig fibroblast (connective tissue) cells. Having identified a total of 25 PERVs, the science team used CRISPR to edit out -- or deactivate -- all those gene sites.

The scientists grew clone cells of these edited cells but were unable to cultivate one with greater than 90% of the PERVs deleted. But they added "ingredients" during the gene modification process -- including both growth factors and growth inhibitors -- and finally succeeded.

The new cells had 100% of the PERVs deactivated.

From here, the researchers produced PERV-inactivated embryos and implanted them into sows. The resulting piglets exhibited no signs of PERVs.

Dr. Ian McConnell, emeritus professor of veterinary science at the University of Cambridge, sees the research as a "promising first step." McConnell, who was not involved in the study, added that "it remains to be seen whether these results can be translated into a fully safe strategy in organ transplantation."

Formidable obstacles remain "in overcoming immunological rejection and physiological incompatibility of pig organs in humans," he said.

Scientists have been introducing human cells into animals to create models of diseases for decades, yet the 2009 policy suspended funding for chimera-based research due to ethical concerns.

With the advance of both stem cell and gene editing technologies, the ability to create more sophisticated animal-human chimeras raised concerns. Worries include human cells populating the brain of an animal thus humanizing that animal. Alternatively, human cells populating the germline of an animal could enable human genes to pass onto offspring.

The National Institutes of Health hopes a revised policy will enable research to continue -- safely.

The new research supports the value of using CRISPR to deactivate PERVs and so brings pig organs one step closer to safe transplantation, concluded the scientists.

Though more research is needed, they believe the "PERV-inactivated pig" can serve as a foundation strain that might be further engineered to "provide safe and effective organ and tissue resources" for transplantation into humans.

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Scientists edit pig genome with goal of human organ transplants - CNN

What is it?

In a first, researchers from the Oregon Health and Science University along with colleagues in California, China and South Korea repaired a mutation in human embryos by using a gene-editing tool called CRISPR-Cas9.

The mutation seen in the MYBPC3 gene causes a common heart condition called hypertrophic cardiomyopathy, which is marked by thickening of the heart muscle.

The mutation is seen in about one in 500 people and can lead to sudden death later in life. It is an inherited cardiac disease and the presence of even one copy of the gene can cause symptoms, which usually manifest as heart failure. Correcting the mutation in the embryo ensures that the child is born healthy and the defective gene is not passed on to future generations. There is currently no cure for the condition.

How did it come about?

CRISPR-Cas9 is a system used by bacterial cells to recognise and destroy viral DNA as a form of adaptive immunity. Using components of the CRISPR system, researchers can remove, add or alter specific DNA sequences in the genome of higher organisms.

The gene editing tool has two components a single-guide RNA (sgRNA) that contains a sequence that can bind to DNA, and the Cas9 enzyme which acts as a molecular scissor that can cleave DNA. The genetic sequence of the sgRNA matches the target sequence of the DNA that has to be edited. In order to selectively edit a desired sequence in DNA, the sgRNA is designed to find and bind to the target.

Upon finding its target, the Cas9 enzyme swings into an active form that cuts both strands of the target DNA. One of the two main DNA-repair pathways in the cell then gets activated to repair the double-stranded breaks. While one of the repair mechanisms result in changes to the DNA sequence, the other is more suitable for introducing specific sequences to enable tailored repair. In theory, the guide RNA will only bind to the target sequence and no other regions of the genome.

But the CRISPR-Cas9 system can also recognise and cleave different regions of the genome than the one that was intended to be edited. These off-target changes are very likely to take place when the gene-editing tool binds to DNA sequences that are very similar to the target one. Though many studies have found few unwanted changes suggesting that the tool is probably safe, researchers are working on safer alternatives.

Why does it matter?

Along with sperm from a man with hypertrophic cardiomyopathy, the gene-editing tool was also introduced into eggs from 12 healthy women before fertilisation. In normal conditions, a piece of DNA with the correct sequence serves as a template for the repair to work, although the efficiency can be significantly low. Instead of the repair template that was provided by the researchers, the cells used the healthy copy of the DNA from the egg as a template. This came as a big surprise.

Normally, if sperm from a father with one mutant copy of the gene is fertilized in vitro with normal eggs, 50% of the embryos would inherit the condition. When the gene-editing tool was used, 42 out of the 58 embryos did not carry the mutation. The remaining 16 embryos had unwanted additions or deletions of DNA.

Thus the probability of inheriting the healthy gene increased from 50 to 72.4%. There was no off-target snipping of the DNA. According to Nature, the edited embryos developed similarly to the control embryos, with 50% reaching an early stage of development (blastocyst). This indicates that editing does not block development.

What next?

Clinical trials are under way in China and in the U.S. to use this tool for treating cancer. In May this year, it was shown in mice that it is possible to shut down HIV-1 replication and even eliminate the virus from infected cells. In agriculture, a new breed of crops that are gene-edited will become commercially available in a few years. In February this year, the National Academy of Sciences (NAS) and the National Academy of Medicine said scientific advances make gene editing in human reproductive cells a realistic possibility that deserves serious consideration.

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What is genome editing? - The Hindu

In a collaborative effort across a number of institutions, including Harvard, the Dana-Farber Cancer Institute, and the Broad Institute of MIT, researchers have narrowed down 760 genes directly responsible for the survival of cancer cells.

Although most of the vulnerable genes vary from one cancer type to another, around 10 percent are consistent between types, making them possible targets for cancer-fighting therapies.

The study, published in the journal Cell, utilized small interfering RNA, or siRNA, to turn off single lines of DNA and see which cells were affected. Overall, 17,000 genes were tested in over 20 different kinds of cancer.

Even though so many genes were studied, 90 percent of the cancers tested only vitally relied on 76 sets of genes, indicating that many other cancers may also have a small core of key genes that can be exploited as treatment targets.

Additionally, a scientist used biomarkers to divide cells into groups that describe their role in biology with over 400 of the 769 mapped genes.The groups account for roles such as gene mutation, reduced or increased gene expression, and gene function.

Through the study, it was discovered that 20 percent of the vital genes were already targeted for existing drug therapies, providing more proof of their efficacy.

While the full cancer genome hasnt been identified for all types, the work is well under way, meaning doctors and scientists have more information with which to battle cancer and help patients with better treatments.

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Early Version of Cancer Genome Reveals Vital Vulnerabilities - TrendinTech

When it comes to CRISPR, our society has some important decisions to make.

Just last week, scientists reported a new first in the journal Nature: They edited heritable cells in human embryos to treat an inherited form of heart disease. The day after the research was published, a group of genetics experts published a statement calling for further debate before applications of the technology are taken any further in humans.

According to a new survey of 1,600 adults published in the journal Science today, much of the American public shares this desire for engagement in decision-making. Led by Dietram Scheufele, a professor of science communication at the University of Wisconsin - Madison, the study found that while support for gene editing applications varies, a majority of respondents think the public should be consulted before genome editing is used in humans.

Gene editing presents the potential for remarkable benefits.

The potential to cure genetic disease and to ensure the safety of the world's food supply in the face of climate change are perhaps the most exciting opportunities, said Jennifer Doudna, a chemist at UC Berkeley who was an early pioneer of the powerful gene-editing technique CRISPR-Cas9 and was not involved in the new study.

But it also raises some serious ethical questions, especially when we turn our attention to tweaking the human genome, Scheufele said. Many people find some applications like disease treatment valuable, and others like making your children more intelligent morally shaky.

For example, scientists may eventually develop a cure for what some people dont consider an illness like a disability, Scheufele said. Would those who chose not to undergo genetic therapy or who couldnt afford it then be discriminated against even more as a result?

These and other ethical concerns go beyond the bounds of science, Scheufele says, and his poll results show that the public wants to be involved in the debate.

Oregon Health & Science University

Embryos develop into blastocysts after co-injection, which could someday be used in fertility clinics to help people trying to have children free of genetic disease.

Embryos develop into blastocysts after co-injection, which could someday be used in fertility clinics to help people trying to have children free of genetic disease. (Oregon Health & Science University)

Because of the fast-moving progress of gene editing research and the vast potential for both beneficial applications and negative consequences, many experts have called for public engagement on the issue including in a consensus report released this year by the National Academy of Sciences (NAS) and the National Academy of Medicine (NAM).

The new study strove to answer some questions emerging from the National Academies report. First, how do people feel about different applications of gene editing? And secondly, do Americans agree that the public should be consulted on gene editing applications? Similar questions had been asked in previous polls, but the authors wanted to get some more specific data.

Human genome editing can be used for two broad purposes: therapy or enhancement. Therapeutic applications include the treatment of genetic disorders like muscular dystrophy or sickle cell disease, while enhancement might be used to change your daughters eye color or make her grow taller.

Each of these changes can be heritable or not, depending on which type of cell is tweaked. Somatic cells are nonreproductive, so any changes to these cells will not be passed on to future generations. Germline cells, on the other hand, are heritable therefore, any modifications will be inherited by the treated persons children and grandchildren.

Reprinted with permission from D.A. Scheufele et al., Science 357:6351 2017

A graphic from the paper showing the acceptance of gene editing by application.

A graphic from the paper showing the acceptance of gene editing by application. (Reprinted with permission from D.A. Scheufele et al., Science 357:6351 2017)

The new poll shows that two-thirds of Americans support therapeutic applications, whether to somatic (64% support) or germline (65% support) cells. When it comes to enhancement, however, there is much less approval. Only 39% of respondents find somatic enhancement acceptable, with 35% saying it is unacceptable. Levels of support dropped even lower for heritable germline enhancement, to 26% in acceptance and 51% in opposition.

When these results were broken down by how religious respondents were, some variation emerged. Religious people are less supportive of genome editing overall. Only half of them expressed some support of treatment applications, compared with 75% of nonreligious respondents. When it comes to enhancement, 28% of religious respondents and 45% of nonreligious people reported some level of support.

The authors also ranked respondents in terms of low, medium and high knowledge by their score on a nine-question factual quiz. Those in the high-knowledge category were far more supportive of treatment applications, with 76% in support compared with only 32% of low-knowledge respondents.

When asked about enhancement applications, the high-knowledge group was very polarized, with 41% in support and a nearly equal amount in opposition. In contrast, half of low-knowledge people reported that they neither support nor oppose gene editing.

Robert Blendon, who studies health policy at the Harvard School of Public Health, said that the polarization could be there for a reason. Those who know more about the technology have probably learned about it because they have a vested interest maybe a genetic disease runs in their family or they are concerned with ethical consequences.

Reprinted with permission from D.A. Scheufele et al., Science 357:6351 2017

A graphic from the paper showing the opinions of respondents based on religiosity and knowledge.

A graphic from the paper showing the opinions of respondents based on religiosity and knowledge. (Reprinted with permission from D.A. Scheufele et al., Science 357:6351 2017)

The more religious people were, the less likely they were to trust the scientific community to responsibly develop new technologies. This trend was opposite when it came to knowledge: The more knowledgeable people were about the technology, the more likely they were to trust the scientists.

While the two groups may have very different reasons, both highly religious and highly knowledgeable people agreed that the public should be involved in decision-making before gene editing is used in humans.

Blendon said that while its clear the public wants a say in how gene editing is used, its unclear exactly what public engagement looks like. The first way most people might think of being consulted is through their elected officials, but other surveys suggest that the public actually doesnt think the government should be making decisions about genome technology.

Scheufele said that there is currently no infrastructure in place for crucial two-way communication between scientists and the public on the genome editing issue but its important to develop it.

Diverse groups and perspectives have an important role to play in shaping the early stages of human genome editing research, Scheufele said. Scientists may not think to investigate all the questions that the public may deem vital.

If we ask the wrong questions, he said, then we may have perfect technical answers to all the wrong questions.

mira.abed@latimes.com

@mirakatherine

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Americans want a say in human genome editing, survey shows - Los Angeles Times

Americans have conflicting views on how technologies that allow human genome editing, such as one that uses the Cas9 enzyme to snip DNA, should be employed.

Meletios/shutterstock

By Jon CohenAug. 10, 2017 , 2:40 PM

CRISPR, the powerful genome-editing tool, does a molecular tango to cut and modify DNA that is highly nuanced. The same subtlety applies to the publics views on how best to use genome editing in humans, a new survey of adults in the United States shows.

Earlier surveys of Americans (here and here) have found a reluctance to support human genome editing, with many respondents expressing ethical and other concerns about such intentional tinkering. But the new survey, conducted by social scientists from the University of Wisconsin (UW) in Madisonand Temple University in Philadelphia, Pennsylvania, found that two-thirds of the 1600 respondents thought genome editing was generally acceptable. This held true whether the genome modification was in germline cells, which can be passed on to offspring, or in somatic cells that cannot. But that acceptance was qualified, and colored by religious beliefs and scientific knowledge. There was one thing that almost everyone agreed on, however: They want to be part of the policy discussion about what should and should not be allowed.

The survey, described today in a Policy Forum published by Science, randomly presented people with different vignettes that described genome editing being used in germline or somatic cells to either treat disease or enhance a human with, say, a gene linked to higher IQ or eye color. Although respondents were generally open to the use of editing technologies, acceptance depended strongly on the specific purpose and its impact on future generations. For instance, there was scant support for using genome editing to enhance a germline; just 26% of people found that acceptable and 51% said it was unacceptable. But acceptance jumped to 39% if the enhancement was in somatic cells, and only 35% objected.

Such results suggest that theres not a general, broad opposition to this technology, says co-author Dietram Scheufele, who specializes in science communication at UW Madison. But the survey does show very clearly that, if you look at germline enhancement in particular, thats where you see the majority of the of public expressing concern.

Such concerns are in line with previous surveys that have shown people dont like the idea of creating designer babies or populations of superhumans who pass down advantages to their offspring. But respondents to this survey were more tolerant of individuals using gene editing to improve their own bodies. For example, 59% supported using genome editing to treat a medical condition or enhance health.

But a persons religious beliefs affected their views. In people who reported low religious guidance, support for using genome editing to enhance health jumped to 79%; in the religious, it dropped to 50%.

The researchers also asked nine factual questions about genome editing and found sharp differences in support for both treatment and enhancement based on knowledge. In respondents who could not answer any of the nine questions correctly, support for treatment fell to 32% and enhancement to only 19%. Among those who answered at least six questions correctly, support for treatment rose to 76%, and for enhancement to 41%.

The Pew Research Center in Washington, D.C., conducted one of the earlier surveys that revealed hesitancy, finding that 68% of the respondents were very or somewhat worried about gene editing. But Cary Funk, a social psychologist at Pew who helped lead that 2016 survey, says those findings are broadly in keeping with the new survey, again underscoring the nuances. As Funk notes, both surveys show that public views about gene editing vary depending on whether the techniques would involve germline editing or testing on human embryos and that there are wide differences based on religious beliefs.

Scheufele says one of the surveys most important findings is that everyone wanted what he and his colleagues refer to as engagement in discussions about genome-editing regulation and policy. He says some of his colleagues have dismissed the need for such engagement because they contend its still too hypothetical: Scientists and clinicians cant yet safely and efficiently do the types of genome editing that are being envisioned. That argument is faulty, Scheufele says. We need to have the discussion exactly because the science isnt there yet. Once we can do it, the question becomes should we? and that should be answered long before we get there.

The U.S. National Academy of Sciences and National Academy of Medicine in February published an influential report, Human Genome Editing: Science, Ethics, and Governance, that has an entire chapter on public engagement. The natural question that follows [the new survey] is what kind of public engagement? says UW Madisons Alta Charo, a bioethicst and lawyer who co-chaired the academies committee that wrote the report. (Scheufele was also on the committee.) Charo, who was not involved in the new survey, notes that engagement can mean everything from teaching classes to holding meetings that join scientists with religious leaders, or give the public a forum to express views and concerns to policymakers.

Scheufele acknowledges that public engagement remains a fuzzy concept. He notes that the Royal Society in London has held meetings aimed at improving engagement, but U.S. groups dont really have the infrastructure in place. We need a much bigger structure for public engagement or otherwise it becomes handwaving.

He and his team now are planning to conduct a survey about what kinds of engagement mechanisms could help avoid the sort of polarization seen in policy debates over genetically modified crops or climate change. How can we have those broader discussions without falling into the trap of our values dividing us more and more, he says, and instead have a productive discussion that allows us to move forward?

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Americans are becoming more open to human genome editing ... - Science Magazine

After a thorough antivirus scan, de-bugged pigs are a step closer to growing organs for us.

Researchers used the latest gene editing technology to deactivate 25 remnants of ancient viruses, called porcine endogenous retroviruses (PERVs), that had embedded in the DNA of a pig cell line. Pig genomes are rife with lurking PERVs, which threaten to emerge and infect humans. But with a genome wiped of active viruses, the researchers produced 37 piglets that are PERV-free. Thecreation of those clean little porkers, reported Thursday in Science, is progress toward using pigs as human organ donors, the researchers say.

Our study highlighted the value of PERV inactivation to prevent cross-species viral transmission and demonstrated the successful production of PERV-inactivated animals to address the safety concern in clinical xenotransplantation, the authors concluded.

Researchers have always worried about PERVs in pig-to-human transfers. The retroviruses, which are passed on through hog generations, have never proven to transmit to humansno human PERV disease cases have ever been reported, even in patients who have received pig tissue transplants. Still, the concern lingers. And in labs, PERVs can jump from pig cells to human cells.

Researchers saw this first hand in the new study, led by Harvard geneticist George Church and Luhan Yang, a bioengineer and president of eGenesis, a biotech start-up she and Church co-founded. Before sweeping away PERVs from a pig cell line, they showed that PERVs from a line of pig cells infected a line of human cells when researchers grew them together. And that infected line of human cells infected another line of human cells when researchers grew them together.

Theres still a lot of work ahead to turn the swine into human organ factories. And its unclear if researchers will end up needing PERV-free piglets for the feat. But for now, Church, Yang, and their team think their new pigs may serve as a foundation pig strain, which can be further engineered to provide safe and effective organ and tissue resources for xenotransplantation.

Science, 2017. DOI: 10.1126/science.aan4187 (About DOIs).

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Scientists de-bug pig genome in preparation for farming organ donors - Ars Technica

August 10, 2017 Credit: CC0 Public Domain

When doctors can't find a diagnosis for patient's disease, they turn to genetic detectives. Equipped with genomic sequencing technologies available for less than 10 years, these sleuths now routinely search through a patient's DNA looking for mutations responsible for mysterious diseases.

Despite many successes, the search still comes back empty more often than not. In fact, disease-causing mutations are found in only about 1 in 3 to 4 patients suspected of having a strongly genetic condition.

A big reason why most investigations turn up empty-handed is the "dark genome." Only 2 percent of the human genome is well understood by scientists. This small fraction contains the 20,000 genes that encode instructions for making the cell's proteins. The remaining 98 percentthe "dark genome"is largely a mystery. Although it's known that the dark, non-coding genome regulates genesturning them on and off, for examplethe details remain obscure.

As a consequence, sequencing data from the entire genome "is currently considered almost uninterpretable," says David Goldstein, PhD, the John E. Borne Professor of Medical and Surgical Research and Director of the Institute for Genomic Medicine at Columbia University Medical Center, and today's genetic detectives restrict their search for disease-causing mutations to the sliver of genome that contains protein-coding genes.

To help locate pathogenic mutations in the vast non-coding genome, Goldstein and his colleagues Ayal Gussow and Andrew Allen have developed a new technique called Orion. Orion is designed to flag regions of the non-coding genome that are likely to contain disease-causing genetic changes by identifying parts of the genome that are under selection in the human population.

"We anticipate that researchers will immediately start using Orion to help them find pathogenic mutations in patients in which previous sequencing efforts were negative," says Dr. Goldstein. Details about the method were published online today in PLOS ONE.

Orion was developed by comparing the entire genomes of 1,662 people with one another and identifying stretches of DNA that vary little from person to person. Because these regions are "intolerant" to change, they are most likely doing something important, says Dr. Goldstein, lead author of the paper.

That means a mutation in an intolerant region is more likely to cause disease than a mutation in a tolerant (read: less important) region. This prediction was confirmed when the researchers mapped the locations of previously identified non-coding mutations: more mutations fell within Orion's intolerant regions.

Previous methods to explore the non-coding genome focused on areas of the non-coding genome that have been retained in multiple species over evolutionary time, suggesting they, too, have an important function. However, this approach is not able to identify regions of the genome that have taken on important new functions in humans.

Orion isn't yet a finished product, Goldstein says. As more genomes are sequenced, the resolution of Orion's regions will improve dramatically.

"At that point, we are optimistic that Orion will constitute one helpful tool in the effort to identify variants throughout the genome that influence the risk of both rare and common diseases, says Dr. Goldstein.

Explore further: Exome sequencing unravels rare disease mysteries

More information: Orion: Detecting Regions of the Human Non-Coding Genome, PLOS ONE (2017).

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New technique searches 'dark genome' for disease mutations - Medical Xpress

UW Life Sciences Communication professors Dietram Scheufele and Dominique Brossard conducted one of the first national surveys to gauge public opinion surrounding genome editing.

Their study dove into the nuances of DNA editing asking participants their opinions on both editing DNA for just one individual, or making changes that would be passed down through generations. There are now genetic tests for sickle-cell anemia, Tay-Sachs disease, and Down syndrome, among others. Could these genes simply be edited out of the population? Harvard scientists have also announced today that gene-edited piglets could potentially be used for growing organs for human transplants.

Scheufele says, surprisingly, people arent totally opposed to making changes that would get passed down.

People distinguished very clearly between therapeutic uses and enhancement uses, Scheufele says. So if its about curing diseases, people are much more open to the idea of making edits that will be passed on through generations.

Nearly two-thirds of respondents said they support editing genes that would be passed down through generations if it meant preventing disease. Only a quarter of people supported editing those kinds of cells for cosmetic purposes, though to enhance a persons physical traits or appearance.

The study also gauged how religious respondents are, along with how much they already know about the topic. People with strong religious beliefs were both more hesitant of the technology and more doubtful that the scientific community would be able to properly regulate this technology.

People who knew more about the technology, though, were more optimistic. What didnt differ much? Their desire to be part of the conversation.

We may differ in our attitudes toward that new technology, but a lot of us agree that we really do want to be part of the conversations about some of the ethical, moral and political questions that this new technology raises.

Scheufele says the technology opens the door to practically endless moral questions Who will have access to the technology? Will it put pressure on parents to modify their kids? What long-term effects will this have on the human population?

Scheufele says often people regard those questions as premature, since the technology hasnt come that far. But he disagrees, and so do many of his respondents.

My argument would be given how complex and how challenging some of those moral questions are, we need to have the conversation long before the technology arrives, and not wait until the technologys here and not have the time to weigh them through carefully, Scheufele says.

And he says the conversation will be important as the technology continues to develop. Public conversations around a topic have shifted the direction of technology in the past especially in the case of stem cells.

Maybe theres ways in which we roll this out thats different than we originally planned, Scheufele says.

The study was published this week in the journal Science.

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UW Study Finds People Want To Talk About Genome Editing - Wortfm