Category Archives: Human Genetics

Summary: Hypermutation in children may be linked to increased mutations in the sperm of the biological father, especially fathers who received certain forms of chemotherapy to treat cancer early in life.

Source: Wellcome Sanger Institute

Some rare cases of higher genetic mutation rates in children, known as hypermutation, could be linked to the father receiving certain chemotherapy treatments, new research has found.

Scientists from the Wellcome Sanger Institute and their collaborators analyzed over 20,000 familiesgenetic informationand identified 12childrenwith between two to seven times more mutations than the general population.

The team linked the majority of these to increased mutations in thespermof the biological father.

The research, published today inNature, shows that just under half of these fathers had been treated with certain types ofchemotherapyearlier in life, which could be linked to the increased number of mutations in theirsperm cells.

While these cases of hypermutation in children are rare, and in the vast majority of children will not lead to genetic disorders, hypermutation will increase the risk of a child having arare genetic disorder. It is important to investigate this further due to the implications it has for patients who receive chemotherapy and want to have children in the future.

If further research confirms an impact of chemotherapy, patients could be offered the opportunity to freeze their sperm before treatment.

Genomes are copied with a very low error rate when they are passed from one generation to the next. Nevertheless, as thehuman genomecontains three billion letters, random mutations in the sperm and the egg are inevitable and pass from the parent to the child. This means that typically every child has around 60 to 70 new mutations that their biological parents dont have.

These mutations are responsible for genetic variation along with many genetic diseases. Around 75 percent of these random mutationscome from the father.

Most genetic disorders only occur when both copies of an important gene are damaged, resulting in what is known as a recessive disease. If only one copy is damaged, for example, by a new mutation, the remaining functioning copy of the gene will be able to prevent disease.

However, a minority of genetic disorders, known as dominant disorders, occur when only one copy of a gene is damaged. It is these dominant disorders that can be caused by a single, random mutation.

One of the main factors influencing mutation rate is the age of the parents, with mutations increasing by 1.3 mutations per year in the fathers and0.4 mutations per year in mothers. If there is a higher number of germline mutations, there is a higher risk of a child being born with a dominant disorder.

However, hypermutation in children does not always mean they will have a dominant disorder.

In new research, from the Wellcome Sanger Institute and collaborators, scientists used genetic data and family health histories from existing databases to identify children that had unusually high mutation rates, between two and seven times higher than average, to investigate where these might have originated from.

The team analyzed data from over 20,000 UK families with children with suspected genetic conditions participating in the Deciphering Developmental Disorders and 100,000 Genomes projects.

They found that children with hypermutation were rare among these families. As the number of children with hypermutations was only 12 out of around 20,000, these rates of increased mutations could not have been caused by common exposures, such as smoking, pollution, or commongenetic variation.

For eight of these children the excess mutations could be linked to their fathers sperm. It was possible to investigate in detail seven of the families, where the excess mutations came from the biological father. Two of the fathers had rare recessive genetic variants that impaired DNA repair mechanisms.

The other five men had all previously been treated with chemotherapy before conceiving a child. Three of these children had a pattern of mutations characteristic of chemotherapy using platinum-based drugs and the fathers of the other two children had both received chemotherapy with mustard-derived alkylating agents.

However, by linking the genetic data to anonymized health data, it could be shown that most fathers and all mothers who had received chemotherapy prior to conceiving a child did not have children with a notable excess of mutations.

This study exemplifies the value of linking nationwide genetic data and routine clinical records in secure, anonymized and trustworthy ways to provide unique insights into unanticipated, but important, questions.

Through the efforts of Health Data Research UK and its partners, these kinds of responsible analyses of potential clinical relevance will be easier to perform in the future.

While chemotherapy is one of the most effective treatments for cancer, it is widely recognized that it can have disruptive and debilitating side effects. Clinicians take these into account when prescribing this treatment.

If these types of chemotherapy were shown to impact sperm in some patients, this could have clinical implications on treatment plans and family planning.

Further research is required to investigate this at a deeper level before changing treatment for cancer in men. It is currently unclear why these types of chemotherapies seem to impact the sperm more than the egg cells.

Dr. Joanna Kaplanis, first author and Post-Doctoral Fellow at the Wellcome Sanger Institute, said: Hypermutation in children, where they have between two and seven times more random mutations than the general population, is rare and therefore cannot be caused by common carcinogens or exposures.

Our research analyses over 20,000 families and highlights new causes of these mutations, linking them back to germline mutations in the fathers sperm as well as identifying a new mutational signature.

Understanding the impact of these germline mutations in the sperm could help us uncover why some people are more likely to have children with these high rates ofrandom mutations, and help protect against these if they cause disease.

John Danesh, Director of HDR UK Cambridge, who supported the research, said, Hypermutation in children is an uncommon but important phenomenon that increases the risk of life-altering genetic diseases. By bringing together genetic data at scale, and linking this with routine clinical data like the hospital records of parents, the team has identified new risk factors that may influence future healthcare decisions.

This work elegantly demonstrates how work in Health Data Research UKs Understanding the Causes of Disease Programme is helping to link nationwidegenetic dataand clinical records in secure, anonymised and trustworthy ways that provide unique insights into unanticipated, but important questions.

Sir Mark Caulfield, from Queen Mary University of London, and former Chief Scientist at Genomics England, said: These findings were only possible due to access to whole genomes and linked health record data on the family members from the 100,000 Genomes Project. These findings could really help people with cancer consider family planning.

Professor Matthew Hurles, senior author and Head of Human Genetics at the Wellcome Sanger Institute, said: Chemotherapy is an incredibly effective treatment for many cancers, but unfortunately it can have some damaging side effects. Our research found a plausible link between two types of chemotherapy and their impact on sperm in a very small number of men.

These results require further systematic studies to see if there is acausal linkbetween chemotherapy and spermmutations, and if there is a way of identifying individuals at risk prior to treatment so they could takefamily planningmeasures, such as freezing their sperm prior to treatment.

I would also like to thank the families that donated their genetic and health information to make this research possible.

Author: Press OfficeSource: Wellcome Sanger InsituteContact: Press Office Wellcome Sanger InstituteImage: The image is in the public domain

Original Research: Open access.Genetic and chemotherapeutic influences on germline hypermutation by Matthew Hurles et al. Nature

Abstract

Genetic and chemotherapeutic influences on germline hypermutation

Mutations in the germline generates all evolutionary genetic variation and is a cause of genetic disease. Parental age is the primary determinant of the number of new germline mutations in an individuals genome.

Here we analysed the genome-wide sequences of 21,879 families with rare genetic diseases and identified 12 individuals with a hypermutated genome with between two and seven times more de novo single-nucleotide variants than expected. In most families (9 out of 12), the excess mutations came from the father.

Two families had genetic drivers of germline hypermutation, with fathers carrying damaging genetic variation in DNA-repair genes. For five of the families, paternal exposure to chemotherapeutic agents before conception was probably a key driver of hypermutation.

Our results suggest that the germline is well protected from mutagenic effects, hypermutation is rare, the number of excessmutations is relatively modest and most individuals with a hypermutated genome will not have a genetic disease.

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Increased Mutations in Children Can Be Traced Back to Mistakes in Father's Sperm - Neuroscience News

ByAnnika Weder

A nearly 40-year-old study is the basis for new groundbreaking collaborative research identifying the relationship between genetics, proteins, and disease risk, while shedding light on racial health disparities in the process.

The new study, the results of which have been published in a paper in Nature Genetics, has provided a wealth of information that will allow the research community to test the ways in which proteins affect health outcomes, such as the risk for developing various types of cancer or heart disease or contracting COVID-19. The work could also lead to the development or repurposing of therapeutic drugs to treat human disease. The researchers hope the study will increase the understanding of the genetic basis of disease, in particular because the diversity of study participants will unlock new information about the links between proteins and disease.

The makings of this comprehensive study date back to the mid-1980s, when the Atherosclerosis Risk in Communities study was launched with Josef Coresh from the Department of Epidemiology in the Bloomberg School of Public Health as a principal investigator. ARIC, for which Johns Hopkins is a key field center, investigated causes of atherosclerosisa disease characterized by the build-up of fats, cholesterol, and other substances in the walls of arteriesand measured how cardiovascular risk factors, medical care, and outcomes vary by race, sex, place, and time.

The study was notable in two critical ways: it followed individuals for decades, collecting biological samples at regular intervals; and it included Americans of European ancestry as well as Americans of African ancestry. Beginning in 1987, more than 10,000 participants regularly received physical examinations and follow-up phone calls to maintain contact and to assess the health status of the cohort. Data collected include participants' medical history, demographics, health behaviors, and genetic information. The ARIC study has become a valuable resource, resulting in over 2,500 publications to date. Many independent research projects have used ARIC data for a range of topics including the study of heart disease, kidney disease, diabetes, and cognitive decline.

When Nilanjan Chatterjee, Bloomberg Distinguished Professor of biostatistics and genetic epidemiology, learned through graduate students he was co-advising with Coresh that ARIC also collected participants' proteomic datainformation about the proteins present in organismshe realized the immense untapped potential this resource held.

Image caption: Nilanjan Chatterjee

Image credit: CHRIS HARTLOVE

Proteins have a central role in many biological functions, supporting the structure, function, regulation, and repair of organs, tissues, and cells. Proteins support muscle contraction and movement, for example. They transmit signals to coordinate processes between different organs and move essential molecules around the body. Antibodies that support immune function, hormones that help coordinate bodily function, and enzymes that carry out chemical reactions such as digestion are all proteins. Because proteins control many of the mechanisms critical to an organism's health, diseases can often trace their origins to mutations in proteins.

Proteomics, the systemic analysis of proteins, gathers information about the proteome, the complete set of proteins produced by a given cell, organ, or organism. It falls under a class of disciplines collectively referred to as omics, which aim to collectively characterize the groups of biological molecules that translate into the structure, function, and dynamics of an organism. Other examples of omics studies include genomics, the study of an organism's full genetic information; epigenomics, the study of the supporting structure of the genome; and transcriptomics, the study of the set of all RNA molecules.

"ARIC is an incredibly unique data source, both because of the amount of genetic, proteomic, and other omic data they have on such a large number of study individuals, and because of its inclusion of individuals from European and African ancestries," says Chatterjee. "Diverse ancestry data is completely lacking in many omics studies. ARIC had a wealth of proteomic data that had not been analyzed, so we were very happy to take advantage of this incredible resource available to us right here at Johns Hopkins."

For their study, the researchers first analyzed genetic variants that correlate with protein levels in individuals to identify protein quantitative trait loci, or pQTL, portion of DNA. They then developed machine learning-based models that can predict information about an individual's proteinsinformation that is not always collectedbased on genetic information, which is often more accessible in large-scale studies.

Nilanjan Chatterjee

Bloomberg Distinguished Professor of biostatistics and genetic epidemiology

This model in turn will allow scientists to identify links between the levels of certain proteins in an organism and its corresponding disease risk. Knowing which proteins to target in order to prevent development of a disease is crucial for developing new drug therapies or repurposing existing drug therapies, as many drugs work by targeting the body's proteins.

To demonstrate how the model works, the team applied it to proteome-wide association studies for two related traits: gout, a common form of arthritis, and its closely related biomarker, uric acid. The results showed that an existing drug could be repurposed to combat gout.

"'Omics' innovations have made multi-disciplinary collaborations necessary, exciting, and productive," says Coresh. "The lived experience of over 10,000 participants in the ARIC cohort, combined with data on nearly 5,000 protein levels in their blood, allowed for the development of tools that are broadly applicable to human health and disease. We have already seen more than a half a dozen new investigations using the tools and the methods will be even more broadly applicable."

For Chatterjee, the study's powerful models and insightful findings underlined the importance of using diverse populations in genetic and omics studies.

"African populations in particular have a lot more genetic variation because the population is older," Chatterjee says. "Excluding people of African ancestry means we miss out on a large fraction of genetic variations and how it impacts health outcomes. Taking results from a genome-wide association study done with only individuals of European ancestry and trying to apply the results to other populations does not work as well for understanding disease risk, which is not surprising. To best serve all patients, diversity in omics studies is imperative."

Josef Coresh

Epidemiologist and principal investigator on the ARIC study

In addition, the team found that information garnered from populations of African ancestry added incredible value for interpreting results from study participants overall.

"Because European populations are newer, their genes are more confoundedmany variants always come together, and it is difficult to determine which genetic variant is causally related to a trait," Chatterjee explains. "African populations are older, and over more generations, the tight linkage among variants have broken down and it becomes possible to identify which variants are most likely to be the causal variant for a trait."

Looking forward, for Chatterjee, an exciting aspect of this project was the immense potential for impact these models have. Chatterjee hopes that a multi-omics approach in a multi-ancestry study will unlock a more comprehensive understanding of the genetic basis of complex disease and how that genetic basis arises. Next steps may include developing and improving statistical and machine learning models to combine data from populations of multiple ancestries, data from other types of -omics studies, and extending analysis to rare variants.

The authors emphasize that the study would not be possible without the strong partnerships and collaborations across Johns Hopkins and beyond, including the sophisticated data analysis led by Department of Biostatistics PhD student Jingning Zhang and post-doctoral fellow Diptavo Dutta.

Given the collaborative nature of the undertaking, it was important to the team to make the resources and models they developed available to others. They have made the models available online.

"Anyone can download these models for use in their own study to test for the effect of proteins on whichever traits they are investigating," Chatterjee explains. "Our work has already generated ideas for many follow-up studies using proteomic data, and it has been exciting to see that, in fact, people have already started using the models in their own protein association studies."

Read more from the original source:
Study probes the relationship between genetics, proteins, and disease risk - The Hub at Johns Hopkins

In 1996, Dolly the sheep made headlines around the world after becoming the first mammal to be successfully cloned from an adult cell. Many commentators thought this would catalyze a golden age of cloning, with numerous voices speculating that the first human clone must surely be just a few years away.

Some people suggested that human clones could play a role in eradicating genetic diseases, while others considered that the cloning process could, eventually, eliminate birth defects (despite research by a group of French scientists in 1999 finding that cloning may actually increase the risk of birth defects).

There have been various claims all unfounded, it is important to add of successful human cloning progams since the success of Dolly. In 2002, Brigitte Boisselier, a French chemist and devout supporter of Ralism a UFO religion based on the idea that aliens created humanity claimed that she and a team of scientists had successfully delivered the first cloned human, whom she named Eve.

However, Boisselier was unwilling or indeed unable to provide any evidence, and so it is widely believed to be a hoax.

So why, almost 30 years on from Dolly, haven't humans been cloned yet? Is it primarily for ethical reasons, are there technological barriers, or is it simply not worth doing?

Related: What are the alternatives to animal testing?

"Cloning" is a broad term, given it can be used to describe a range of processes and approaches, but the aim is always to produce "genetically identical copies of a biological entity," according to the National Human Genome Research Institute (NHGRI).

Any attempted human cloning would most likely utilize "reproductive cloning" techniques an approach in which a "mature somatic cell," most probably a skin cell, would be used, according to NHGRI. The DNA extracted from this cell would be placed into the egg cell of a donor that has "had its own DNA-containing nucleus removed."

The egg would then begin to develop in a test tube before being "implanted into the womb of an adult female," according to NHGRI.

However, while scientists have cloned many mammals, including cattle, goats, rabbits and cats, humans have not made the list.

"I think there is no good reason to make [human] clones," Hank Greely, a professor of law and genetics at Stanford University who specializes in ethical, legal and social issues arising from advances in the biosciences, told Live Science in an email.

"Human cloning is a particularly dramatic action, and was one of the topics that helped launch American bioethics," Greely added.

The ethical concerns around human cloning are many and varied. According to Britannica, the potential issues encompass "psychological, social and physiological risks." These include the idea that cloning could lead to a "very high likelihood" of loss of life, as well as concerns around cloning being used by supporters of eugenics. Furthermore, according to Britannica, cloning could be deemed to violate "principles of human dignity, freedom and equality."

In addition, the cloning of mammals has historically resulted in extremely high rates of death and developmental abnormalities in the clones, Live Science previously reported.

Another core issue with human cloning is that, rather than creating a carbon copy of the original person, it would produce an individual with their own thoughts and opinions.

"We've all known clones identical twins are clones of each other and thus we all know that clones aren't the same person," Greely explained.

A human clone, Greely continued, would only have the same genetic makeup as someone else they would not share other things such as personality, morals or sense of humor: these would be unique to both parties.

People are, as we well know, far more than simply a product of their DNA. While it is possible to reproduce genetic material, it is not possible to exactly replicate living environments, create an identical upbringing, or have two people encounter the same life experiences.

So, if scientists were to clone a human, would there be any benefits, scientific or otherwise?

"There are none that we should be willing to consider," Greely said, emphasizing that the ethical concerns would be impossible to overlook.

However, if moral considerations were removed entirely from the equation, then "one theoretical benefit would be to create genetically identical humans for research purposes," Greely said, though he was keen to reaffirm his view that this should be thought of as "an ethical non-starter."

Greely also stated that, regardless of his own personal opinion, some of the potential benefits associated with cloning humans have, to a certain degree, been made redundant by other scientific developments.

"The idea of using cloned embryos for purposes other than making babies, for example producing human embryonic stem cells identical to a donor's cells, was widely discussed in the early 2000s," he said, but this line of research became irrelevant and has subsequently not been expanded upon post-2006, the year so-called induced pluripotent stem cells (iPSCs) were discovered. These are "adult" cells that have been reprogrammed to resemble cells in early development.

Shinya Yamanaka, a Japanese stem cell researcher and 2012 Nobel Prize winner, made the discovery when he "worked out how to return adult mouse cells to an embryonic-like state using just four genetic factors," according to an article in Nature. The following year, Yamanaka, alongside renowned American biologist James Thompson, managed to do the same with human cells.

When iPSCs are "reprogrammed back into an embryonic-like pluripotent state," they enable the "development of an unlimited source of any type of human cell needed for therapeutic purposes," according to the Center of Regenerative Medicine and Stem Cell Research at the University of California, Los Angeles.

Therefore, instead of using embryos, "we can effectively do the same thing with skin cells," Greely said.

This development in iPSC technology essentially rendered the concept of using cloned embryos both unnecessary and scientifically inferior.

Related: What is the most genetically diverse species?

Nowadays, iPSCs can be used for research in disease modeling, medicinal drug discovery and regenerative medicine, according to a 2015 paper published in the journal Frontiers in Cell and Developmental Biology.

Additionally, Greely also suggested that human cloning may simply no longer be a "sexy" area of scientific study, which could also explain why it has seen very little development in recent years.

He pointed out that human germline genome editing is now a more interesting topic in the public's mind, with many curious about the concept of creating "super babies," for example. Germline editing, or germline engineering, is a process, or series of processes, that create permanent changes to an individuals genome. These alterations, when introduced effectively, become heritable, meaning they will be handed down from parent to child.

Such editing is controversial and yet to be fully understood. In 2018, the Council of Europe Committee on Bioethics, which represents 47 European states, released a statement saying that "ethics and human rights must guide any use of genome editing technologies in human beings," adding that "the application of genome editing technologies to human embryos raises many ethical, social and safety issues, particularly from any modification of the human genome which could be passed on to future generations."

However, the council also noted that there is "strong support" for using such engineering and editing technologies to better understand "the causes of diseases and their future treatment," noting that they offer "considerable potential for research in this field and to improve human health."

George Church, a geneticist and molecular engineer at Harvard University, supports Greely's assertion that germline editing is likely to garner more scientific interest in the future, especially when compared with "conventional" cloning.

"Cloning-based germline editing is typically more precise, can involve more genes, and has more efficient delivery to all cells than somatic genome editing," he told Live Science.

However, Church was keen to urge caution, and admitted that such editing has not yet been mastered.

"Potential drawbacks to address include safety, efficacy and equitable access for all," he concluded.

Originally published on Live Science.

The rest is here:
Why haven't we cloned a human yet? - Livescience.com

The authors of a major study on the once critically endangered pink pigeon say boosting the species numbers is not enough to save it from extinction in the future.

Despite the population increase, the teams analysis shows the pink pigeon has a high genetic load of bad mutations, which puts it at considerable risk of extinction in the wild within 100 years without continued conservation actions.

An international collaboration led by scientists from the University of East Anglia (UEA), Durrell Institute of Conservation and Ecology (DICE) at the University of Kent and the Earlham Institute in the UK, working with organisations on the ground in Mauritius, investigated the genetic impacts of a population bottleneck a rapid collapse in numbers that affected the pink pigeon from Mauritius in the late 1980s, with only 12 birds surviving in the wild.

The team analysed the DNA of 175 birds sampled over nearly 20 years as subsequent conservation efforts took place.

With the help of biologists from the Mauritian Wildlife Foundation and the Durrell Wildlife Conservation Trust, and in partnership with the Government of Mauritius National Parks and Conservation Service, the free-living population of the species has increased to around 500 birds.

Consequently, the pink pigeon has been down-listed twice on the International Union for Conservation of Nature Red List from critically endangered to vulnerable.

However, to keep these populations viable, the researchers warn that genetic rescue is needed to recover lost genetic variation caused by inbreeding and to reduce the effects of the harmful mutations. This can be achieved by releasing captive-bred birds from UK and EU zoos.

The study, published inConservation Biology, used conservation genetic work at DICE, cutting-edge genomic techniques developed at UEA and the Earlham Institute, and computer modelling to closely examine the species DNA and assess the risk of future extinction, as well as forecasting what needs to be done to secure the pink pigeons viability. The authors say their findings could help other threatened species.

By studying the genome of a recovered species that was once critically endangered, we can learn how to help other species to bounce back from a population collapse, said UEAs Prof Cock van Oosterhout, one of the lead authors.

During the pigeons population bottleneck, the gene pool lost a lot of variation, and many bad mutations increased in frequency. This genetic load still poses a severe threat, even though the population has recovered in numbers.

Prof van Oosterhout, of the School of Environmental Sciences at UEA, added: The problem is that all individuals are somehow related to each other. They are the descendants of the few ancestors that managed to survive the bottleneck. Hence, it becomes virtually impossible to stop inbreeding, and this exposes these bad mutations. In turn, this can increase the mortality rate, and it could cause the population to collapse again.

Prof Jim Groombridge, from the University of Kent, explained how the initial recovery of the pink pigeon population was achieved: A captive population of pink pigeons in the Gerald Durrell Endemic Wildlife Sanctuary in Mauritius, jointly managed by the Mauritian Wildlife Foundation and the National Parks and Conservation Service, was established in the 1970s.

This was used to breed birds for release into the wild, which boosted population numbers. The team also restored habitat by controlling introduced species and provided supplementary food as part of a field programme of intensive conservation management, which further increased the free-living population.

The study used sophisticated software called SLiM that can model an entire bird chromosome, including all its bad mutations. The researchers simulated the bottleneck and population recovery, and then they compared the predicted outcomes of different reintroduction programmes. The study was therefore able to predict the viability of the population in the future under different conservation management scenarios.

We didnt know how many bad mutations the population carried initially, before the bottleneck, said Dr Hernan Morales from University of Copenhagen, in Denmark, who performed the SLiM modelling. We first had to simulate the ancestral population to find out how many bad mutations could have evolved. We then checked this data with data on inbreeding depression data from zoo populations of the pink pigeon.

Using pedigree and fitness data held at Jersey Zoo for over 1000 birds, the team estimated the genetic load, which showed that the pink pigeon carried a high genetic load of 15 lethal equivalents. This was then used to calibrate the computer models.

The computer simulations clearly show that just boosting numbers isnt enough, added Dr Morales. The population also needs genetic rescue from more genetically diverse birds bred in European zoos. These birds are not as closely related, and they can help to reduce the level of inbreeding. However, there is a risk that we could introduce other bad mutations from the zoo population into the wild.

Dr Camilla Ryan, who worked on the project at the Earlham Institute and UEA, said: Our bioinformatics analysis indicated the importance of genetic diversity and the uniquegenetic rescuemodel to help other species from the brink of extinction. This research highlights the value of collaborations between NGOs, institutes and universities which draw together a range of expertise. This ensures that a holistic approach is taken to a species conservation which includes an understanding of its genetic health.

Sam Speak, a PhD student at UEA and co-author of the paper, added: We are now analysing the genome of the pink pigeon from zoo populations here in the UK, trying to locate these bad mutations. We can do this now using bioinformatics tools developed for studying human genetics and the genomes of other model bird species such as the chicken.

By using conservation genomics, future reintroduction programmes can avoid releasing individuals with high genetic load. This would help reduce inbreeding and improve the long-term recovery of threatened species such as the pink pigeon.

More here:
Not All Is Rosy For The Pink Pigeon - Eurasia Review

LA JOLLA, Calif., May 10, 2022 (GLOBE NEWSWIRE) -- Singular Genomics Systems, Inc. (Nasdaq: OMIC), a company leveraging novel next-generation sequencing (NGS) and multiomics technologies to empower researchers and clinicians, today announced the formation of its scientific advisory board (SAB). The SAB comprises a distinguished group of academic and industry experts who will advise on the companys product and service offerings and research and development pipeline.

We are pleased to announce the launch of our scientific advisory board and are privileged to work with such accomplished leaders in science and medicine, said Eli Glezer, Ph.D., Founder and Chief Scientific Officer of Singular Genomics and newly appointed Chair of the SAB. This groups expertise in DNA sequencing, human genetics, oncology and immunology will be an invaluable resource as we expand the applications of our G4 sequencing system and develop the PX platform as a powerful tool for spatial biology.

The members of Singulars SAB include:

About Singular Genomics Systems, Inc. Singular Genomics is a life science technology company that is leveraging novel NGS and multiomics technologies to build products that empower researchers and clinicians. Our mission is to accelerate genomics for the advancement of science and medicine. Our Singular Sequencing Engine is the foundational platform technology that forms the basis of our products as well as our core product tenets: power, speed, flexibility and accuracy. We are currently developing two products that are purpose-built to target applications in which these core product tenets matter most. Our first product, the G4, targets the NGS market. Our second product in development, the PX, combines single-cell analysis, spatial analysis, genomics and proteomics in one integrated instrument to offer a versatile multiomics solution.

Forward-Looking Statements Certain statements contained in this press release, other than historical information, may constitute forward-looking statements within the meaning of the Federal securities laws. Any such forward-looking statements are based on our managements current expectations and are subject to a number of risks and uncertainties that could cause our actual future results to differ materially from our managements current expectations or those implied by the forward-looking statements. These and other risk factors that may affect our future results of operations are identified and described in more detail in our most recent filings on Forms 10-K and 10-Q and in other filings that we make with the SEC from time to time, including our Quarterly Report on Form 10-Q for period ended March 31, 2022, filed with the SEC on May 10, 2022. Accordingly, you should not rely upon forward-looking statements as predictions of future events or our future performance. Except as required by applicable law, we undertake no obligation to update publicly or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise.

Investor ContactMatt Clawson949-370-8500ir@singulargenomics.com

Media ContactDan Budwick, 1AB973-271-6085dan@1abmedia.com

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Singular Genomics Announces Formation of Scientific Advisory Board - BioSpace

A small demographic may have the key to better understanding how humans are at risk for a COVID-19 infection. Scientists are now looking into a group of people who never contracted the novel coronavirus throughout the pandemic despite the emergence of more transmissible variants.

Around one in ten people in England seemingly have some sort of resistance to COVID-19 because they never caught the virus since the pandemic started. Because of this, scientists are eager to know if this group of people could lead them to a potential cure for the disease.

A study launched late last year introduced a global effort to dissect the human genetic basis of resistance to the life-threatening disease caused by SARS-CoV-2. The team behind it proposed a strategy to determine, recruit and genetically analyze the people who showed natural resistance to COVID-19 infection.

The researchers noted that several candidate genes could be involved in providing inborn resistance to COVID-19 in certain individuals. By understanding them, the team could identify mechanisms that possibly restrict viral replication and promote resilience upon infection.

What we are looking for is potentially very rare genetics variants with a very big impact on the individual, lead researcher Andrs Spaan, a clinical microbiologist from the Rockefeller University in New York, told The Washington Post.

The international study already has 700 participants. More than 5,000 people believed to also be immune to the virus are also being screened by the scientists for the research.

There is a theory that some people may have not contracted COVID-19 due to fewer receptors in their noses, throats, and lungs, making it difficult for the coronavirus to bind and cause an infection. This was brought up because there were health workers who did not wear face masks at the peak of the pandemic and still tested negative for COVID every week.

There is also a possibility that the same group of people might have been previously exposed to a similar virus that gave their immune systems a boost and protection against SARS-CoV-2, as per HuffPost.

For the international study, the team is more focused on uncovering if some people were born with a particular immune system armed with the right genetic materials to combat SARS-CoV-2. Finding answers to this could help the medical community better deal with the situation and come up with the right drugs to counter the virus and its newer strains.

Read more:
COVID Resistance Might Be Tied To Genetics: Experts - Medical Daily

Ive been reading the many recent letters regarding the likely reversal of Roe v. Wade. The writer of The case for overturning Roe v Wade has it right by pointing out that there is absolutely nothing in the U.S. Constitution that provides for a right to abortion. The writer however said he was pro-choice, stating that one of the reasons for this was the small size of the unborn baby at the time of most abortions. But of course we were all small during those first several months in our mothers womb, and yet our complete human genetics were already set from the moment of conception.

The writer also said that women should have absolute bodily autonomy, again intentionally ignoring the absolute scientific fact that theres another body involved - that of her not yet born little girl or boy. We keep hearing follow the science, but when the science shows 100% that unique human life begins at conception, abortion supporters pretend science doesnt matter here.

Another writer mistakenly took it upon himself to be able to look into everyone elses hearts and minds and decide that Its about control, not babies . By this he meant people trying to control women. While I dont have the ability to judge others like that writer, I do know from years of working with pro-life that it is about both protecting unborn babies, and offering life-options help to women. Thankfully, I found one point of agreement in his letter, that being that God still loves those who choose abortion. Such merciful love provides forgiveness and restoration for those who repent and receive it.

Several writers blamed the Catholic Church for Roes reversal. While Catholics have been at the forefront working to restore protection for innocent human life in the womb; be assured that there are also tens of millions of other-than-Catholics who are working and praying for this as well.

Also, we keep hearing of the need for abortions to be legal and safe. Well, as pointed out above, legal abortions certainly arent safe for the 50% of the human lives involved who are killed by abortion. In addition, many of the legal abortions arent physically safe for the mother as well. And, they certainly arent safe emotionally, as there is often a lifetime of guilt to deal with.

The bottom line is that intentionally killing innocent human life is most certainly not reproductive health care. Rather, we need to continue to support women who find themselves in an unexpected pregnancy - as is being done with the ever increasing number of pregnancy help centers and homes, church programs and adoption options. Where there is genuine medical need during a pregnancy, there is help available to protect both the life of the mother and her unborn.

Finally, as another writer pointed out, its way past time to stop pretending otherwise - abortion ends the life of a unique and innocent human being! Every human life conceived is a gift of God, created in his image. May we all say no to Roe and yes to life!

Ken Koehler lives in West Fargo.

This letter does not necessarily reflect the opinion of The Forum's editorial board nor Forum ownership.

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Letter: Why no to Roe and abortion - INFORUM

SEATTLE--(BUSINESS WIRE)--More than 40 million Americans take statins, the most common type of prescription drug. While statins have been shown to effectively lower cholesterol levels and reduce the risks of stroke and heart attack, they do not work the same for everyone, and side effects of statin use include an increased risk of developing type 2 diabetes.

Researchers from Institute for Systems Biology have shown that different patient responses to statins can be explained by the variation in the human microbiome. The findings were published today in the journal Med, and offer promising avenues for optimizing precision statin treatments for individual patients.

The research team found that the composition and diversity of the gut microbiome is predictive of the efficacy of statins and the magnitude of negative side effects.

Specifically, we found that a Bacteroides enriched microbiome with lower levels of diversity was associated with the strongest LDL-lowering response to statins, but also coincided with the greatest disruption to blood glucose levels, said Dr. Tomasz Wilmanski, lead author of the study.

The team also found that individuals with a Ruminococcaceae enriched microbiome were protected from the negative side effects of statins on insulin resistance while also showing a clear LDL-lowering response.

Wimanski and his colleagues built statistical models with microbiome, metabolome, human genome, and clinical records from an American cohort of more than 1,800 people and made their initial discoveries about variable statin effects on both cholesterol and blood glucose markers. Next, they validated their results in an independent European cohort of nearly 1,000 people.

The unique combination of microbiome and genomic information in this study provides exciting new insights into potential approaches to precision drug treatments.

The genetic fingerprint of a patient, which includes known genetic markers of statin treatment response, has already been leveraged in the clinic to guide personalized statin treatment regimes. In this study, the authors found that the variability in statin responses explained by the microbiome were completely independent of the variability captured by the genome. Its a completely different axis of variability, so were able to build models including both genetics and the gut microbiome to improve our statin response predictions, Wilmanski said. The genome and the microbiome, together, appear to provide a more comprehensive and complementary picture of personalized drug responses.

A logical follow-up to this work is a clinical trial. It would be great to take this knowledge about the genome and the microbiome and predict personalized dosing regimens for a cohort of patients, and then follow these patients forward in time, tracking their metabolic health and their LDL cholesterol levels, to show that this population of patients undergoing a precision intervention do better than a control group of patients who are getting what is normally prescribed, said ISB Assistant Professor Dr. Sean Gibbons, a corresponding author on the paper.

About ISB

Institute for Systems Biology (ISB) is a Seattle-based non-profit biomedical research organization. We focus on some of the most pressing issues in human health, including aging, brain health, cancer, COVID-19, and many infectious diseases. ISB is an affiliate of Providence, one of the nations largest not-for-profit health care systems. Follow us at http://www.isbscience.org and on YouTube, Facebook, LinkedIn and Twitter.

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Gut Microbiome Composition Predictive of Patient Response to Statins - Business Wire

Texas A&M senior biology major Annabel Perry 22 is graduating with a bachelor of science in biology.

Courtesy photo

Every picture tells a story. One of Annabel Perrys childhood favorites features her as a grinning 10-year-old clutching a gigantic bullfrog, a slightly out-of-focus snapshot of both place and time that captures her budding interest in the natural world and her future as a scientist a career path and underlying passion accelerated by undergraduate research and key faculty mentors at Texas A&M University.

This little girl with the bullfrog, however, didnt start out with all the tools she needed to succeed as a scientist. Perry, who was homeschooled as a child in Milford, Texas, grew up believing that women were less logical than men, evolution was not real and human behaviors were not biologically determined. She didnt seriously question those beliefs until, at the age of 16 after researching disordered eating in a dual-credit course, she realized she had a serious eating disorder an awakening that not only propelled Perry to seek professional mental health treatment, but also instilled in her a desire to understand the biological underpinnings of psychiatric disorders.

This early experience with mental health care taught me that science can explain behavior and improve lives, Perry said. So, in fall 2018, I entered Texas A&M University with a plan to scientifically study psychiatric disorders. Experiences at Texas A&M and beyond developed this curiosity into a passion for cognitive evolution and showed me there is a place in the world of science for the little girl with the bullfrog.

Although Perry had planned to research disordered eating as a freshman at Texas A&M, she found no professors working on the topic. However, she soon discovered an intriguing alternative in Texas A&M psychologist and neuroscientistBrian Andersons laboratory, which explores how reward and punishment influence learning and attention.

In this lab, I monitored an automated shock machine and recorded results as human subjects completed attention-intensive tasks, Perry said. During the course of such work, I discovered that I am interested not only in psychiatric disorders, but in all manner of cognitive traits.

Perry at age 10.

Courtesy photo

Because Perrys interest extended far beyond the proximate causes of behavior, she enrolled in Texas A&M biologistDuncan MacKenzies honors freshman biology course. In addition to learning about evolution for the first time, she says she fell in love with the interconnected mechanisms, puzzle-solving and predictive power of evolutionary theory and wanted to pursue that passion by researching evolution.

I particularly wanted to research the evolution of sex differences, as Id been raised on stereotypes about cognitive differences between the sexes and wanted to learn their biological truth, Perry said. So I joined Texas A&M biologistGil Rosenthals laboratory, which studies sexual selection and mating behavior in swordtail fish.

After learning to use the labs tracking software used to study sex differences in swordtails, Perry realized that computational skills would be integral to her success as an evolutionary biologist. When the COVID-19 pandemic forced the Rosenthal lab to work from home, Rosenthal encouraged all members to begin learning the Python coding language. Rosenthal recognized Perrys potential as a computational biologist and asked her to spearhead a bioinformatics project to detect variable DNA regions in hybrid swordtail fish.

I took this opportunity to prove to the little girl with the bullfrog that gender does not determine her analytic ability, Perry said. I spent summer 2020 teaching myself R and C++. Since there was no existing program that could detect the DNA regions, I taught myself R to create my own. But R could not process such large data, so I taught myself the more robust but notoriously daunting language C++. The C++ version of my program, Polly, ran successfully but categorized the wrong regions as polymorphic. So, I fixed Polly, getting it to correctly detect these regions in February 2021.

Bolstered by her burgeoning confidence in both coding and research, Perry excelled in graduate-level courses on experimental design and evolution as a junior and senior, respectively. In addition to beginning another C++ program for calculating linkage disequilibrium scores, she was accepted into a summer 2021National Science Foundation Research Experiences for Undergraduates (REU) programat Florida Atlantic University. As fate would have it, she worked with Erik Dubou andAlex Keene who coincidentally accepted a new position as head of theTexas A&M Department of Biologywhile she was in Florida to study the evolution of anxiety in cavefish. Together, they developed a computational neural network for classifying behaviors and used it to quantify anxiety in the Mexican tetra model organism.

During this project, I was simultaneously making Polly more biologist-friendly by making it accessible through an easier-to-use coding language, Perry said. By the end of summer 2021, I finished both the REU and Polly projects. I am first author on the Polly manuscript, which is currently under peer review atMolecular Ecology Resources.

By the time Perry returned to Texas A&M for her senior year in August, Rosenthal had moved to Italy, and Keene had begun his appointment as head of Texas A&M Biology. While simultaneously completing her Rosenthal lab projects remotely, Perry began conducting anUndergraduate Research Scholars thesiswith Keene and fellow Texas A&M biologist/computational evolutionary geneticistHeath Blackmonas one of the College of Sciences 12 inauguralScience Undergraduate Research Opportunities Program (SUROP)awardees. For this project, she coded a web-based tool, dubbedCaveCrawler, to analyze genetics data in the Mexican tetra, an emerging model system to study the evolution of sleep and potentially many other cognitive and physiological traits. A preprint of the resulting publication, CaveCrawler: An interactive analysis suite for cavefish bioinformatics, was uploaded to the open access repositorybioRXivin December and since has been accepted for publication by the Genetics Society of America journalG3: Genes | Genomes | Genetics.

Annabel is remarkably talented, and her productivity was at the level of a senior graduate student, Keene said. What really sets her apart is her enthusiasm for science and her ability to elevate everyone around her.

In between semesters in January, Perry traveled to central Mexico to conduct field research with Rosenthal and fellow swordtail lab members at the Centro de lnvestigaciones Cientificas de las Huastecas Aguazarca, also known asCICHAZ. Roughly a month later, she was the only undergraduate who presented her research at the7th annual Cavefish Meeting, held February 27-March 4 in San Antonio. She also presented on her research and life-changing undergraduate experience at the April 1 College of Science External Advisory and Development Council spring meeting.

On Saturday (May 14), Perry will graduate from Texas A&M with her bachelor of science in biology with honors along with double minors in neuroscience and philosophy. In addition to being recognized as a University Scholar, Undergraduate Research Scholar and Honors Fellow, she was a finalist for the 2022 Brown Foundation-Earl Rudder Memorial Outstanding Student Award honoring the top graduating seniors across the entire Texas A&M campus. This fall, she will head to Harvard University to pursue her Ph.D. working withDavid Reich in the Department of Human Evolutionary Biology,

Working with someone like Annabel could rekindle anyones enthusiasm for science, Rosenthal said. When the pandemic hit, we did a weekly Python workshop as a lab over zoom. We went through the wonderful Rosalind website, which presents every new technique as a puzzle. She left the rest of us in the dust as she solved each puzzle with ever-growing enthusiasm, till she was out of puzzles that other people had already solved. Now shes applying her full intellect and creativity to problems no one knows the answer to. Her infectious curiosity and her intellectual humility are just what Harvard needs.

As she prepares to walk the Reed Arena stage, Perry says she is not only grateful for being able to stand on the shoulders of many, including her mentors at Texas A&M, but also eager to pay those opportunities forward to benefit other aspiring scientists in the making.

A neuroscientists job is not just to investigate the innerworkings of the human brain, but also to help other people realize the power of their own minds, Perry said. In graduate school, I plan to start coding workshops for rural children. My eventual goal is to run my own lab where I mentor budding young scientists and use computational approaches to research cognitive evolution. Once I have my own lab, I will continue this mentorship to show them that they, like the little girl with the bullfrog, can achieve their intellectual potential.

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Finding A Place In Science - Texas A&M Today - Texas A&M University Today

New Delhi: Vineeta Agarwala, the wife of Twitter CEO Parag Agrawal, is now making headlines amid Elon Musks $44 billion takeover deal.

Her role as general partner at Andreessen Horowitz (a16z) a top US VC firm which has agreed to pay $400 million as part of Musks new $7.1 billion financing commitments is set to create a conflict of interest.

As a general partner at Andreessen Horowitz, she leads investments for the firms bio and health fund across therapeutics, life sciences tools/diagnostics, and digital health, with a focus on companies leveraging unique datasets to improve drug development and patient care delivery.

Andreessen Horowitz is also one of the biggest backers of Facebook (now Meta).

Prior to joining a16z, Vineeta held many different roles in the healthcare space.

She was a physician taking care of patients, an operator at health tech startups and as a venture investor on the Google Ventures life sciences team.

She was an early data scientist at Kyruus, a management consultant for biotech, pharmaceutical, and medical device clients at McKinsey & Co; and a director of product management at Flatiron Health.

She has collaborated with academic researchers at Cold Spring Harbor Laboratory, Lawrence Livermore National Laboratory, and the Broad Institute, where she did graduate work in computational biology and human genetics.

Vineeta holds a Bachelor of Science in biophysics from Stanford University, and MD and PhD degrees from Harvard Medical School/MIT.

She continues to see patients at Stanford as an adjunct clinical professor in the Division of Primary Care and Population Health.

Vineeta serves on a number of portfolio company boards, including BigHat Biosciences, GC Therapeutics, Memora Health, Thyme Care, Pearl Health, and Waymark.

Parag studied BTech in Computer Science and Engineering at IIT Bombay and completed his PhD from Stanford University.

They have a son named Ansh and the couple is based in San Francisco, California.

Meanwhile, there are doubts over Parags future once Musk takes over, as the Tesla CEO himself can become a temporary CEO of the platform. According to reports, Musk may have also lined up a new Twitter CEO.

Parag is likely to receive nearly $39 million due to a clause in his contract once he leaves Twitter. His total compensation for 2021 was $30.4 million, largely in stocks.

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Parag Agrawals wife Vineeta linked with Musks Twitter takeover - The Siasat Daily