Category Archives: Transhuman News

The U.S. Food and Drug Administration has approved the first treatment for progeria, a rare and fatal pediatric disease, characterized by dramatic, rapid aging beginning in childhood. The treatment was made possible thanks in part to work at the National Institutes of Health over nearly two decades to identify and understand the function of the mutant gene and the protein it encodes (called progerin) with the goal of identifying new therapeutic drugs for the disorder.

In light of todays approval, NIH Director and Senior Investigator at the National Human Genome Research Institute (NHGRI), Francis S. Collins, M.D., Ph.D., is available to discuss his labs research activities on progeria, including its involvement in the discovery of the gene responsible for the disease, the development of a mouse model, and the demonstration that this drug class could provide benefit.

Progeria, also known as Hutchinson-Gilford progeria syndrome, is a rare, multisystemic disease that causes premature aging and premature death in children. Progeria is caused by a genetic mutation in the LMNA (lamin A) gene, which helps maintain the normal structure and function of a cells nucleus. About 400 children worldwide have been diagnosed with progeria.

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Decades of NIH research help lead to first FDA-approved treatment for progeria - National Human Genome Research Institute

Deep inside your cells, DNA provides the instructions to produce proteins, the essential molecules that grow and maintain your body.

RNA is the intermediary nucleic acid that carries these instructions from DNA to ribosomes, where proteins are produced within the cell. But in humans and in plants, only a tiny fraction of DNA produces the RNA that carries out protein-building instructions. In humans, almost 98% of the genome does not encode proteins. However, it often gives rise to RNA that does not produce proteins, called noncoding RNA. So what does this portion of the genome do?

Over the years, studies have found that more than 80% of the genome may be involved in transcription, or producing noncoding RNA, said Andrzej Wierzbicki, a professor in the University of Michigan Department of Molecular, Cellular and Developmental Biology. So the dilemma was: Is all this noncoding RNA functional? Is it important for something? Or is it just noise of the process of transcription or an error of detection methods?

Now, research led by Wierzbicki shows that in plants, a portion of this noncoding RNA may play an essential role in protecting the integrity of the genome. This portion of noncoding RNA is produced from transposons, rogue pieces of genes that jump around within DNA, inserting themselves haphazardly and causing genetic diversity. Sometimes this diversity is beneficial, aiding evolution, says Wierzbicki, but sometimes it can trigger mutations that can lead to disease.

The noncoding RNA produced from transposons is thought to protect the genome by making sure that transposable elements are permanently turned off. But how are transposons selected for silencing in the first place? In a recent study, the research team found evidence that this noncoding RNA is produced throughout the entire genome, not just at or around transposons. Their results are published in the Proceedings of the National Academy of Sciences.

We are essentially proposing a new model. Our model says the entire genome is transcribed, and this pervasive transcription is functional, said Wierzbicki, also a member of the Center for RNA Biomedicine at U-M. This pervasive noncoding transcription acts as a surveillance system, catching and silencing new transposons as they appear. This speculative model will hopefully be able to be tested in more detail.

These results include two parts. First, the researchers had to determine that this noncoding RNA detected throughout the genome is real, not simply an error of detection methods. To do this, the researchers focused on an enzyme called an RNA polymerase. The role of RNA polymerases is to produce RNA using the sequence of DNA as a template, Wierzbicki said.

The researchers used a plant model called Arabidopsis thaliana, which has a specialized RNA polymerase dedicated to silencing transposons. The researchers could mutate this particular polymerase enzyme and create plants that were unable to produce an entire category of noncoding RNA. No other eukaryotic organism, including humans, would survive with an RNA polymerase mutated, which makes plants uniquely suited to studying the roles of noncoding RNA.

With the polymerase enzyme mutated, the researchers then compared the mutated plant to a wild-type planta plant that had not been altered. If they detected RNA in the wild-type plant but not in the mutant plant, they could confirm that the noncoding RNA was real. And they did.

Next, the researchers wanted to understand the role of this noncoding RNA. They expected to find that noncoding transcription was taking place on transposons, but nowhere else outside of the transposons. But what they found was that noncoding transcription was happening almost everywhere in the genome.

One of the researchers, Masayuki Tsuzuki, at the time a postdoctoral fellow in the Wierzbicki lab and now an assistant professor at the University of Tokyo, looked for this transcription by using high-throughput sequencing. This sequencing is an approach that produces a huge amount of data corresponding to noncoding transcription. In-depth analysis of these results allowed the group to prove where noncoding transcription is present.

They found evidence that noncoding RNA is produced across almost 50% of the plant genome, while transposons composed only 10%-20% of the genome. By comparing their data to previously published results they further found evidence that this noncoding RNA is needed for silencing of transposons that became reactivated.

So when the transposon is new, or it has been activated in a way that the cell forgot it was previously marked as a foreign object, how can it be recognized as being foreign? Wierzbicki said. Theres one common factor thats always needed, and thats this noncoding RNA that we are studying. No matter where the transposon was inserted in the gene, it could not be turned off if the noncoding RNA was not present.

Although the research team looked at Arabidopsis thaliana, a similar process may play out in other flowering plants as well as in fungi and animals. In fungi and animals, a similar process happens, except these two groups dont have the specialized RNA polymerase. Instead, they carry out a similar process using the same polymerase that contributes to protein production.

Wierzbicki and Tsuzukis fellow researchers include Shriya Sethuraman, a doctoral student in the Bioinformatics Graduate Program at Michigan Medicine; Adriana Coke, a research assistant in the U-M Department of Molecular, Cellular and Developmental Biology; M. Hafiz Rothi, a doctoral student in the U-M Department of Molecular, Cellular and Developmental Biology; and Alan Boyle, an associate professor of computational medicine and bioinformatics and of human genetics at Michigan Medicine.

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Researchers find that a type of RNA monitors the genome to help ensure its integrity - University of Michigan News

Africa is the cradle of humankind. All humans are descendants from this common pool of ancestors. Africa and its multitude of ethnolinguistic groups are therefore fundamental to learning more about humankind and our origins.

A human genome refers to the complete set of genetic information found in a human cell. We inherit our genomes from our parents. Studying the variations in different peoples genomes gives important clues to how genetic information influences peoples appearance and health. It can also tell us about our ancestry. To date, very few African individuals have been included in studies looking at genetic variation. Studying African genomes not only fills a gap in the current understanding of human genetic variation, but also reveals new insights into the history of African populations.

My colleagues and I, who are all members of the Human Heredity and Health (H3Africa) consortium, contributed to a landmark genetics study. This study focused on 426 individuals from 13 African countries. More than 50 different ethnolinguistic groups were represented in the study one of the most diverse groups of Africans ever to be included in such an investigation. We sequenced the whole genome of each of these individuals this means we could read every part of the genome to look for variation.

This study contributes a major, new source of African genomic data, which showcases the complex and vast diversity of African genetic variation. And it will support research for decades to come.

Our findings have broad relevance, from learning more about African history and migration, to clinical research into the impact of specific variants on health outcomes.

One of the key outcomes was the discovery of more than three million new genetic variants. This is significant because we are learning more about human genetic diversity in general, and discovering more differences that could be linked to disease or traits in the future.

This study also adds details to what is known about the migration and expansion of groups across the continent. We were able to show that Zambia was most probably an intermediate site on the likely route of migration from west Africa to east and south Africa. Evidence supporting movement from east Africa to central Nigeria between 1,500 and 2,000 years ago was also revealed, through the identification of a substantial amount of east African ancestry in a central Nigerian ethnolinguistic group, the Berom.

The study also enabled us to reclassify certain variants that were previously suspected to cause disease. Variants that cause serious genetic diseases are often rare in the general population, mostly because their effect is so severe that a person with such a variant often does not reach adulthood. But we observed many of these variants at quite common levels in the studied populations. One wouldnt expect that these types of disease-causing variants would be this common in healthy adults. This finding helps to reclassify these variants for clinical interpretation.

Finally, we found a surprising number of regions with signatures of natural selection that have not been previously reported. Selection means that when individuals are exposed to environmental factors like a viral infection, or a drastic new dietary component, some gene variants may confer an added adaptive advantage to the humans that bear them in their genome.

Our best interpretation of these findings is that as humans across Africa were exposed to different environments sometimes as a result of migration these variants were likely important to surviving in those new conditions. This has left an imprint on the genome and contributes to genomic diversity across the continent.

Our data has shown that we have not yet found all the variation in the human genome. There is more to learn by adding new, unstudied population groups. We know that less than a quarter of participants in genomics research are of non-European ancestry. Most available genetic data come from just three countries the UK (40%), the US (19%) and Iceland (12%).

It is essential to keep adding more genomic data from all global populations including Africa. This will ensure that everyone can benefit from the advances in health that precision medicine offers. Precision medicine refers to the customisation of healthcare to fit the individual. Including personal genetic information could radically change the nature and scope of healthcare options that would work best for that individual.

The Human Heredity and Health consortium is now in its eighth year of existence, and supports more than 51 diverse projects. These include studies focusing on diseases like diabetes, HIV and tuberculosis. The reference data generated through our study are already being put to use by many of the consortiums studies.

Read more: What we've learnt from building Africa's biggest genome library

Next, we are planning to take an even deeper look at the data to better understand what other types of genetic variation exist. We are also hoping to add further unstudied populations to grow and enrich this data set.

Building capacity for genomics research on the African continent is a key goal of Human Heredity and Health. An important aspect of this study is that it was driven and conducted by researchers and scientists from the African continent. Researchers from 24 institutions across Africa participated and led this investigation. This study showcases the availability of both infrastructure and skills for large-scale genomics research on the continent. It also highlights the prospect of future world-class research on this topic from Africa.

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Major new study unveils complexity and vast diversity of Africa's genetic variation - The Conversation CA

In the past few years, people have become fascinated with using their DNA to learn more about themselves, their origins, family trees, predisposition to health conditions and quirky traits. This has been enabled by the rise in popularity and the relative affordability of direct-to-consumer ancestry testing in places like the US. This testing allows people to swab their mouths to collect cells containing DNA, which are then sent off to companies for testing and analysis.

Today sites like AncestryDNA, 23andMe, MyHeritage and FTDNA dominate the European and US markets. But until recently, this service has been inaccessible to most South Africans. Thats because testing using overseas companies can be expensive, and there are logistical hurdles to shipping sample collection kits into and out of South Africa.

Recently, local companies like DNAnalysis and Be Happy To Be You have started to offer genetic testing, ranging from ancestry to nutrigenetics (what your genes say you should and should not eat) and health screenings.

Many potential clients are, however, sceptical about using these services. They view them as sub-standard and more expensive than some of the larger, overseas competitors. There are also concerns regarding privacy.

So, is supporting local businesses and getting your DNA analysed worth it? My opinion, as a human population geneticist who has researched the role that extensive genetic testing can play in mapping diseases, is yes. As more clients choose a local service provider for direct-to-consumer testing, the accuracy of the service will increase, the costs will decrease and the resulting data generation can be used to boost medical research efforts.

The process of completing a direct-to-consumer ancestry test is fairly simple. When you visit a site and request a test, you will be required to sign a consent form, fill in your personal information (contact details and address) and then wait for your test kit to be couriered to you. This kit is used to swab the inside of your mouth. The swabs are then sent back to the company for further processing, which involves extraction of your DNA and then computational analysis. An ancestry report is generated by comparing your genetic data to data of other worldwide populations.

But what of peoples concerns around accuracy, cost and privacy?

Firstly, there is no evidence that the services offered by local companies are sub-par. In fact, they should be more accurate because of the context in which the data is analysed. Local companies will have databases of South African data that other overseas companies do not. For example, instead of containing two different southern African populations (in line with overseas companies), local companies might have 10 and therefore be able to provide more detailed, granular reports.

Furthermore, scientists who work in local companies have acquired local knowledge and are therefore able to work with South Africas unique genetic diversity better than anyone else.

Secondly, testing in South Africa is for the most part not more expensive than overseas. If South Africans use an overseas company, theyll generally have to pay for courier fees to get a sample collection kit delivered and sent back to the company as well as potentially paying import taxes. Theres also a risk that the sample collection kit might get held up or even lost in either direction of the courier process. This may add to the overall cost.

Typically the price for direct-to-consumer ancestry testing in the US is between $69 and $99. Adding approximately R800 (around $50) for courier charges brings the cost for an international test to between R1,900 and R2,400, compared to between R1,000 and R2,499 locally (courier fees included). And, as more and more people start using local resources, the products and services will become cheaper over time.

Read more: What we've learnt from building Africa's biggest genome library

With regard to data privacy, confidentiality and anonymity, South Africa has some of the strictest laws that govern personal data, particularly the Protection of Personal Information Act. All local companies are required to adhere to this.

There is another aspect South Africans should consider when theyre thinking about using local services for genomic testing: the importance of creating a genomic citizenship movement.

When you send your DNA to a direct-to-consumer genetic testing company, you are investing in a product and service that benefits others. By making your de-identified genetic data available for use in local companies databases and for research purposes, you directly contribute to scientific development by increasing the accuracy of these services for other clients and in some cases, for yourself and for your family members.

Scientific researchers can use that de-identified data to investigate, for instance, why some individuals get sick and others dont. An example of this has been seen during the COVID-19 pandemic. Genetic data from direct-to-consumer genetic testing has been used to investigate how the disease progresses and why some patients are asymptomatic while others succumb to the disease. This was made possible by individuals who allowed researchers to use their genetic data for this purpose.

Over time, with an expansion of genetic data, it will be possible to diagnose patients with genetic diseases that would not have been diagnosed otherwise. Scientists will be able to answer questions regarding the efficacy of medications in some patients and speed up the development of gene therapies that could save countless lives.

The rise of direct-to-consumer services is an opportunity for South Africans to contribute, in their own way, to a greater genomic future.

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How South Africans can use their DNA to be good genomic citizens - The Conversation CA

COVID-19 Coronavirus molecule, March 24, 2020.

CDC | API | Gamma-Rapho via Getty Images

A team of CRISPR scientists at the New York Genome Center, New York University and Icahn School of Medicine at Mount Sinai said they have identified the genes that can protect human cells against Covid-19, a disease that has infected over 40 million and led to 1 million deaths worldwide.

The discovery comes after an eight-month screen of all 20,000 genes in the human genome led by Dr. Neville Sanjana at the New York Genome Center. Leading virologist at Mount Sinai, Dr. Benjamin tenOever, developed a series of human lung cell models for the coronavirus screening to better understand immune responses to the disease and co-authored the study.

Their study, published online last month by Cell, will appear in the scientific peer-reviewed journal's Jan. 7 print issue.

The goal was two-fold: to identify the genes that make human cells more resistant to SARS-CoV-2 virus; and test existing drugs on the market that may help stop the spread of the disease.

The breakthrough comes at a time when drug makers such as Pfizer, Oxford-AstraZeneca and Moderna are fast-forwarding vaccine and therapeutics to treat Covid-19. On Friday, Pfizer and BioNTech requested emergency authorization from the FDA for their Covid vaccine that contains genetic material called messenger RNA, which scientists expect provokes the immune system to fight the virus.

In order to better understand the complex relationships between host and virus genetic dependencies, the team used a broad range of analytical and experimental methods to validate their results. This integrative approach included genome editing, single-cell sequencing, confocal imaging and computational analyses of gene expression and proteomic datasets.

After intensive research, the scientists and doctors claim they have found 30 genes that block the virus from infecting human cells including RAB7A, a gene that seems to regulate the ACE-2 receptor that the virus binds to and uses to enter the cell. The spike protein's first contact with a human cell is through ACE-2 receptor.

"Our findings confirmed what scientists believe to be true about ACE-2 receptor's role in infection; it holds the key to unlocking the virus," said Dr. tenOever. "It also revealed the virus needs a toolbox of components to infect human cells. Everything must be in alignment for the virus to enter human cells."

The team discovered that the top-ranked genes those whose loss reduces viral infection substantially clustered into a handful of protein complexes, including vacuolar ATPases, Retromer, Commander, Arp2/3, and PI3K. Many of these protein complexes are involved in trafficking proteins to and from the cell membrane.

"We were very pleased to see multiple genes within the same family as top-ranked hits in our genome-wide screen. This gave us a high degree of confidence that these protein families were crucial to the virus lifecycle, either for getting into human cells or successful viral replication," said Dr. Zharko Daniloski, a postdoctoral fellow in the Sanjana Lab and co-first author of the study.

Using proteomic data, they found that several of the top-ranked host genes directly interact with the virus's own proteins, highlighting their central role in the viral lifecycle. The team also analyzed common host genes required for other viral pathogens, such as Zika or H1N1 pandemic influenza.

The research team also identified drugs that are currently on the market for different diseases that they claim block the entry of Covid-19 into human cells by increasing cellular cholesterol. In particular, they found three drugs currently on the market were more than 100-fold more effective in stopping viral entry in human lung cells:

The other five drugs that were tested called PIK-111, Compound 19, SAR 405, Autophinib, ALLN -- are used in research but are not yet branded and used in clinical trials for existing diseases.

Our findings confirmed what scientists believe to be true about ACE-2 receptor's role in infection; it holds the key to unlocking the virus.

Their findings offer insight into novel therapies that may be effective in treating Covid-19 and reveal the underlying molecular targets of those therapies.

The bioengineers in New York were working on other projects with gene-editing technology from CRISPR but quickly pivoted to studying the coronavirus when it swept through the metropolitan area last March. "Seeing the tragic impact of Covid-19 here in New York and across the world, we felt that we could use the high-throughput CRISPR gene editing tools that we have applied to other diseases to understand what are the key human genes required by the SARS-CoV-2 virus," said Dr. Sanjana.

Dr. Neville Sanjana and his team at the New York Genome Center used CRISPR to identify the genes that can protect human cells against Covid-19.

New York Genome Center

As he explained, "current treatments for SARS-CoV-2 infection currently go after the virus itself, but this study offers a better understanding of how host genes influence viral entry and will enable new avenues for therapeutic discovery."

Previously, Dr. Sanjana has applied genome-wide CRISPR screens to identify the genetic drivers of diverse diseases, including drug resistance in melanoma, immunotherapy failure, lung cancer metastasis, innate immunity, inborn metabolic disorders and muscular dystrophy.

"The hope is that the data from this study which pinpoints required genes for SARS-CoV-2 infection could in the future work be combined with human genome sequencing data to identify individuals that might be either more susceptible or more resistant to Covid-19," Dr. Sanjana said.

The New York team is not the first to use CRISPR gene editing techniques to fight Covid-19. Other bioengineering groups at MIT and Stanford have been using CRISPR to develop ways to fight the SARS-CoV-2 and develop diagnostic tools for Covid-19.

The potential for using CRISPR to eliminate viruses has already generated some enthusiasm in the research community. Last year, for example, Excision BioTherapeuticslicenseda technology from Temple University that uses CRISPR, combined with antiretroviral therapy, to eliminate HIV, the virus that causes AIDS.

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Gene experts claim they identified human genes that can protect against Covid-19 - CNBC

In 2003, biologists created the first ever human genome sequence. The 3 billion DNA letter sequence, called the reference genome, was mostly made up of DNA donated from people in the city of Buffalo, New York. So far, when clinicians and researchers study an individuals genome, they compare it to the reference genome to identify differences. But can you compare all of humanity to one genome? No, because one reference genome does not convey the genomic diversity of the human species. We need many reference genomes a pangenome. This monumental undertaking is already taking place and is poised to redefine the future of genomic research and human health.

This video was co-produced by Massive Science and NIH/NHGRI.

Presented by the National Human Genome Research InstituteDirection and animation by Rosanna WanNarration by Dr Shawntel OkonkwoSound + music by SkillbardScript by Harriet Bailey and Prabarna GangulyProducer Harriet BaileySenior producer Nadja OerteltExecutive producer Prabarna GangulyProduced for and supported by the National Human Genome Research Institute

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Video: The Ambitious Project To Prepare a Library of Genomes of the Human Species - The Wire Science