Category Archives: Genetics

Many variants in the human genome have been linked to type 2 diabetes, but because most do not lie within genes that code for proteins, its unclear how they might cause disease. Now an international team, including investigators at Massachusetts General Hospital (MGH), has developed a resource to help uncover the impact of these genetic variants.

The work, which is described inCell Reports, relies on the knolwedge that abnormalities in groups of pancreatic cells called islets, which produce and release hormones that regulate blood sugar levels, drive the development of type 2 diabetes. Unfortunately, however, its very difficult to obtain samples of human islets. To overcome this challenge, scientists from Spain, Belgium, Italy, Sweden, Finland, the UK, and the US banded together to obtain more than 500 human islet samples from patients with and without type 2 diabetes and to extract genomic and gene expression data from these samples. With these data, the researchers created what they named TIGER (for Translational human pancreatic Islet Genotype tissue-Expression Resource).

The research required collecting and examining an enormous amount of information, which was made possible through the use of supercomputing resources and new statistical methods.

Analyses of TIGER revealed that certain genetic variants in islets from patients with type 2 diabetes control the expression of particular genes. So far, 32 novel genes were identified that may contribute to type 2 diabetes risk.

This resource will be very useful to identify genes that may be related with the genetic variants that we have found associated with type 2 diabetes, says cosenior author Josep M. Mercader, PhD, a research-scientist at MGHs Diabetes Unit and Center for Genomic Medicine. Knowing the gene behind a given genetic association is the first step for identifyingpotential drug targets, or to better understand the physiology of different types of diabetes.

TIGERs data are publicly available and easily accessible to the diabetes research community through the TIGER web portal (tiger.bsc.es).

We are proud that we are now able to share this wealth of data to the scientific community in an easily accessible way for all researchers in the type 2 diabetes field, without the need of computational or bioinformatic expertise, says colead author Lorena Alonso, of the Barcelona Supercomputing Center, in Spain, one of the developers of the TIGER portal.

Reference: Alonso L, Piron A,Moran A et al. TIGER: The gene expression regulatory variation landscape of human pancreatic islets. Cell Reports. 2021. doi:10.1016/j.celrep.2021.109807.

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New Resource Will Drive Research on the Genetics of Type 2 Diabetes - Technology Networks

A little over a decade ago, a clutch of scientific studies was published that seemed to show that survivors of atrocities or disasters such as the Holocaust and the Dutch famine of 1944-45 had passed on the biological scars of those traumatic experiences to their children.

The studies caused a sensation, earning their own BBC Horizon documentary and the cover of Time (I also wrote about them, for New Scientist) and no wonder. The mind-blowing implications were that DNA wasnt the only mode of biological inheritance, and that traits acquired by a person in their lifetime could be heritable. Since we receive our full complement of genes at conception and it remains essentially unchanged until our death, this information was thought to be transmitted via chemical tags on genes called epigenetic marks that dial those genes output up or down. The phenomenon, known as transgenerational epigenetic inheritance, caught the public imagination, in part because it seemed to release us from the tyranny of DNA. Genetic determinism was dead.

A decade on, the case for transgenerational epigenetic inheritance in humans has crumbled. Scientists know that it happens in plants, and weakly in some mammals. They cant rule it out in people, because its difficult to rule anything out in science, but there is no convincing evidence for it to date and no known physiological mechanism by which it could work. One well documented finding alone seems to present a towering obstacle to it: except in very rare genetic disorders, all epigenetic marks are erased from the genetic material of a human egg and sperm soon after their nuclei fuse during fertilisation. The [epigenetic] patterns are established anew in each generation, says geneticist Bernhard Horsthemke of the University of Duisburg-Essen in Germany.

Even at the time, sceptics pointed out that it was fiendishly difficult to disentangle the genetic, epigenetic and environmental contributions to inherited traits. For one thing, a person shares her mothers environment from the womb on, so that persons epigenome could come to resemble her mothers without any information being transmitted via the germline, or reproductive cells. In the past decade, the threads have become even more tangled, because it turns out that epigenetic marks are themselves largely under genetic control. Some genes influence the degree to which other genes are annotated and this shows up in twin studies, where certain epigenetic patterns have been found to be more similar in identical twins that in non-identical ones.

This has led researchers to think of the epigenome less as the language in which the environment commands the genes, and more as a way in which the genes adjust themselves to respond better to an unpredictable environment. Epigenetics is often presented as being in opposition to genetics, but actually the two things are intertwined, says Jonathan Mill, an epigeneticist at the University of Exeter. The relationship between them is still being worked out, but for geneticist Adrian Bird of the University of Edinburgh, the role of the environment in shaping the epigenome has been exaggerated. In fact, cells go to quite a lot of trouble to insulate themselves from environmental insult, he says.

Whatever that relationship turns out to be, the study of epigenetics seems to reinforce the case that its not nature versus nurture, but nature plus nurture (so genetic determinism is still dead). And whatever the contribution of the epigenome, it doesnt seem to translate across generations.

All the aforementioned researchers rue the fact that transgenerational epigenetic inheritance is still what most people think of when they hear the word epigenetics, because the past decade has also seen exciting advances in the field, in terms of the light it has shed on human health and disease. The marks that accumulate on somatic cells that is, all the bodys cells except the reproductive ones turn out to be very informative about these, and new technologies have made it easier to read them.

Different people define epigenetics differently, which is another reason why the field is misunderstood. Some define it as modifications to chromatin, the package that contains DNA inside the nuclei of human cells, while others include modifications to RNA. DNA is modified by the addition of chemical groups. Methylation, when a methyl group is added, is the form of DNA modification that has been studied most, but DNA can also be tagged with hydroxymethyl groups, and proteins in the chromatin complex can be modified too.

Researchers can generate genome-wide maps of DNA methylation and use these to track biological ageing, which as everyone knows is not the same as chronological ageing. The first such epigenetic clocks were established for blood, and showed strong associations with other measures of blood ageing such as blood pressure and lipid levels. But the epigenetic signature of ageing is different in different tissues, so these couldnt tell you much about, say, brain or liver. The past five years have seen the description of many more tissue-specific epigenetic clocks.

Mills group is working on a brain clock, for example, that he hopes will correlate with other indicators of ageing in the cortex. He has already identified what he believes to be an epigenetic signature of neurodegenerative disease. Were able to show robust differences in DNA methylation between individuals with and without dementia, that are very strongly related to the amount of pathology they have in their brains, Mill says. Its not yet possible to say whether those differences are a cause or consequence of the pathology, but they provide information about the mechanisms and genes that are disrupted in the disease process, that could guide the development of novel diagnostic tests and treatments. If a signal could be found in the blood, say, that correlated with the brain signal theyve detected, it could form the basis of a predictive blood test for dementia.

While Bird and others argue that the epigenome is predominantly under genetic control, some researchers are interested in the trace that certain environmental insults leave there. Smoking, for example, has a clear epigenetic signature. I could tell you quite accurately, based on their DNA methylation profile, if someone was a smoker or not, and probably how much they smoked and how long they had smoked for, says Mill.

James Flanagan of Imperial College London is among those who are exploiting this aspect of the epigenome to try to understand how lifestyle factors such as smoking, alcohol and obesity shape cancer risk. Indeed, cancer is the area where there is most excitement in terms of the clinical application of epigenetics. One idea, Flanagan says, is that once informed of their risk a person could make lifestyle adjustments to reduce it.

Drugs that remodel the epigenome have been used therapeutically in those already diagnosed with cancer, though they tend to have bad side-effects because their epigenetic impact is so broad. Other widely prescribed drugs that have few side-effects might turn out to work at least partly via the epigenome too. Based on the striking observation that breast cancer risk is more than halved in diabetes patients who have taken the diabetes drug metformin for a long time, Flanagans group is investigating whether this protective effect is mediated by altered epigenetic patterns.

Meanwhile, the US-based company Grail which has just been bought, controversially, by DNA sequencing giant Illumina has come up with a test for more than 50 cancers that detects altered methylation patterns in DNA circulating freely in the blood.

Based on publicly available data on its false-positive and false-negative rates, the Grail test looks very promising, says Tomasz K Wojdacz, who studies clinical epigenetics at the Pomeranian Medical University in Szczecin, Poland. But more data is needed and is being collected now in a major clinical trial in the NHS. The idea is that the test would be used to screen populations, identifying individuals at risk who would then be guided towards more classical diagnostic procedures such as tissue-specific biopsies. It could be a gamechanger in cancer, Wojdacz thinks, but it also raises ethical dilemmas, that will have to be addressed before it is rolled out. Imagine that someone got a positive result but further investigations revealed nothing, he says. You cant put that kind of psychological burden on a patient.

The jury is out on whether its possible to wind back the epigenetic clock. This question is the subject of serious inquiry, but many researchers worry that as a wave of epigenetic cosmetics hits the market, people are parting with their money on the basis of scientifically unsupported claims. Science has only scratched the surface of the epigenome, says Flanagan. The speed at which these things happen and the speed at which they might change back is not known. It might be the fate of every young science to be misunderstood. Thats still true of epidenetics, but it could about to change.

Until recently, sequencing the epigenome was a relatively slow and expensive affair. To identify all the methyl tags on the genome, for example, would require two distinct sequencing efforts and a chemical manipulation in between. In the past few years, however, it has become possible to sequence the genome and its methylation pattern simultaneously, halving the cost and doubling the speed.

Oxford Nanopore Technologies, the British company responsible for much of the tracking of the global spread of Covid-19 variants, which floated on the London Stock Exchange last week, offers such a technology. It works by pushing DNA through a nanoscale hole while current passes either side. DNA consists of four bases or letters A, C, G and T and because each one has a unique shape in the nanopore it distorts the current in a unique and measurable way. A methylated base has its own distinctive shape, meaning it can be detected as a fifth letter.

The US firm Illumina, which leads the global DNA sequencing market, offers a different technique, and chemist Shankar Balasubramanian of the University of Cambridge has said that his company, Cambridge Epigenetix, will soon announce its own epigenetic sequencing technology one that could add a sixth letter in the form of hydroxymethyl tags.

Protein modifications still have to be sequenced separately, but some people include RNA modifications in their definition of epigenetics and at least some of these technologies can detect those too meaning they have the power to generate enormous amounts of new information about how our genetic material is modified in our lifetime. Thats why Ewan Birney who co-directs the European Bioinformatics Institute in Hinxton, Cambridgeshire, and who is a consultant to Oxford Nanopore, says that epigenetic sequencing stands poised to revolutionise science: Were opening up an entirely new world.

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Epigenetics, the misunderstood science that could shed new light on ageing - The Guardian

Bears take their porridge differently, and patients respond to drug treatments differently. At FameLab, genetics researcher Ifeolutembi Fashina explained how we can learn from a database of taste tests to perfect drug doses for patients in need.

Ifeolutembi Fashina entered the world of human genetics during her undergraduate degree at Trinity College Dublin. Then, after a couple of years in the industry, reporting adverse events in clinical trials, she joined the McCoy Lab at Royal College of Surgeons in Ireland (RCSI) under funding by Science Foundation Irelands Centre for Research Training in Genomics.

In her PhD research, Fashina is exploring how changes to human microRNAs could influence multiple sclerosis. But when she entered the FameLab science communication competition earlier this year, she tapped into her earlier research interests.

It was during her final-year project at Trinity, working in the lab of one of Irelands leading geneticists, Prof Aoife McLysaght, that Fashinas interest in bioinformatics was piqued.

Bioinformatics involves the use of software to understand and interrogate large, complex biological datasets. And Fashinas three-minute presentation on how drug and enzyme databases can be used to determine accurate medication doses for patients scored her third place in the recent FameLab Ireland final.

She said, I wanted to show that it is possible to use genetic information to solve a healthcare problem.

Now that we have done more genetic studies in humans, we can see how small changes to a persons genes can affect the way they break down pain medicine IFEOLUTEMBI FASHINA

I would say that it was more of a series of realisations than a spark. In secondary school, I enjoyed a broad range of subjects, but my favourites were maths, agricultural science, economics and biology. Since most of these were STEM leaning, it was expected that I would study medicine in university (in the typical Nigerian way). That was not what I wanted.

I became very invested in crime shows during this period, and read Forensic Science by Andrew and Julie Jackson. The use of genetic information to solve crime really captured my interest, and when I joined the human genetics programme in Trinity, the researchers in the department really opened my eyes to how many health problems we could address by understanding how genes work.

I noticed that when talking to my family and non-scientist friends, there were some ideas that I had encountered several times, but they had not come across at all. These would have been important updates in the scientific community, especially about the genetic basis of some common diseases. So I thought it would be interesting to try to talk about genes in a simple way and to hopefully give people some context when they are reading or hearing about new discoveries.

To prepare, I noted three points I wanted to make, and recorded myself talking around them. From those, I wrote multiple drafts of my talk. I had two friends and my mum (a non-scientist) listen to the talk and give feedback. Two of my lab-mates, Conor Duffy and Remsha Afzal, are FameLab alumni, so their support and that of my PhD supervisors and our lab members helped my journey too.

Ive loved learning from the other participants, especially the way they tell their stories so differently but also effectively. I also appreciated getting feedback from the judges in the regional heats, especially Phil Smyth, and guidance from Jonathan McCrea and Malcolm Love in the masterclass.

Clinicians and scientists have known for a while now that drugs are not one-size-fits-all. On the other hand, many patients experience severe pain, so they need adequate pain relief.

Now that we have done more genetic studies in humans, we can see how small changes to a persons genes can affect the way they break down pain medicine. That means that we can use those genetic changes to predict which dose or painkillers will work for them best.

Explaining concepts without introducing too many technical terms is challenging, so I try to use analogies and to focus on one concept at a time.

I think the process of updating ideas that the public has already accepted might be a bit tricky. I would like for people to think of scientific facts as being the consensus as we understand so far, pending better, well-replicated evidence. So that means that when we have better evidence, the story could change, but it does not mean that the first story was wrong. Its just more like a building block.

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Like Goldilocks, genetics research can find the dose that's just right - Siliconrepublic.com

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Genetics and the link to breast cancer | Mobile County Alabama News | fox10tv.com - FOX10 News

The company is leveraging success with its COVID-19 tests to position itself better for a post-pandemic world. Key Points

Fulgent Genetics' (NASDAQ:FLGT) sales soared thanks to its COVID-19 tests. Its stock more than quadrupled in 2020 and is up over 50% so far this year. In this Motley Fool Live video recorded on Sept. 29, 2021, Motley Fool contributors Keith Speights and Brian Orelli discuss what's going on now with Fulgent.

Keith Speights: Your thoughts on Fulgent Genetics, ticker is FLGT?

Brian Orelli: The company is still developing genetic tests, which was what they were doing before the pandemic. They're still doing COVID-19 testing, which is what they pivoted or added during the pandemic. Then they are using all that cash that they're getting from the COVID-19 to expand fairly quickly.

They bought a company that does more other types of tests for cancers, looking at imaging the tumors and that thing and looking at the chromosomes. I think that they are using that to expand their offerings, so now that they will be able to do genetic testing on the tumors, but also offer other services. That should make them a one-stop-shop for tumors.

They also did a deal with another company that has a predictive test, I believe, for cancer. They're partnering with that company. The other one was an acquisition where they just bought the whole testing facility to expand their offerings in cancer.

This article represents the opinion of the writer, who may disagree with the official recommendation position of a Motley Fool premium advisory service. Were motley! Questioning an investing thesis -- even one of our own -- helps us all think critically about investing and make decisions that help us become smarter, happier, and richer.

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What's Going on With Fulgent Genetics? - The Motley Fool

USPOULTRY and the USPOULTRY Foundation announce the completion of a funded research project at the University of Maryland in College Park, Maryland, in which researchers identified the contribution of broiler genetics on gut health and immune response when challenged with Salmonella Typhimurium.

The research was made possible in part by an endowing Foundation gift from Ingram Farms and is part of the Associations comprehensive research program encompassing all phases of poultry and egg production and processing. A summary of the completed project is as follows.

(Dr Shawna Weimer, Department of Animal and Avian Sciences, University of Maryland, College Park, Maryland)

Dr Shawna Weimer and colleagues at the University of Maryland recently completed a research project that evaluated the differences in immune response, gut morphology and microbiome, and behavior of fast- and slow-growing broiler chickens challenged with Salmonella typhimurium.

The results showed that Salmonella did induce a small variety of responses, including impaired intestinal morphology in fast-growing birds at 24 days and elevated IgA concentrations at 21 days in the slow-growing birds. The fast-growing birds were heavier, had greater jejunum gut integrity, and greater concentrations of immunoglobulins IgA and IgG in blood plasma by 24 days.

Slow-growing birds had greater IgG concentrations at 7 days and their gut integrity was more resilient to challenge by 24 days. Behaviorally, fast-growing broilers were less exploratory, social and aggressive than slow growing. Birds from both breeds and challenge treatments sat more and stood less on days 16 and 20 after challenge, which the researchers hypothesize could have been due to the stress of subjection to oral gavage.

The results of this study indicate that meaningful genotypic and phenotypic differences exist between fast- and slow-growing broiler body weight, immune response, gut morphology and microbial communities, and behavior when challenged with Salmonella typhimurium. Delineating the differences in basal and Salmonella-challenged phenotypes of broilers with divergent growth rates provides useful information for genetic, nutritional and management decisions.

Overall findings showed that breed had a much stronger effect than Salmonella challenge, indicating that meaningful genotypic and phenotypic differences exist between fast- and slow-growing broiler body weight, immune response, gut morphology and microbial communities, and behavior when challenged with Salmonella typhimurium.

The research summary can be found on the USPOULTRY website.

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Link between broiler genetics, gut health and immune response becomes clearer in University of Maryland study - The Poultry Site

Every two weeks, members of the Yale Genetics Diversity Advisory Committee (DAC) come together to discuss ways to address equity and inclusion across all underrepresented memberships within the department. These discussions are centered around four major areas: i) understanding the challenges that members of our community from underrepresented backgrounds face, ii) scrutinizing and formalizing a more equitable approach to hiring, iii) educating members of the community at all career stages and job functions in how to eliminate current exclusionary practices, and iv) investing in the support and retention of underrepresented minorities within the department. The committee operates within a network of Yale-wide diversity, equity, and inclusion (DEI) efforts led by Deputy Dean and Chief Diversity Officer Dr. Darin Latimore together with Associate Dean of Diversity and Inclusion & Associate Chief Diversity Officer Rochelle Smith, both from the Yale School of Medicines Office of Diversity, Equity, and Inclusion.

DAC was formed in October 2020 and is led by the Vice Chair of Diversity in the department, Dr. Valentina Greco. The overarching goal of DAC is to provide a lens through which to scrutinize and improve all departmental practices to embrace, enrich, and support a greater diversity within the departmental membership. The committee members partner closely with departmental members and leadership to achieve this. DAC members also act as representatives for other community members at their professional level undergraduate, post-graduate, graduate students, post-doc, administrative staff and lab professionals, clinical staff, and junior and senior faculty updating their peers on DAC efforts and bringing forth the concerns of their circles to the committee. Committee members communicate regularly with each other through a Slack platform, educating themselves and supporting each other in this critical work. The committee members are individuals with diverse backgrounds and different lived experiences who must be brave, vulnerable, and open with each other as they discuss the resistance within and outside the community to implement cultural change.

One of the areas where DAC is currently focusing its efforts on is the departments hiring practices, closely collaborating with faculty members and departmental leadership to develop an approach that both attracts and enriches for diverse memberships. To this end, DAC has recently provided extensive review and feedback of departmental guidelines for the recruitment of new junior faculty. These guidelines span from the initial wording of the advertisement to procedures detailing best practices for scoring applications, conducting interviews, and advancing candidates at each stage of review. Once approved, the guidelines will help to ensure that diversity is embedded in every faculty search going forward as a core value of the department, and that proactive steps to promote diversity in faculty hiring are consistently taken, regardless of who is directing the search.

Just as important as diversifying the candidate pool is ensuring that the department can support and retain its diverse faculty members. On its own, recruiting diverse candidates will not fix problems of equity and inclusion in the department this would only perpetuate such problems by creating a false sense that the culture has become more inclusive and supportive simply through diverse recruitment efforts, instead of addressing the underlying barriers that have traditionally excluded diverse members in the first place. To provide an authentically supportive environment for vulnerable memberships within the department, DAC is helping to implement an infrastructure for everyday processes, ranging from mentoring to promotion criteria, that continually scrutinizes and improves itself to be equitable for everyone.

DAC meetings create intentional spaces for scrutiny and to brainstorm solutions. However, it is also important to note that efforts to address inequity have been underway in the department even before the formation of DAC. In 2019, Dr. Caroline Hendry, Scientific Director and Advisor to the Chair of Genetics, spearheaded the Program to Support and Retain Women Faculty in Genetics, partnering with long-time advocate of gender equity Dr. Valentina Greco, as well as senior women faculty in the department Dr. Lynn Cooley, Dr. Valerie Reinke, and Dr. Hui Zhang. The program was designed in consultation with Dr. David Berg, Clinical Professor of Psychiatry and an expert in organizational behavior and group and intergroup relations. The program takes a holistic approach to both support the professional advancement of women faculty in Genetics and to begin to break down the socio-cultural barriers that have impeded their advancement thus far. The Program to Support and Retain Women Faculty in Genetics has equipped me with tools to develop my managerial skills on a more personalized basis, says Dr. Kaelyn Sumigray, Assistant Professor of Genetics. She shares that the program provided a much-needed support system for developing my research program at a critical time in my career. The program spans four key areas: i) creating opportunities for women to become leaders, ii) scrutinizing and reassigning the distribution of burden and invisible labor in the department, iii) deconstructing gender stereotypes that limit career progression, and iv) establishing best practices for life-work integration. Importantly, the program includes men in the department insofar as they must be willing to take an active role in recognizing and addressing their privilege and role in perpetuating the structural, cultural and organizational barriers that have so far restricted womens careers in science from advancing on par with their male colleagues. Many aspects of the program can and are applied to other groups that are currently underrepresented in the department not just women in order to support and retain all vulnerable memberships.

More recently, the committee has expanded its efforts in training and educating the department on topics primarily at the intersection of race and genetics and issues of discrimination. The Equity Journal Club (EJC) was established by the departments trainees and staff in response to the social movement that came from the murder of George Floyd. It is another example of a diversity initiative that existed prior to DAC, and DAC is now working to expand the initiative and incorporate it into the more routine Research in Progress forum in the department as part of the departments ongoing educational mission. It is a sign of our commitment to learn and improve as a collective group," says Maria Benitez, a Genetics student and DAC representative. The DAC and EJC are in the midst of planning speaker events open to the Yale community to expand the conversation around the intersection of racism, genetic research, and health equity. DAC members also have a vision of putting together a library, compiling literature on anti-racism and systemic discrimination that anyone can access to educate themselves.

Dismantling structural bias and discrimination against people of diverse racial and ethnic groups, persons with disabilities, the LGBTQ+ community, people from low socioeconomic backgrounds, and other vulnerable memberships is a long-term project. It cannot be solved by one individual leader, but requires peers to unite as followers of a movement that collectively desires and is willing to make the effort for change. Dr. Greco emphasizes the need for each member in the Yale Genetics community to bring a dedicated and serious commitment to change ourselves in order to make space for others. The exceptionalism and individualism that academia is built on is antithetic to the notion that talent is widespread. Furthermore, consciously or unconsciously, we perpetuate with our actions the false belief that talent can only be found in the few memberships consistent with the appearances of those who currently hold the most power and privilege, Greco continues. DAC believes that this ideological disconnect is the biggest resistance that the department faces in moving forward with DEI initiatives. Members of the department must realize that talent is present in groups that have historically and continue to be only tolerated, suppressed, or entirely excluded at various levels on the academic ladder.

Yale Genetics DAC and members of DEI committees across Yale continue to reflect on privilege and take action to make the department and the institution a more equitable place. Though there is still so much to be done, with the ongoing activism of DAC members and the collaboration of the entire department, Yale Genetics is determined to build a more inclusive environment for all.

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Collective Efforts to Increase Diversity, Equity, and Inclusion in the Genetics Department Make Steady Progress - Yale School of Medicine

NEW YORK A suite of new studies has examined how one cell develops into all the tissues of the human body by tracing and investigating the mutations they acquire over time.

As cells divide, they acquire mutations that are then passed on to their daughter cells. The resulting patterns of mutations can be used to trace back a cell's family tree, possibly all the way to the first cell. In four new studies appearing Wednesday in Nature, teams of researchers from across the world used this approach to study the earliest stages of human development as well as the later accumulation of somatic mutations, including ones linked to cancer.

"Exploring the human body via the mutations cells acquire as we age is as close as we can get to studying human biology in vivo," Luiza Moore, a researcher at the Wellcome Sanger Institute and first author of one of the studies, said in a statement. "Our life history can be found in the history of our cells, but these studies show that this history is more complex than we might have assumed."

Tracing these mutations back in time revealed differences in mutation rates very early in embryonic development. Researchers led by the Sanger Institute's Michael Stratton uncovered a pattern of mutations that indicated a high initial mutation rate that then fell in a study that combined laser capture microdissections with whole-genome sequencing of samples from three individuals. A team led by the Korea Advanced Institute of Science and Technology's Young Seok Ju similarly found a high mutational rate during the early stages of development that then declined, using a capture-recapture approach.

The Stratton-led team estimated that the first two cell divisions had mutation rates of 2.4 per cell per generation, which then fell to 0.7 per cell per generation. This dip, they said, is likely due to the activation of the zygotic genome that increases the ability to repair DNA.

These early cells also contributed unequally to the development of subsequent lineages, though the degree of asymmetry varied from person to person. Ju and his colleagues reported, for instance, that for one individual in their analysis, 112 early lineages split at a ratio of 6.5:1, rather than the expected 1:1.

Stratton and his colleagues, meanwhile, reported that one individual in their study had a 69:31 contribution of the initial daughter cells to subsequent lineages, while another had a 93:7 ratio based on bulk brain samples, but an 81:19 ratio based on colon samples.

This, they said, indicates that the lineage commitment of cells is not fixed. Ju and his colleagues likewise said their finding suggested a stochasticity of clonal segregation in humans, unlike the deterministic embryogenesis observed in C. elegans.

These analyses also shed light on the development of somatic mutations later in life. KAIST's Ju and his colleagues, for instance, found most mutations are specific to certain clones, while in a separate study, the Sanger's Moore and her colleagues, who examined the mutational landscape of 29 cell types from three individuals through sequencing, found mutationrates varied by cell type and were very low in spermatogonia.

Ju and his colleagues also reported that normal tissues harbored known mutational signatures, including UV-mediated DNA damage and endogenous clock-like mutagenesis. Similarly, Moore and her colleagues noted known mutational signatures within normal tissues. They found, for instance, the aging-related SBS1 and SBS5 mutational signatures to be the most common signatures across all cell types, while other signatures were more prominent in certain cell types but not others. The SBS88 signature, which is due to a strain of E. coli, for example, was present among colorectal and appendiceal crypts.

Chen Wu, an investigator at the Chinese Academy of Medical Sciences, and her colleagues also found the aging-related SBS1 and SBS5 mutational signatures to be common among normal tissues, based on their sequencing analysis of microbiopsies from five individuals. Other tissues, like the liver and lung, also harbored other mutational signature like SBS4, which is associated with tobacco smoking.

Some of the mutations present in normal somatic tissues are typically associated with cancer, Wu and her colleagues added. They found mutations in 32 cancer driver genes were widespread among their normal tissue samples, though varied by organ. For instance, driver mutations were present in 6.5 percent of pancreas parenchyma samples and in 73.8 percent of esophageal samples.

Additionally, many normal tissue samples harbored as many as three cancer driver mutations. This, Harvard Medical School's Kamila Naxerova noted in a related commentary in Nature, begins to blur the line between what is normal and what is cancer. "Indeed, if cells with three driver mutations can easily be found in a small tissue sample, cells with four or five drivers probably exist in that tissue as well without necessarily giving rise to cancer," she wrote. "These new insights invite us to reconsider how we genetically define cancer."

Overall, she added that "the four studies provide an impressive demonstration of the power of modern genetics to decode the cellular dynamics that unfold in our bodies over time."

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Genetic Analyses Trace How Mutations Accumulate in Cells of the Human Body Over Time - GenomeWeb

A bat in flight.

Bats have developed a pretty bad rap sheet in the last few years. First, pop culture painted these mammals as a form of the blood-sucking Dracula, and then they were villainised for allegedly triggering a pandemic. Indeed, these poor creatures can't seem to catch a break! Aside from being adorable, bats have several other redeeming qualities like being the only mammals capable of flying and finding food even in complete darkness.

Of late, experts in genetics have uncovered a few startling facts about these Chiropterans, which could imply that they may hold the secret to healthy ageing. With the COVID-19 pandemic turning the spotlight on bats, their unique ability to stay alive against unmatched odds has also come under scrutiny.

The relationship between the size of a mammal, its metabolism, and lifespan is relatively straightforward. The larger the mammal, the slower its metabolism is, and this means a longer lifespan. While we humans ourselves are an exception to this rule, these flying mammals also deviate from this trend.

Some bats are known to live for 40 yearsthat's eight times longer than the lifespan of other animals their size! This unusually long lifespan of bats has always aroused the curiosity of scientistsit prompted them to ask the question, what was it that made these bats live longer?

The gene expression pattern in bats is very unique and has been associated with DNA repair, autophagy, immunity and tumour suppression, ensuring an extended health span for bats. Now, scientists are wondering if we could replicate a few such attributes on humans as well!

There's a cap-like structure called the telomere present at the end of each chromosomea microscopic threadlike part of the cell that carries part or all of the genetic material. This unique structure protects your chromosomes from damage. Every time your cells replicate, the chromosome loses just a little bit of the telomere. As time passes, this telomere gets very short, and either rides the wave of ageing or causes the cell to self-destruct. To put it succinctly, the shortening of your telomeres is why you age.

While this seems inevitable, studies conducted in the last few years revealed that the telomeres do not shorten in long-lived species of batslike the Myotis genus. This means that these species can protect their DNA for an unusually long-time in their lifespan.

A bat pup.

It's common knowledge that in humans, the body's ability to heal and repair any damage decreases considerably as we age. But researchers studied the genome of young, middle-aged, and old bats and found that their ability to repair DNA and damage caused by age increased as they grew older.

Another quality that contributes to their longevity is their ability to control their immune responses. With an over-excited immune response, humans tend to succumb to infections like COVID-19 quicker. In COVID-19 patients with regulated immune responses, the risk of ending up on the ventilator is much lower, reveals research.

Similarly, a controlled immune response could be why bats are able to carry numerous deadly pathogens like the coronavirus without succumbing to them easily.

Humans and bats have many similar genes but with a tweak here and a nip there. So, if we could someday discover what factors elicit these controlled immune responses and telomere shortening avoidance in bats and replicate it in humans, it would be a massive leap towards the utopian dream of a healthy, long life!

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The Bat Elixir: Geneticists Suspect that the Flying Mammal Holds the Key to Extended Healthy Life | The Weather Channel - Articles from The Weather...

When Joseph Dalton Hooker, director of the Kew Royal Botanical Gardens in London between 1865 and 1885, first cast his gaze on an example of Welwitschia he could not contain himself: It is without question the most wonderful plant ever brought to this country, and one of the ugliest. This species, Welwitschia mirabilis, was first formally described in 1863 and has been the subject of debate ever since it was first discovered. It has been established that it can survive for thousands of years in the harshest environments, making it the longest-living plant on the planet. But a recent genetic analysis published in Nature Communications has revealed new data about this curious plant species. Welwitschias duplicated genome means that some of its genes can dedicate themselves to tasks that are not part of their original functions. Furthermore, this species can activate certain proteins to protect itself from the extreme conditions in which it lives and it grows slowly but continuously throughout its entire life.

Welwitschia is found in Namibias northwest and southeastern Angola, an area dominated by the Kaokoveld Desert. Despite being geographically near to the coast, this region is arid and annual rainfall is less than five cubic centimeters. The plants appearance is also distinctive, consisting of two foliage leaves that can grow by 10 to 13 centimeters each year. As they grow, the tips of the leaves dry out and curl together, which sometimes lends the plant an appearance similar to an octopus.

Genome analysis of Welwitschia has shown that all of its genes are duplicated, what experts describe as genetic redundancy. Andrew Leitch, a researcher at the Queen Mary University of London and one of the authors of the study, explains how this duplicity, over the course of millions of years, has altered the functioning of these genes: The duplicated copies can take on new functions and do new things that would be impossible if there was only one version of the gene. These adaptations have driven the evolution of the plants. For example, the researchers believe that the leaves are capable of absorbing some of the humidity from clouds of mist that form in the plants natural habitat when dawn breaks.

Welwitschias genetic duplication began around 86 million years ago and was prompted by the stress placed on the plants by being constantly exposed to some of the harshest environmental conditions on the planet (high temperatures, ultraviolet radiation, salinity and so forth). In the face of this constant assault, Welwitschia always maintains a variety of proteins overactivated that allow the plant to keep these environmental stress factors at bay. Leitch explains it with a culinary example: When you put an egg in boiling water, the proteins in the egg are denatured and the white of the egg hardens. This denaturalization is a problem for the plants and animals that live in conditions of extreme heat and Welwitschia activates certain genes to prevent this from happening.

Identifying genes that allow for survival in hostile conditions will be useful when we are looking to grow crops in ever more marginal areas of the planet

Furthermore, unlike other plants, Welwitschias growth does not occur at the tips of the leaves but at the base. This area of the plant is heavily protected by two lips consisting of a woody fiber that cover the basal meristem, the part of the plant that supplies new cells. This type of bulb is formed of a practically embryonic tissue, still poorly defined, that gradually transforms into leaf tissue at a very slow pace. While this bulb lives, the plant will never stop growing. As such, the name given to it in Afrikaans is tweeblaarkanniedood, which literally translates astwo leaves that cannot die. The plants can live to such an age that the researchers had to use carbon-dating technology usually reserved for fossils to determine how old their subjects were. The results confirmed that some individuals were more than 1,500 years old.

Leitch believes that this discovery could prove to be key in the medium- to long-term for the survival of the human race. Identifying genes that allow for survival in hostile conditions will be useful when we are looking to grow crops in ever more marginal areas of the planet, something that we will have to do to be able to feed the nine billion people that we will be within the next 50 years with a high-level diet, as well as finding space for bio-combustibles. And all of that has to be achieved in a context of climate change and alterations in rainfall and temperature.

Alfonso Blzquez, a professor and researcher at the Autonomous University of Madrid who did not take part in the study, harbors doubt over the viability of this potential application. Overexpressing one or two genes in commercial crops is unlikely to achieve the same effect, because this plant has a battery of protective genes activated at the same time, but they may obtain some kind of greater resistance to heat or a lack of humidity. This could be an intermediate application that should be investigated.

English version by Rob Train.

Read more:
Welwitschia: genetics unveil the secrets of the immortal plant - EL PAS in English