Category Archives: Human Genetics

GENE & CELL MEDICINE LTD located in Israel and Singapore started a new project:LifeBank Chain (LBC). The project LBC plans to build a genetic and cell data collaboration platform.

Genetic research seeks to understand the process of trait inheritance from parents to offspring.Human genetic research is revealing the nature of human bioinformatics and giving scientists a powerful approach to study various health issues of human life.

Cell research focuses on stem cell and immune cell therapies, which are an extremely promising approach for the treatment of many diseases with an immune component including cancer, autoimmune disease, and chronic inflammation.

The wide applications of these new biological technologies in the medical field greatly reshaped the traditional pharmaceutical industry, whose focus was not only put on the treatment of disease as before but also on gene diagnosis and prevention, which opened the door to the world of a personalized and precise medicine.

Blockchain is an emerging technology that has attracted increasing attention from both researchers and practitioners. The functionalities of blockchain technology and smart contracts provide an opportunity over the large gene and cell data to support genetic and cell data integrity and security while giving patients control over their own data.

LBC plans to build a genetic and cell data collaboration platform incorporating an extensible cross-chain service system based on individual and institutional nodes. The platform product service layer abstracts all typical kinds of gene and cell blockchain applications and provides the full functions and implementation framework of typical applications.

The goal ofLifeBank Chain (LBC) is to establish a global-level service platform for sharing and utilizing human genetic and cell data through secured blockchain technologies.The LBC blockchain is designed to provide genetic and cell research industry partners with enterprise-level blockchain infrastructure, industry solutions, and secure, reliable, and flexible blockchain services. LBC will work together with medical practitioners to provide full-solution ancillary reagent services and provide flexible and pioneering tools to simplify therapy workflow at every step of the medical process.

LBC will form a professional and shared social organization LBC Life Alliance inviting life technology companies, scientific research institutes, medical institutions, etc. to jointly solve medical, health, disease, and public health problems, and jointly build the application standards of gene and stem cell medical technology on the blockchain, and contribute to the cause of human health.

LifeBank Chain enables healthcare professionals to manage the medical data and do research in an auditable, transparent, and secure way on LBCs distributed network. LBC continues to closely monitor the evolution of genetics and cell therapy in different medical subspecialties around the world.

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LifeBank Chain (LBC) Focuses on Research and Development in the Field of Genetics and Cell Science - Markets Herald

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., who is the deputy director of the Wilmot Cancer Institute and the Robert and Dorothy Markin Professor of Biomedical Genetics at the University of Rochester Medical Center and 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

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

Missing insulation: Mutations in the gene MYT1L disable a transcription factor important for cells that make myelin, which enshrouds nerve fibers.

Biophoto Associates / Science Source

A variety of traits, including developmental delay and intellectual disability, characterize people with mutations in the autism-linked gene MYT1L, according to a new study. The gene encodes a transcription factor important for cells that make myelin, which insulates nerve cells and is deficient in some forms of autism.

The work, published 8 November in Human Genetics, represents the most detailed study of the traits associated with MYT1L mutations to date.

We wanted to gather more cases to bring a clearer clinical and molecular picture of the condition for lab scientists, clinicians and also for patients and families, says study investigator Juliette Coursimault, a physician-researcher in the genetics department at Rouen University Hospital in France. She and her co-researchers described 62 people, whereas previous literature included only 12 cases.

The new characterization will benefit clinicians diagnosis and treatment strategies when a patient with MYT1L mutation arrives in their clinic, says Brady Maher, a lead investigator at the Lieber Institute for Brain Development at Johns Hopkins University in Baltimore, Maryland, who was not part of the study.

The researchers identified and reviewed data for 22 people with MYT1L mutations who had been described in the academic literature, and collected clinical and molecular data from an additional 40 people, aged 1 to 34 years old, with likely or confirmed pathogenic variants of MYT1L. They recruited the participants through Rouen University Hospital and data-sharing networks such as GeneMatcher, which connects clinicians and researchers.

Almost everyone in the cohort has global developmental delay and behavioral issues, and 70 percent have intellectual disability. Nearly 60 percent are obese, 43 percent have a clinical suspicion or formal diagnosis of autism, and 23 percent have epilepsy.

Additionally, the researchers described traits not previously linked to MYT1L mutations, including failure to thrive and feeding difficulties.

Collecting large sets of cases to understand the phenotype is essential to fleshing out our understanding of these forms of autism and intellectual disability, says Joseph Dougherty, associate professor of genetics and psychiatry at Washington University in St. Louis, Missouri, who was not involved with the study.

The participants traits were broadly similar, regardless of the type of MYT1L mutation they had, perhaps because all of the variants inactivate one of the two copies of the MYT1L and diminish the genes expression in a similar way.

Its likely that the type of MYT1L mutation works in combination with an individuals unique genetic background to determine their symptom severity, Maher says.

How MYT1L mutations lead to these traits remains unknown. Of particular concern is the prevalence of obesity among people with MYT1L-associated conditions, the researchers say.

Mapping out the pattern of weight gain in overweight and obese participants revealed a median age of rapid gain at 3 and a half years. These children were able to normalize their weight once their parents started to monitor their food intake, which suggests that early-onset obesity may be a characteristic of MYT1L-associated neurodevelopmental conditions and that these children benefit from early intervention, the researchers say.

Important future steps involve modeling MYT1L-associated neurodevelopmental conditions in cell, tissue and animal models, the researchers say.

If we understood which common genetic variants provided resilience or protection, we might be able to develop therapies based on these insights, Maher says.

Cite this article: https://doi.org/10.53053/DGGE3322

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Cluster of traits tied to rare mutations in autism-linked gene | Spectrum - Spectrum

image:Mouse one-cell embryo showing two pronuclei: the human version is similar, and their busy preparation for future development remains a mystery. view more

Credit: Perry Lab, University of Bath

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

For further information, please contact Professor Tony Perry at the University of Bath, email perry135@aol.com or the University of Bath press office at press@bath.ac.uk or (+44) 1225 383841. To speak to Dr Giles Yeo, email Amy Hall: amy@catalysthcm.com. To speak to Dr Tex VerMilyea at Ovation Fertility, email Amy Hall: (+1) 214.893.8214

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

Ovation Fertility 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.

Human embryos

Human embryonic genome activation initiates at the one-cell stage

21-Dec-2021

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

Our cells are packed with unrealized potential. Almost every human cell contains the genetic information it needs to become any other kind of cell. A skin cell, for example, has the same genes as a muscle cell or a brain neuron, but in each type of cell only some of those genes are switched on, while others remain silent. Its a little like making different meals out of the same ingredients cupboard. If we understand the recipe behind each type of cell, then theoretically we can use this information to engineer every single cell type in the human body.

That is Mark Kotters goal. Kotter is the CEO and cofounder of bit.bioa Cambridge, UK, based company that wants to revolutionize clinical research and drug discovery by producing precisely engineered batches of human cells. Basic scientific research into new drugs and treatments often starts with tests in mice, or in the most widely used human cell lines: kidney cells and cervical cancer cells. This can be a problem, because the cells being experimented on may have major differences to the cells that a candidate drug is supposed to target in the human body. A drug that works in a mouse may turn out not to work when it's tested in humans. There is no mouse on this planet that has ever suffered from Alzheimers, it just doesnt exist, Kotter says. But testing a potential Alzheimers drug on a human brain cell engineered to have signs of Alzheimers disease could give a much clearer indication of whether that drug is likely to be successful.

Every cell type has its own little program, or postcodea combination of transcription factors that defines it, says Kotter. By inserting the right program into a stem cell, researchers can activate genes that code for these transcription factors and turn a stem cell into a specific type of mature cell. Unfortunately, biology has a way of fighting back. Cells often silence these genes, stopping the transcription factors from being produced. Kotters solutiondiscovered as part of his research at the University of Cambridgeis to insert this program in a region of the genome thats protected against gene silencing, something Kotter refers to as a genetic safe harbor.

Bit.bio currently sells two different reprogrammed cell lines: muscle cells and a specific kind of brain neuron, but the plan is to create bespoke cell lines for use in the pharmaceutical industry and academic research. What were doing with our partners in the industry now is to create genetic modifications that are relevant for diseases, Kotter says. He compares this approach to running software on a computer. By inserting the right bit of code into a cells genome, you can control how that cell behaves. That means that we can now run programs, and we can reprogram human cells, Kotter says. The cell reprogramming technology could also go well beyond model cell lines and help develop whole new kinds of treatment, such as cell therapy.

In some cell therapies, a patients own immune cells are grown outside of their body before being modified and inserted back into it to help fight a diseasea long and expensive process. One kind of cell therapy used to treat young people with leukemia costs more than 280,000 ($371,400) per patient. Bit.bios chief medical officer Ramy Ibrahim says that the firms technology could help drive down the cost of cell therapy and make it easier to manufacture immune cells at a large scale. Having abundant numbers of the right cell types that we can now make edits to, I think will be transformational, he says.

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This Startup Is Makingand ProgrammingHuman Cells - WIRED

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.

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

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

Researchers from Monash University in Melbourne have developed a method for determining which genes are "in play" in causing cardiac abnormalities, and the technique not only confirmed well-known congenital heart disease genes, but also discovered 35 new genes not previously suspected in the disease.

Published in Genome Biology, the goal of the study was to find congenital heart disease genes, because nearly 1% of the babies born have congenital heart disease, and it is the leading cause of death in newborns, Travis Johnson, from Monash University's School of Biological Sciences, told BioWorld Science.

"Genetics have an awful lot to do with congenital heart disease, and we really have very few genes that we know of that contribute to this disease. Our goal was to try and find more potential candidate genes that could be involved in causing congenital heart disease," said Johnson, who co-led the work with Mirana Ramialison, from Monash University's Australian Regenerative Medicine Institute and the Murdoch Children's Research Institute.

The current conventional approach focuses on screening genes that are present in the heart only, he said, which often overlooks genes that are present in other tissues as well.

Despite the wealth of knowledge from these conventional gene discovery studies, the origin of congenital heart disease is unknown in 80% of cases, suggesting that several determinants of heart disease, including genetic, are yet to be identified, study authors said.

"Making the heart is almost like a symphony," Johnson said. "You need all the different instruments to play their role," he said, likening the genes to instruments.

"We looked at the sheet music -- what was switched on and when it was switched on -- and that gave us a long list of genes that could be causing heart disease.

"We found a lot of the genes that are already known to be involved in heart disease, which was really nice validation, but we found more than 1,000 other genes that are quite good candidates that have not been looked at before," said Johnson, who is a fly geneticist.

He teamed up with Ramialison, who developed bioinformatic software that mined existing databases to look for genes that were not only switched on in the heart during development but also at genes that are switched on in other places but that also work in the heart.

The resulting computational pipeline identified not only genes specific for the heart but genes that may also be associated with other organs such as the liver or kidney.

"These could comprise many of the missing congenital heart disease genes, but have been, to date, discounted because they are not unique to the heart," Ramialison said.

Fruit fly model

The researchers used the fruit fly, Drosophila melanogaster, as a testing model to determine some of the functional impacts of these novel genes. Drosophila is a well-established model organism to understand the genetic mechanisms of many human diseases, Johnson said, largely because about 75% of human disease-causing genes are found in the fly in a similar form.

"The fly has a heart muscle, and we looked at all the fly versions of the gene that we pulled out of the software pipeline. Because flies are easy to manipulate genetically, we used our genetic tools to systematically go through and knock them all out just in the heart.

"We asked which ones affect the development of the fly heart, and we found that more than 70% of them affect the development of the fly heart. We did that as a functional validation of genes. It's one thing for a computer program to spit out genes, but it's another thing to go into the lab and test them in an animal," he said.

The fly studies revealed "a long list of high-quality candidate genes for causing heart abnormalities in humans, giving real insight into just how susceptible this organ is to genetic mutations."

"All in all, we tested more than 35 of the genes in flies. As you can imagine, there's still a huge list of genes that are highly likely to be involved in forming the heart in utero."

"With this pipeline, we retrieve 76% of the known cardiac developmental genes and predict 35 novel genes that previously had no known connectivity to heart development. Functional validation of these novel cardiac genes by RNAi-mediated knockdown of the conserved orthologs in Drosophila cardiac tissue reveals that disrupting the activity of 71% of these genes leads to adult mortality. Among these genes, RpL14, RpS24 and Rpn8 are associated with heart phenotypes," study authors note.

"The pipeline enabled the discovery of novel genes with roles in heart development. This workflow, which relies on screening for noncoding cis-regulatory signatures, is amenable for identifying developmental and disease genes for an organ without constraining to genes that are expressed exclusively in the organ of interest," they said.

Next steps

The challenge now is to determine which genes are involved, when they are not working, and whether genetic screening can determine if a child is at risk of having a congenital heart defect.

"We now have a long list of genes and can sift through genetic data," Johnson said, noting that these genes are the ones most likely to be the important ones to look at, because the team narrowed it down to the "cream of the crop" for its validation strategy.

The research opens the way for more accurate prenatal genetic testing for congenital heart disease, and the method can now be applied to look at other organ development diseases, he said.

"But the heart is the top of the list because the heart is very sensitive to genetic noise -- it's the most important symphony to get right. We've been able to add a lot of genes to that list that will help people predict who is more likely to develop congenital heart disease.

"We're hoping that other researchers will take notice and start investigating the functions of these genes or potential roles in congenital heart disease."

More:
Researchers discover more than 1300 genes linked to congenital heart disease - BioWorld Online

As Covid-19 vaccinations increase globally, life is getting back to normal. However, it's no longer the world we experienced before the pandemic. The long-term nature of this global crisis has changed customer needs and daily lifestyles. This will, in turn, change what I expect the world to look like in 2022 and beyond. Let's review the top 10 technology and business trends that we'll likely encounter in the coming year.

Momentum in Life Science Technologies

The life science industry comprises pharmaceuticals,biotechnology, environmental sciences, biomedicine, nutraceuticals, neuroscience, cell biology, and biophysics. Partially because ofincreased investments in mRNA vaccine technology and high-performance Covid-19 testing, 2021 has driven great innovation in life science technologies.

Examples of this innovation include the mRNA-based vaccines developed by Pfizer-BioNTech and by Moderna. Recent Covid drug developments by Merck have also pushed the life science industry forward rapidly.

Looking ahead, I expect we'll see strong movement in the several life science sectors, including advanced research; application of robotics technology; artificial intelligence (A.I.) tools; use of cloud technology; the improvement of drug testing speed; integration of genetic information; and usage of gene technology. I also foresee the development of personalized medicine through advancements in genetics technology. The startup 23andMe, for example, helps people access, understand, and benefit from the human genome.

Networking and Interconnectivity: Expansion of 5G-6G and Satellite-Based Internet Usage

As remote working becomes commonplace, internet reliability becomes more vital than ever. The internet of things (IoT) makes the internet a more integral part of our lives, and developments at all network levels will continue to drive research and push the internet economy forward.

According to Cisco's Visual Networking Indexforecast update for 2018, there will be 1.4 billion more people using the internet by 2022, compared with 3.4 billion users in 2017. This equates to almost 60 percentof the global population, assuming a population of eight billion by 2022. By then, internet users are expected to consume 4.8 zettabytes of data per year, 11 times the amount of IP traffic generated in 2012, with 437 exabytes.

While 5G may be in its infancy, we'll see an increased focus on 6G in 2022. China started research into 6G in 2018. By late 2020, the country had launched a satellite to test terahertz signal transmission. Huawei and ZTE were involved. The U.S. also started 6G research in 2018 with the Federal Communications Commission (FCC) opening higher frequency spectrum for experimental use. A Next G Alliance was started in 2020, with companies on board including Apple, AT&T, and Google. Korea, Japan, and some European countries have started looking into 6G seriously, and we expect to see more announcements in 2022.

High-Performance Computing Becomes Mainstream

Given the recent growth of big data-based research and analysis and cloud-based computing, I expect high-performance computing usage to surge in 2022. From drug discovery to cancer research to space exploration, high-performance computing will become increasingly important, and quantum computing technology needs to keep up with business demand.

We've already seen massive development in quantum computing space by players including Google, IBM, Microsoft, Amazon, and Alibaba. Startups such as Rigetti Computing, D-Wave Systems, ColdQuanta,1QBit, Zapata Computing, and QC Ware have exceeded the industry expectations in their technology and their growth.

I expect rapid progress in quantum computing during 2022, because the high demand for larger machine power is going to accelerate development in this sector.We'll likely see announcements of large qubit developments in the new year. Commercial quantum computing will soon be within our reach, and new breakthroughs will occur at an accelerated pace.

Continued Growth in Artificial Intelligence, Big Data Analytics, and Cloud Computing

A.I. has become an integral part of our lives. From improvements to personalization, ranking search results, recommending products, and understandingand controlling devices tobuilding better models of the environment to automatingindustry, we see the application of artificial intelligence everywhere as we look toward 2022.

Organizations are using predictive analytics to forecast future trends. According to a report published by Facts & Factors, the global predictive analytics market is growing at a compound average growth rate of around 24.5 percentand is expected to reach $22.1 billion by the end of 2026.

We will also see massive growth in cloud computing. By 2022, the cloud will be more entrenched and more computing workloads will run on the cloud. The internet of things will push this space in a bigger way, for sure. According to predictions from Gartner, global spending on cloud services is expected to reach over $482 billion in 2022, up from $314 billion in 2020.

Internet Security and Privacy Dominate

As the world becomes more digital, we're seeing an increased number of personal and organizational cyberattacks around the world. Several corporations have been the target of major cyberattacks in recent days, and businesses have become more vulnerable to destructive attacks, in part because ofincreased remote work giventhe pandemic.

During 2022, I expect that we'll see cyberattacks across sectors, and we will see the industry take a variety of counteractive measures. Defending against cyberattacks will include educating individuals so they can identify and avoid network assaults, thereby safeguarding their company's image.

Applying A.I. will make robust cybersecurity protocols easier andless expensive to createand more effective than ever. Use of A.I. can enable cybersecurity to spot risks and learn the behaviors of cybercriminals, thus preventing prevent future attacks. It can also help cut down on the time it takes cybersecurity specialists to do their daily tasks.

The MetaverseWill Shine in 2022

The metaverse is a digital reality combining social media, online gaming, augmented reality, virtual reality, and cryptocurrencies to allow virtual user interaction. The metaverse may refer to anything on the internet, including all of AR's offerings. Virtual space of the future describes the metaverse, providing access to all kinds of entertainment and projects, including the opportunity to work.

We expect the metaverse to be immersive, ubiquitous, and free to access. It will be digitally focused, and potentially involves entertainment, social connection, work productivity, and behavior modification at scale. It will create an entire ecosystem for developers, apps, ads, and new digital innovations. The metaverse will facilitate convenience, consumption, and a frictionless access to services.

Only a few companies today have a real stake in the metaverse. They include ByteDance, Tencent, Facebook, Spotify, Zoom, Amazon (Twitch), Alibaba, Roblox, Bilibili, Snapchat, Kuaishou, and Huawei. Apple's wearables also point to the metaverse with AR glasses coming soon. Microsoft with Microsoft Teams and gaming is perhaps the most advanced company in the world regarding the metaverse. WeChat's ability to facilitate payments and access to a variety of services is the start of the metaversesuper apps.

As the metaverse ecosystem grows in 2022, I expect it will have a direct impact on the future of many technology sectors. These include gaming, wearables, VR and AR, collaborative productivity (Canva, Slack), consumer tech products (including AR glasses or smart speakers), social networks, educational technology, health technology, communication technology (Zoom), digital currencies, and convenience mobilization and on-demand consumption (Amazon, Meituan, Alibaba, JD.com, Shopify).

NFT Platforms Will Boom

A non-fungible token (NFT) is a digital object: computer code and data that conveys ownership of something. The property may be online:for example, virtual real estate in the digital world or special equipment in a video game. Or it could be real: real estate, a painting, or a seat at a concert. An NFT can also be a hybrid:for example, the right to decide who can rent a room in a cooperative living space. A baseball card, Ronaldo's first ball, a vintage car, or a piece of land in Central London: All are one of a kind and can be transferred to the NFT.

In 2022, we are likely to see NFTs everywhere; this includes in movies, TV shows, books, and more. NFTs are part of the digital economy and are becoming mainstream because they allow people to own something that represents a part of something bigger than themselves -- a piece of art or a character, for example. The digital economy is made up of a variety of online markets, including game economies, virtual real estate, and even social media platforms like Facebook.

Our society has changed rapidly over the past decade, especially because of the 2008 to 2009 economic crisis and the pandemic. These trends are coming together to shape a world where NFTs will beat traditional collectibles, making 2022 a tremendous year.

The Robotics Sector Will Become More Prevalent

We expect to see an increased use of robotics in everyday life during 2022. Usage will include the health care, agriculture, automotive, warehousing, and supply chain management sectors, and we will see more robotics-based automation that will continue to progress.

The Covid-19 pandemic presents both problems and opportunities forroboticscompanies in the logistics and supermarket industries. Unexpected strains on supply systems and product shortages have highlighted the need for better supply chain efficiency. It's also become obvious thatrobotsand automation providea safe means for manufacturers to keep employees socially separated yet allow the business to continue operating.

The use of robotics process automation (RPA) helps automate activities that are performed repeatedly; we expect RPA to grow in 2022 and become a standard technology for business. CIO reports that chief information officers are using RPA to free workers from boring, repetitive tasks and allow them to do more fulfilling work. Finally, we're seeing a rise in nanorobotics, tiny sensors with limited processing power. The first useful applications of these nano-machines may be in nanomedicine. Biological machines, for example, are used to identify and destroy cancer cells or deliver drugs.

Increased Urgency in the Renewable Energy Technology Sector

Climate change and dramatic news headlines are driving rapid growth in sustainable energy adoption. During the pandemic, this has been the only energy sector that has grown. According to the International Energy Agency (IEA), 40 percentmore green energy was generated and used in 2020; the agency expects continued growth in 2022. The falling costof generating sustainable energy also helps ensure that mass adoption is likely. While newer energy technologies like nuclear fusion, biofuel, and liquid hydrogen might take longer to come full circle, we look forward to serious advancements in 2022.

I also expect to see massive growth in the production and usage of solar and wind technology. Storage (battery) technologies are playing a larger role, since there will be an increased need to store renewable energy.

Blockchain Technology Prevails

Blockchain, an innovative breed of distributed ledger, enables companies to track a transaction and do business with unverified parties -- even without the assistance of financial institutions. This new capability significantly lessens business conflicts; it also adds other benefits such as append-only data structure, transparency, security, immutability, and decentralization.

Blockchain technology has enjoyed massive adoption and continues to disrupt many industries, from gaming and governance to finance. According to the International Data Corporation, companies will spend almost $6.6 billion on blockchain solutions in 2021, a 50 percentincreasefrom the previous year. This number is expected to grow beyond $15 billion in 2024. With the new rise of NFTs and themetaverse, blockchain will become more important in 2022.

Businesses are encouraged to start studying blockchain technology, since it is expected to generate significant business opportunities; Statista reports that global blockchain technology is predicted to grow to more than $23.3 billion by 2023. A notable existing blockchain deployment is that of Walmart's supply chain database application, allowing the monitoring of individual products directly to their very source, effectively elevating food supply standards. Amazon is rolling out its blockchain initiatives for 2019, which allow its Amazon Web Services clients to benefit from distributed ledger solutions.

Looking Ahead

There's little doubt that 2022 will see rapid progress in these and other technologies, as the world emerges from the Covid-19 pandemic. I see a prime opportunity for smart startups, corporations, and investors to capitalize on these emerging technology and business trends to become more successful than ever. Let's hope that the resulting innovation makes the world better for people and businesses.

The opinions expressed here by Inc.com columnists are their own, not those of Inc.com.

Read the rest here:
The Top 10 Technology and Business Trends of 2022 - Inc.