Category Archives: Human Genetics

Newswise The finding that some genes are active from the get-go challenges the textbook view that genes don't become active in human embryos until they are made up of four-to-eight cells, two or three days after fertilisation.

The newly discovered activity begins at the one-cell stage far sooner than previously thought promising to change the way we think about our developmental origins.

The research, published today in Cell Stem Cell, was co-led byProfessor Tony Perryat the University of Bath, Dr Giles Yeo at the University of Cambridge and Dr Matthew VerMilyea at Ovation Fertility, US.

Using a method called RNA-sequencing, the team applied precision analysis to individual human eggs and one-cell embryos to make a detailed inventory of tell-tale products of gene activity, called RNA transcripts. It revealed that hundreds of genes awaken in human one-cell embryos. Because the gene activity starts small, previous techniques had not been sensitive enough to detect it. But state-of-the art RNA-sequencing used in this study was able to reveal even small changes.

"This is the first good look at the beginning of a biological process that we all go through the transit through the one-cell embryo stage," said Professor Perry, from the Department of Biology and Biochemistry at Bath. "Without genome awakening, development fails, so it's a fundamental step."

The team found that many genes activated in one-cell embryos remain switched on until the four-to-eight cell stage, at which point they are switched off.

It looks as if there is a sort of genetic shift-work in early embryos: the first shift starts soon after fertilisation, in one-cell embryos, and a second shift takes over at the eight-cell stage, said Professor Perry.

At the moment of human fertilisation, sperm and egg genomes the collection of all of their genes are inactive: the sperm and egg rely on transcripts produced when they were being formed for instructions that regulate their characteristics.

Transcripts provide essential instructions in all cells, and embryo cells are no exception. This means that it is essential for parental (sperm and egg) genomes to awaken in the new embryo. But when and how does this happen?

Understanding the process of genome awakening is important: it is a key piece of the jigsaw of development that promises a better understanding of disease, inheritance and infertility. The scientists found some activated genes that might be expected to play roles in early embryos, but the roles of others were unknown and could point to embryonic events that we don't yet understand.

The team's findings also shine a light on how the genes are activated. "Although the trigger for activation is thought to come from the egg, it's not known how; now we know which genes are involved, we can locate their addresses and use molecular techniques to find out," said Professor Perry.

Remarkably, candidates that might trigger gene activation include factors usually associated with cancer, such as some well-known oncogenes. This led the researchers to speculate that the natural, healthy role of factors that are known to misbehave in cancer, is to awaken genes in one-cell embryos. If this proves to be correct, the teams findings could illuminate events that initiate cancer, providing new diagnostic and preventive opportunities.

The findings also have clinical implications for the inheritance of acquired traits, such as obesity: parents who gain weight seem to pass the trait to their kids. It is not known how such acquired traits are transmitted, but altering gene activation after fertilisation is a possible mechanism.

As Dr Yeo from the Medical Research Council Metabolic Diseases Unit at Cambridge suggests, "If true, we should be able to see this altered gene activation signature at the one cell stage."

The team also looked at unhealthy one-cell embryos that do not go on to develop, and found that many of their genes fail to activate. Abnormal embryos have been used to evaluate methods of human heritable genome editing, but the new findings suggest they may be inappropriate as a reliable test system.

ENDS

University of Bath

The University of Bath is one of the UK's leading universities both in terms of research and our reputation for excellence in teaching, learning and graduate prospects.

The University is rated Gold in the Teaching Excellence Framework (TEF), the Governments assessment of teaching quality in universities, meaning its teaching is of the highest quality in the UK.

In the Research Excellence Framework (REF) 2014 research assessment 87 per cent of our research was defined as world-leading or internationally excellent. From developing fuel-efficient cars of the future, to identifying infectious diseases more quickly, or working to improve the lives of female farmers in West Africa, research from Bath is making a difference around the world. Find out more:http://www.bath.ac.uk/research/

Well established as a nurturing environment for enterprising minds, Bath is ranked highly in all national league tables. We are ranked 8th in the UK by The Guardian University Guide 2022, and 9th in The Times & Sunday Times Good University Guide 2022 and 10thin the Complete University Guide 2022. Our sports offering was rated as being in the worlds top 10 in the QS World University Rankings by Subject in 2021.

About the MRC Metabolic Diseases Unit

The MRC Metabolic Diseases Unit is based at the Wellcome-MRC Institute of Metabolic Science. It supports research to improve understanding of the basic mechanisms responsible for obesity and related metabolic diseases. This knowledge underpins the development of interventions to prevent and treat these conditions.

About the University of Cambridge

The University of Cambridge is one of the worlds top ten leading universities, with a rich history of radical thinking dating back to 1209. Its mission is to contribute to society through the pursuit of education, learning and research at the highest international levels of excellence.

The University comprises 31 autonomous Colleges and 150 departments, faculties and institutions. Its 24,450 student body includes more than 9,000 international students from 147 countries. In 2020, 70.6% of its new undergraduate students were from state schools and 21.6% from economically disadvantaged areas.

Cambridge research spans almost every discipline, from science, technology, engineering and medicine through to the arts, humanities and social sciences, with multi-disciplinary teams working to address major global challenges. Its researchers provide academic leadership, develop strategic partnerships and collaborate with colleagues worldwide.

The University sits at the heart of the Cambridge cluster, in which more than 5,300 knowledge-intensive firms employ more than 67,000 people and generate 18 billion in turnover. Cambridge has the highest number of patent applications per 100,000 residents in the UK. http://www.cam.ac.uk

About Ovation Fertility

OvationFertility is a national network of reproductive endocrinologists and scientific thought leaders focused on reducing the cost of having a family through more efficient and effective fertility care. Ovations IVF and genetics laboratories, along with affiliated physician practices, work collaboratively to raise the bar for IVF treatment, with state-of-the-art, evidence-based fertility services that give hopeful parents the best chance for a successful pregnancy. Physicians partner with Ovation to offer their patients advanced preconception carrier screening; preimplantation genetic testing; donor egg and surrogacy services; and secure storage for their frozen eggs, embryos and sperm. Ovation also helps IVF labs across America improve their quality and performance with expert off-site lab direction and consultation. Learn more about Ovations vision of a world without infertility at: http://www.OvationFertility.com.

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Genes are switched on in the human embryo from the get-go - Newswise

NEW YORK Researchers have identified in a multi-ancestry cohort almost three dozen genes associated with blood lipid levels that are risk factors for atherosclerotic cardiovascular diseases.

While previous genome-wide association studies have linked more than 400 genetic loci to blood lipid levels, these loci explain between 9 percent and 12 percent of the phenotypic variance found among lipid traits.

In a new study, an international team of researchers has conducted gene-based association testing of blood lipid levels with rare and likely damaging gene variants using a dataset of more than 170,000 individuals of multiple ancestries. As they reported in the American Journal of Human Genetics on Monday, the researchers identified 35 genes linked to circulating lipid levels, including genes not previously associated with lipid levels, including ones found among individuals of differing ancestries.

"I would expect that genes that are associated across multiple ancestries to be more robust findings compared to ones we only see in one ancestry," senior author Gina Peloso from the Boston University School of Public Health said in an email. "We might not see the same variants in a gene associated in multiple ancestries, but finding genetic variants associated in different ancestries helps us cross validate the associations."

These genes were further enriched for the targets of cholesterol-lowering drugs and indicated that, contrary to other studies, the gene located closest to the GWAS index SNP may often be the functional gene.

For their analysis, the researchers combined data from four sources that amassed either exome or genome sequencing data alongside blood lipid level information and, in all, their dataset included more than 170,000 individuals including 97,493 Europeans, 30,025 South Asians, 16,507 Africans, 16,440 Hispanic individuals or Latinos, 10,420 East Asians, and 1,182 Samoans.

At the same time, the researchers focused on six lipid phenotypes for their analysis, including total cholesterol, LDL-Cl, HDL-C, non-HDL-C, triglycerides, and TG:HDL.

In a single-variant association analysis, the researchers uncovered hundreds of rare coding variants associated with those different lipid traits. But by then conducting a gene-based analysis of transcript-altering variants, they homed in on 35 genes that reached exome-wide significance. Most of these genes, the researchers noted, were associated with more than one lipid trait. Ten of them had not previously been associated with blood lipid phenotypes.

Most, 27, of these genes are located within 200 kilobases of GWAS-indexed SNPs for blood lipid traits, the researchers found. They further investigated whether these genes were linked to the corresponding lipid measurement, finding that they were, suggesting that the closest gene to a noncoding GWAS signal is most likely the causal one and should be prioritized for follow-up. They noted, though, that some previous studies have instead found the closest genes to a GWAS signal do not show an association with the phenotype under study.

"This could be due to the type of variation we tested rare protein-altering variation compared to looking at variation that might influence gene regulatory mechanisms," Peloso noted.

The genes the researchers identified through their gene-based analysis were broadly consistent across ancestry groups. For instance, three of the 17 genes associated with HDL-C showed that association in a least two ancestry groups at exome-wide significance, while five of the 14 genes linked to total cholesterol did, and four of the 10 genes linked to non-HDL-C did.

They further reported that these genes were enriched for LDL-C drug targets. "While the genes that we identified might represent drug targets, further work will be necessary to determine whether those genes are druggable and influence clinical events," she added.

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Analysis of Multi-Ancestry Cohort Uncovers Dozens of Genes Linked to Blood Lipid Levels - GenomeWeb

Wilmot Cancer Institute researchers are a step closer to understanding the complex gene interactions that cause a cell to become malignant. In a new Cell Reports study published today, the group used network modeling to hone in on a set of such interactions that are critical to malignancy, and likely to be fertile ground for broad cancer therapies.

Discrete genetic mutations that can be targeted by drugs have only been identified for a small fraction of cancer types. But those mutations rely on a downstream network of non-mutated genes in order to cause cancer. Those downstream genes and their intricate interactions may be common across many cancers and could offer a giant leap forward in cancer therapy.

One of the lead authors of the study, Hartmut Hucky Land, Ph.D., thedeputy director of the Wilmot Cancer Institute and the Robert and Dorothy Markin Professor of Biomedical Genetics at the University of Rochester Medical Center,has worked to identify common core features of cancers for over 10 years. His goal is to find cancers shared vulnerabilities and exploit them.

Targeting non-mutated proteins that are essential to making cells cancerous is a broader approach that could be used in multiple cancers, said Land, but its hard to find these non-mutated, essential genes.

That is why Land turned to Matthew McCall, Ph.D., MHS, a Wilmot Cancer Institute investigator who is an associate professor of Biostatistics and Computational Biology at URMC, for collaboration. McCall, who is the other lead author of the study, developed a new network modeling method, called TopNet, that the group paired with genetic experiments in cells and mice to pinpoint functionally relevant gene networks.

Lands group previously identified a very diverse set of non-mutated genes that are crucial to cancer. In this study, the group wanted to see how those genes interact starting with a subset of 20 genes. Increasing or decreasing the expression of one gene in cultured cells would have numerous effects on the expression levels of the other genes in the set.

There were so many interactions, you could waste a lot of time, energy and money testing interactions that might not be useful, McCall said. To hone in on the interactions that are more likely to be useful, we used network modeling, and compared our model networks back to the lab findings, McCall said.For context, the number of possible gene network models considered by TopNet was many times greater than the estimated number of atoms in the universe. After weeding out models that didnt closely fit the observed data and further focusing in on gene interactions that appeared in at least 80 percent of the models, the team was left with a manageable set of 24 high-confidence gene interactions. Subsequent experiments demonstrated that these interactions often play an important role in malignancy.

Dr. McCalls elegant and mind-boggling methodology is essentially helping us disentangle a hairball of genetic networks, said Land. These networks are usually very messy and its nearly impossible to extract useful information from them. But Dr. McCall has found a way to cut through this Gordian knot.

The group has already tested a sampling of the genetic interactions revealed by TopNet, and confirmed via experiments in cells and mice that the interactions are functionally linked. Next, the group intends to test the limits of TopNet, with the intent to use this method to find potential cancer therapies that are broadly effective.

This work was completed as part of a $6.3M National Cancer Institute Outstanding Investigator Award granted to Land in 2015 and a K99/R00 grant from the National Human Genome Research Institute to McCall. Helene McMurray, Ph.D., assistant professor of Biomedical Genetics and Pathology and Laboratory Medicine at URMC was the first author of the study.

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Honing in on Shared Network of Cancer Genes - URMC

We used to think that European wine grapes were cultivated locally, independently of grape domestication in western Asia, but grape genetics suggests otherwise

By Carissa Wong

Red grapes ready to be harvested in a vineyard

alika/Shutterstock

Grapes used to make common European wines may have originated from grapevines that were first domesticated in the South Caucasus region of western Asia. As these domesticated grapes dispersed westwards during the Greek and Roman times, they interbred with local European wild populations, which helped the wine grapes adapt to different European climates.

The origins of grapes (Vitis vinifera) that are used in Europe and elsewhere to produce wines such as Merlot, Chardonnay and Pinot Noir have long been debated.

It has been proposed that European wine grapes arose from the cultivation of wild European populations (V. viniferasubspecies sylvestris), independently of the original domestication of grapes in western Asia around 7000 years ago.

But a genetic analysis carried out by Gabriele Di Gaspero at the Institute of Applied Genomics in Udine, Italy, and his colleagues suggests that European wine grapes actually originated from domesticated grapes (V. vinifera subspecies sativa) that were initially grown for consumption as fresh fruit in western Asia.

The team sequenced the genomes of 204 wild and cultivated grape varieties to cover the range of genetic diversity in cultivated grapes and compared how similar their genetic sequences were to one another.

This revealed that as western Asian table grapes spread westwards across the Mediterranean and further inland into Europe, they interbred with wild European grape populations that grew nearby.

The wild plants grew close to vineyards and interbred this was unintentional. But the results of the breeding created adaptive traits that were likely selected by humans intentionally, says Di Gaspero. By bringing together this genetic evidence and existing historical evidence, the introductions in southern Europe and inland likely occurred in Greek and Roman times, although we dont know more specific dates.

By modelling how the ancestry of the grapes in different regions of Europe related to aspects of the local climate such as temperature and precipitation, the team discovered that European wild grapes probably contributed traits that enabled the ancestral grape vines to adapt to different regions as they moved westwards from Asia.

The team also found evidence of the effect that domestication had on grape genetics.

In wild grape varieties, a larger seed makes a larger berry because grape seeds produce a growth hormone called ethylene. But for human consumption, a larger berry-to-seed ratio is desirable. The team found that an enzyme not found in the berries of wild varieties was present in the berries of domesticated varieties. In other plants, the enzyme is known to help berries grow in response to ethylene, which suggests it does the same in grapes.

Understanding which genes encode favourable traits in grapes can allow us grow better grape crops, says Di Gaspero.

Journal reference: Nature Communications, DOI: 10.1038/s41467-021-27487-y

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European wine grapes have their genetic roots in western Asia - New Scientist

The devastating wildfires that ripped through California this year and last consumed nearly a fifth of the worlds giant sequoias, the largest trees on Earth by volume. According to official estimates, between 13 and 19 percent of the 75,000 sequoias over 4 feet in diameter were lost in just two years. While sequoias evolved with wildfire and need it to open their seed cones and to clear the forest floor so the seeds can germinate, the fires over the last two yearsexacerbated by climate change-driven droughtwere simply too hot.

Joanna Nelson, the director of science and conservation planning for the organization Save the Redwoods League, says this tree loss year after year is not sustainable for these ancient trees, which can live to be 3,000 years and older.

While they havent been hit as hard by high-intensity wildfiresyetmore than half of coast redwood forests are experiencing drought conditions that the US Drought Monitor labels extreme or exceptional. These trees rely on fog for up to 40 percent of their water each year, but summertime fog hours have declined by a third over a century.

The situation is even more dire for giant sequoias; more than 93 percent of giant sequoia in the Sierra Nevada mountain range are in exceptional drought conditions.

Giant sequoia and coast redwood treeswhich together share the designation of Californias state treehave endured for millennia, and conservationists like Nelson hope they will stick around for millennia to come, even with man-made global warming and climate change.

To that end, the Save the Redwoods League funded a multiyear project to sequence the genomes of both the giant sequoia (Sequoiadendron giganteum) and the coast redwood (Sequoia sempervirens). Researchers at the University of California, Davis, Johns Hopkins University, the University of Connecticut, and Northern Arizona University published the coast redwood genome this month, after completing and publishing the giant sequoia genome last year.

The first step in understanding how everything works, whether its your refrigerator, or your car, or a genome, is having a parts list, is it not? said David Neale, plant sciences professor emeritus at UC Davis and lead author on the new coast redwood genome research. There was no parts list for these trees. So thats what weve accomplished, in the very earliest phases of this research, is to sequence the genomes and get a list of all the parts. Now the work begins, the good stuff begins, is learning how those parts work together to make a redwood tree a redwood tree, and a giant sequoia tree a giant sequoia tree, and why there are differences among individuals within species.

By comparing the coast redwood genome to other species of conifers, the researchers found a number of stress response genes, which could contribute to the trees longevity, including those involved in fungal disease resistance, detoxification, and physical injury/structural remodeling.

Conservationists can use this information in several ways. Inbreeding among trees is not unlike inbreeding within human populations, and it can have serious consequences, but if conservationists dont know what trees are present in a grove, they cant prune or plant with diversity in mind. This work will help give them the tools to do that.

It will also help to identify the genetic traits that might do best in warmer, dryer climates, because thats the direction California is headed.

What are the genes or combination of genes that can help trees respond to drought, respond to pests and pathogens, respond to rising temperatures? said Nelson, listing out some of the questions she hopes this research can answer. Theres both a focus on genetic diversity in retaining the widest suite of possible responses, and identifying what is it that helps trees respond to climate threats.

Neale said part of his research on redwoods has involved collecting 100 samples of individual trees of each species and growing clones of those trees from cuttings in a common garden to study how different trees grow under the same conditions. Researchers can then compare the growing conditions in the greenhouses to the average temperatures and rainfall where the original trees were located and see how a tree found in a generally cool, wet spot grows in comparison to a tree from a higher, drier location. Once the environment has been controlled, any differences in plant growth and expression can be attributed to genetic differences.

We are looking at whats the most locally adapted, and then what would be the most locally adapted, said Nelson.

Nelson said that as they are selecting seeds to raise in a nursery and plant in the wild later, they are looking for species that are both adapted to the local environment now, and those that are likely to be adapted for the environment 1000 years in the future, 2000 years in the future. That is, after all, how long these trees could live. For example, plants in the northern hemisphere are generally migrating north and up in elevation in response to climate change. So researchers are looking to plant trees that would previously have previously been found 500 feet lower in elevation, where temperatures would have been warmer.

What researchers learn about the coast redwood and giant sequoia may also inform other genetic research. Coast redwood [and giant sequoia are] not a classic model like Arabidopsis for genetic research, however, discoveries made in redwood might well inform the basic genetic system that underlies all plant adaptation to the environment, said Neale.

While it might seem like this work is all about charismatic megaflora, saving redwood trees has significant implications for climate change mitigation. In 2016, researchers found that coast redwood forests sequestered more than twice the amount of carbon as other forests. And both species of trees play important roles in their respective ecosystems, particularly coast redwoods, which help prevent erosion and protect the land-ocean boundary, which has trickle down benefits for salmon and other species.

A lot of the newspaper articles right now about giant sequoia are about existential threat, said Nelson. Were talking about extinction threat; thats what were looking at and need to respond to now.

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O redwood tree, o redwood tree, can tree genetics save thee? - Bulletin of the Atomic Scientists

Aging is inevitable, and goes along with many changes in cells, tissues, and organsincluding DNA damage, mitochondrial dysfunction, and telomere loss. But why we age in the first place and what drives these changes is still unknown. A study published December 15 in Science Advances suggests a possible answer, linking the increased activity of genes lacking long stretches of C and G bases with degeneration and aging.

As cells age, the architecture of chromatin, which packages DNA, unravels. Samuel Beck, a computational biologist at MDI Biological Laboratory, says he and his colleagues set out to explore whether these structural changes contribute to the degenerative changes also associated with aging. Specifically, the researchers focused on stretches of C and G bases called CpG islands (CGI). CGI are present in the promoters of around 60 percent of mammalian genes, termed CGI+genes, but absent in the remaining 40 percent, called CGI- genes.

These CGI- genes typically lie silent in a densely-packed form of chromatin known as heterochromatin. Heterochromatin attaches to the nuclear lamina, which lines the inner nuclear membrane. As cells age, the nuclear lamina weakens and frees the heterochromatin, which loosens, allowing previously silenced genes to be expressed.

Previously, Beck and his colleagues showed that heterochromatin formation only regulates the expression of CGI- genes, while CGI+ genes are silenced through another mechanism called repressive Polycomb bodies. In the new work, our hypothesis was that aging, and its associated chromatin architecture disorganization, results in dysregulation of genes lacking CpG islands, says Beck. Looking at gene expression in the kidneys and hearts of a mouse population generated by breeding eight inbred strains with one another, which mimics the complexity of genetics in the human population, the team found that CGI- genes tend to be upregulated in aged tissues. In some mice, CGI- genes in the kidneys were upregulated, while other mice of the same chronological age didnt show this misexpression. When the researchers took a closer look, they found that mice with upregulated CGI- genes had a higher incidence of renal dysfunction. Misexpression of CGI- genesmeaning that theyre expressed when they shouldnt beis associated with the physiological deterioration of aging, Beck says.

Looking further into the link between chromatin architecture and CGI- gene misexpression, the researchers turned to a receptor called Lamin B that tethers heterochromatin to the nuclear envelope. In mice with a nonfunctional Lamin B receptor, they observed looser heterochromatin and CGI- gene misexpressionin other words, nuclear architecture disruption and heterochromatin decondensation lead to CGI- upregulation, says Beck. The team is investigating whether it also works the other way around, with upregulation of CGI- genes causing or facilitating chromatin decondensation. If so, CGI- genes could be targeted in an attempt to reverse aging, says Beck, who, in further work, has a patent pending for an inhibitor of CGI- gene misexpression.

This is a strong descriptive study showing an association between heterochromatin disruption and the activation of genes devoid in CGI promoters (CGI-), writes University of Edinburgh geneticist Tamir Chandra, who was not involved in the study, in an email to The Scientist.

Our hypothesis was that aging, and its associated chromatin architecture disorganization, results in dysregulation of genes lacking CpG islands.

Samuel Beck, MDI Biological Laboratory

In further experiments, Beck and his team analyzed why some CGI- genes are misexpressed during aging while others are not. They homed in on the genomic landscape, which, within a cell, can be subdivided into euchromatic and heterochromatic domains. Euchromatic domains tend to harbor more CGI+ genes and heterochromatic domains more CGI- genes. When inactive CGI- genes are within broad heterochromatic domains, they are densely and broadly condensed. When inactive CGI- genes are within broad euchromatic domains, they are somewhat less densely and locally condensed, writes Beck in an email to The Scientist.

Unexpectedly, in mouse cells, CGI- genes located within heterochromatic domains were rarely misexpressed during aging, while CGI- genes forming local heterochromatin within largely euchromatic domains were overexpressed, Beck adds. We initially thought CGI- genes within both domains would be activated, however, it was not the case. CGI- genes within euchromatic domains, which are generally inactivated by local (and weak) heterochromatin formation, are frequently activated upon heterochromatin decondensation during aging. However, CGI- genes within heterochromatic domains that are densely condensed are rarely activated.

In their previous study, the authors found that CGI- genes are directly regulated by local binding of transcription factors, while CGI+ genes are not. Accordingly, when they looked for sites where transcription factors might bind in euchromatic and heterochromatic domains, they found that CGI- genes within euchromatic domains have more transcription factor binding sites compared to CGI- genes within heterochromatic domains. Additionally, CGI- genes within euchromatic domains that are upregulated during aging contain more binding sites than genes that are not upregulated. Beck interprets these observations as showing that heterochromatin decondensation during aging allows easy access of transcription factors to DNA. So CGI- genes that are more susceptible for transcription factor binding (i.e., with many motifs) are more frequently activated when heterochromatin disappears. However, this is still speculation, as the authors didnt test this explanation further. Further investigation as to why it is not CGI- genes located in [heterochromatin] that are affected by the disruption would be interesting, writes Chandra.

The researchers also investigated whether CGI- genes are connected to whats known as cellular identity. Cells making up the heart, muscles, kidneys, or other organs usually express different genes to carry out their functions. As cells age, they also lose this cellular identity, and the researchers wondered if misexpression of CGI-genes could help explain why. Analyzing aged mouse kidneys, Beck and his team saw that genes typically expressed in the spleen, intestine, eye, and liver start to be expressed in aged kidneysand the majority of these genes were CGI- genes. That is one way how aged cells lose their identity, suggests Beck.

Aged cells also secrete signals in an uncontrolled way, but what triggers this secretion is not yet known. Analysis of the products of CGI- genes in mouse kidneys and hearts indicated that many encode secreted proteins, including cytokines, chemokines, growth factors, and proteases. Proinflammatory secretory CGI- genes were misexpressed in cells in which the nuclear and chromatin architecture was disrupted. According to the authors, this indicates that the secretory phenotype of aged cells is linked to disruption of the nuclear architecture and resulting upregulation of CGI- genes.

This study pinpoints and defines the specific set of genes that are aberrantly activated during aging and the consequences, geneticist Weiwei Dang from Baylor College of Medicine, who was not involved in the study, writes in an email to The Scientist.However, he sees several limitations to the study, including that most of the data presented (with some exceptions) are association data between aging and transcription, without further digging into the underlying causes of these changes during aging, and that key regulators that distinguish between CGI+ and CGI- genes remain to be identified or investigated.

Dang also notes a lack of potential aging intervention strategy based on these findings. However, Beck suggests that if overexpression of CGI- genes does turn out to drive chromatin decondensation, then inhibiting CGI- gene expression could become such a strategy.

More here:
Aging in Mice Linked to Misexpression of Class of Genes - The Scientist

Multiple scientists and experts are weighing on what Americans should expect from the omicron variant of the coronavirus over the next few weeks.

Dr. Stephen Goldstein, professor at the Eccles Institute of Human Genetics at the University of Utah, told Salon that cases will rise in the next few weeks to peak levels.

Dr. Monica Gandhi, infectious disease doctor and professor of medicine at the University of California-San Francisco, told Salon that omicron is more transmissible and will cause a wave of new infections.

Its clear from these comments that the omicron variant is spreading and will continue to do so as we move through winter. Its unclear if the strain is less virulent meaning it causes less severe symptoms on its own or if people are more immune to the coronavirus by now, creating less severe symptoms.

Either way, the Centers for Disease Control and Prevention recently predicted a new surge of omicron cases will impact the U.S. by January 2022, according to The Washington Post.

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The future of omicron variant: Scientists predict whats next - Deseret News

By which routes did modern man arrive in Europe? A book reports on the latest findings.

What routes did Homo sapiens take on his way from Africa to Europe and Asia in the previous millennia? The climatic conditions changed, and with them the living conditions. The advance was hampered in some places by deserts, in others by dense forests. Over the past twelve years, a team of researchers within the framework of the Collaborative Research Center 806 Our Way to Europe unraveled the complex interplay of cultural innovations and environment that shaped migrations. After completion of the interdisciplinary joint project, the researchers now present a book with the most important findings under the leadership of the Universities of Bonn and Cologne.

The cradle of man is in Africa this has been known for half a century. A decade ago, scholarly discussion was still dominated by the idea that a small group of Homo sapiens migrated from Africa to Europe about 70,000 years ago. Through anatomical and intellectual superiority, this group is said to have displaced archaic local populations as it advanced, leaving Homo sapiens as the only genetic branch of humanity to survive.

Varves in a drill core from Lake Van, Turkey.These are lighter and darker layers in lake sediments that are deposited over the course of a year. Credit: Thomas Litt/University of Bonn

This notion has changed fundamentally since it became clear that Neanderthals contributed at least a small part to the genome of Homo sapiens, says paleobotanist Prof. Dr. Thomas Litt of the University of Bonn, principal editor of the book and deputy spokesman for the Collaborative Research Center. Genetics doesnt quite tell the same story or a different part of the story as paleontology and archeology. The team therefore endeavored to better understand this controversial picture by analyzing information on the nature and environment, as well as the role of culture, of this prehistoric population dynamic. The researchers focused on different time periods: from the emergence of modern humans, their dispersal, the repopulation of Ice Age Europe, Neolithic settlement, and the migration of settled societies.

The new findings show that not only a migration wave, but several African Homo sapiens populations followed a journey of up to 5,000 kilometers to Europe and Asia. Improved radiometric dating of Homo sapiens fossils further suggests that the area of origin of modern humans includes not only East Africa, but also South and Northwest Africa. The time scale of Homo sapiens now extends back to 300,000 years. Prof. Litts team investigated when and where migration corridors or barriers existed from a paleoecological and paleoclimatological perspective.

Until now, science assumed that there were two possible main routes modern man could have taken to Europe: The western via the Strait of Gibraltar and the eastern via the Levant. Despite the short distance across the Strait of Gibraltar, in the past twelve years researchers were unable to find any evidence of direct cultural contact between Morocco and the Iberian Peninsula or evidence of crossing the strait during the Paleolithic. This is one of the big question marks in the history of human settlement in the western Mediterranean, Litt says of this surprising finding. Evidently, the Strait of Gibraltar had been more of a barrier at the time due to strong ocean currents.

This leaves the Levant, the only permanent land bridge between Africa and Eurasia, as the key region as a migration route for modern humans, says Litt. His research group conducted intensive research on drill cores, for example from the Dead Sea or the Sea of Galilee, in which plant pollen is preserved. This allows changes in vegetation cover to be identified and environmental and climatic conditions to be reconstructed. Litt: These data illustrate that the Levant could only have served as a corridor when, under more favorable conditions, for example, neither deserts nor dense forests impeded the advance.

For a total of twelve years, the interdisciplinary research team from archeology, geosciences, soil science, ethnology and geography in the Collaborative Research Center 806 Our Way to Europe deciphered the migrations of Homo sapiens. Around one hundred researchers were involved and many hundreds of scientific papers were published. In addition to the Universities of Cologne and Bonn, RWTH Aachen University and numerous cooperation partners from the USA, Africa, the Middle East, and Europe were also involved. The main results are now summarized in the 372-page book jointly edited by the paleobotanist Prof. Dr. Thomas Litt (Bonn), the prehistorian Prof. Dr. Jrgen Richter and the geography didactician Prof. Dr. Frank Schbitz (both University of Cologne). The book should be attractive and relevant to all readers interested in understanding the prehistory of our own species, its migratory routes, and motivations for migration triggered by complex interactions of its culture and environment, says Litt.

Publication: Thomas Litt, Jrgen Richter, Frank Schbitz (eds.): The Journey of Modern Humans from Africa to Europe Culture-Environmental Interaction and Mobility, Schweizerbart Science Publishers, 372p., EUR 39.90.

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Out of Africa: The Path of Homo sapiens By Which Routes Did Modern Man Arrive in Europe? - SciTechDaily

A decline in the use of the word "race" in papers on human genetics reflects a growing understanding of race as a social construct. But other trends may point to ongoing uncertainty about how to discuss different populations.

What to know:

Human geneticists have moved away from using the word "race" to describe populations, a study recently published in The American Journal of Human Genetics (AJHG) shows.

Researchers examined the text of all 11,635 articles published between 1949 and 2018 by the AJHG. While the word "race" appeared in 22% of papers in the first 10 years of the paper's publication, it was used in just 5% of papers in the last 10 years.

This decline points to the current understanding in science of race as a social construct and a desire to move away from past research that erroneously conflated genetics with racial categories, according to lead author Vence Bonham, JD, the acting deputy director of the National Human Genome Research Institute.

The study also found that the alternative and sometimes more ambiguous terms "ethnicity" and "ancestry" have increased over time, which may suggest that geneticists are still struggling to find terms to accurately describe populations.

A The National Academies of Science, Engineering, and Medicine has recently formed a committee to produce a consensus report on the use of the word "race" and other terms descriptive of populations in health disparities research.

This is a summary of the article "Human geneticists curb use of the term 'race' in their papers" published by Science on December 2. The full article can be found on science.org.

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Geneticists Have Reduced Use of the Term 'Race' in Papers - Medscape

BOULDER, Colo., Dec. 09, 2021 (GLOBE NEWSWIRE) -- In a new study published in Nature Genetics, scientists at deCODE genetics, a subsidiary of Amgen, used SomaLogics (NASDAQ: SLGC) SomaScan Assay to measure blood proteins in 35,559 Icelanders and mapped them to 27 million genetic sequence variants. Using this vast amount of proteomic data, these researchers hope to demonstrate that combining protein measurements at population scale with genetic data on disease will dramatically impact understanding of human diseases and potential drug targets. This new study was the largest proteomic study published to date with 170 million protein measurements.

Less than 10% of human disease is driven by genetics. Plasma proteomics, the study of blood proteins, can help bridge the gap between genomics and disease discovery. This paper found that linking genes to proteins, and then to diseases can show patterns between the factors that cause a disease and the factors that are a consequence of a disease. This process may give a roadmap of how diseases develop and offer potential drug targets.

In this study, the plasma levels of 4,719 blood proteins were tested for genetic associations with 373 diseases and traits, producing 257,490 of these associations. SomaLogics SomaScan Assay was used to find genetic variant-protein target associations, called protein quantitative trail loci or pQTLs. In the study, 94% of the proteins measured using the SomaScan Assay showed an associated pQTL, resulting in more than 18,000 pQTLs. Ninety-three percent of these pQTLs are considered novel. The study also identified 938 genes encoding as potential protein drug targets for various diseases.

Our SomaScan Assay offers the ability to measure and identify the largest percentage of the human proteome at commercial scale on the market today and it proved to be exquisitely specific in this study, said SomaLogic Chief Executive Officer Roy Smythe, M.D. We hope that this study, and more like it, will help to provide the vital information that can be added to genetic data to create a more comprehensive understanding of human biology, and increasingly power more effective treatments for human disease.

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About SomaLogicSomaLogic (Nasdaq: SLGC) seeks to deliver precise, meaningful, and actionable health-management information that empowers individuals worldwide to continuously optimize their personal health and wellness throughout their lives. This essential information, to be provided through a global network of partners and users, is derived from SomaLogics personalized measurement of important changes in an individuals proteins over time. For more information, visit http://www.somalogic.com and follow @somalogic on Twitter.

Forward Looking Statements Disclaimer This press release contains certain forward-looking statements within the meaning of the federal securities laws with respect to the proposed business combination between SomaLogic and CM Life Sciences II and otherwise, including statements regarding the anticipated benefits of the business combination, the anticipated timing of the business combination, expansion plans, projected future results and market opportunities of SomaLogic. These forward-looking statements generally are identified by the words believe, project, expect, anticipate, estimate, intend, strategy, future, opportunity, plan, may, should, will, would, will be, will continue, will likely result, and similar expressions. Forward-looking statements are predictions, projections and other statements about future events that are based on current expectations and assumptions and, as a result, are subject to risks and uncertainties. Forward looking statements do not guarantee future performance and involve known and unknown risks, uncertainties and other factors. Many factors could cause actual future events to differ materially from the forward-looking statements in this press release, including factors which are beyond SomaLogics or CM Life Sciences IIs control. You should carefully consider the risks and uncertainties described in the Risk Factors section of the CM Life Sciences IIs registration statement on Form S-4 (File No. 333-256127) (the Registration Statement) and the definitive proxy statement/prospectus included therein. These filings identify and address important risks and uncertainties that could cause actual events and results to differ materially from those contained in the forward-looking statements. Forward-looking statements speak only as of the date they are made. Readers are cautioned not to put undue reliance on forward-looking statements, and SomaLogic and CM Life Sciences II assume no obligation and do not intend to update or revise these forward-looking statements, whether as a result of new information, future events, or otherwise. Neither SomaLogic nor CM Life Sciences II gives any assurance that either SomaLogic or CM Life Sciences II or the combined company will achieve its expectations.

SomaLogic Contact Emilia Costales 720-798-5054ecostales@somalogic.com

Investor ContactLynn Lewis or Marissa BychGilmartin Group LLCinvestors@somalogic.com

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SomaLogics SomaScan Assay used in largest proteomic study to date, bridging the gap between genomics and disease - Yahoo Finance