Category Archives: Human Genetics

Many human diseases can differ between males and females in their prevalence, manifestation, severity or age of onset. Examples include Lupus, where more than 80% of patients are females; Alzheimers disease, where females have higher incidence and tend to suffer quicker cognitive decline; and COVID-19 infections that are frequently more severe in males.

These sex differences may have a genetic basis that is attributable to the sex chromosomes. The X chromosome one of the two sex chromosomes is known to play an important role in human development and disease. New research led by Penn State College of Medicine reveals for the first time that sex-biased diseases can be attributable to genes that escape X chromosome inactivation (XCI), a process that ensures that females do not overexpress genes on their X-chromosomes.

The team developed a genetic tool that can identify these XCI escape genes, and it may also help in determining whether a female will develop a sex-biased disease and if the disease will become progressively worse over time. The tool may even be useful in understanding the sex differences in immune responses to COVID-19, as the disease is thought to produce more severe symptoms and higher mortality in men than in women.

The X chromosome plays an important role in human development and disease, yet the X chromosome is frequently ignored in human genetic studies because of bioinformatics challenges in the analysis of the data, said Laura Carrel, associate professor of biochemistry and molecular biology, Penn State College of Medicine. Our new method gets around these challenges and allows us to identify XCI escape genes and assess their role in sex-biased diseases. With further research and fine-tuning, we think it could serve as a predictive tool in these disorders and could lead to the identification of new disease treatments and interventions.

The human genome is organized into 23 pairs of chromosomes, one pair of which is the sex chromosomes. This pair comprises two X chromosomes for females and one X and one Y chromosome for males. Early in embryonic development in females, one of the two X chromosomes is randomly inactivated to ensure that, like in males, only one functional copy of the X chromosome either the one inherited from the females mother or the one inherited from her father occurs in each cell.

In females, about 30% of the genes on the X chromosome escape this inactivation or XCI leaving them with two functional copies of those genes, said Carrel. The question is, does having two copies of those genes make a female more susceptible to traits, such as lupus, that show a sex bias?

To answer this question, a critical first step is to identify the XCI escape genes. Yet, conducting a chromosome-wide analysis is difficult due to the random nature of XCI in early development, as XCI affects the X chromosome that a female inherits from one parent in some cells, but the other X in other cells.

In theirstudy, which published on Aug. 23 in the journal Genome Research, the researchers developed a novel statistical model, called XCIR (X-Chromosome Inactivation for RNA-seq), that can identify XCI escape genes using bulk RNA-sequencing data, a type of genetic data. The method separately evaluates how much a gene is expressed from each X chromosome. A gene is deemed to escape XCI if the ratio of its expression from the two X chromosomes differs significantly from genes that are known to be X inactivated. The method outperforms other approaches because it can more effectively handle the errors arising from next-generation sequencing technologies and the complex biology of XCI.

Our method available in an intuitive, well-documented and freely available software is more powerful than alternative approaches and is computationally efficient to handle large population-scale datasets, said Dajiang Liu, associate professor of public health sciences and biochemistry and molecular biology, Penn State College of Medicine.

The team applied its method to a dataset including nearly half a million people, and identified hundreds of traits, including male- or female-biased diseases such as lupus, that may be influenced by these genes that escape XCI. As shown by others, the escape genes also contribute to Alzheimers disease and response to COVID-19 infections as well.

We have developed the methodology needed to establish XCI status for population-sized datasets, said Liu. This work highlights the increased importance of XCI escape genes to female-biased diseases and may one day be used to accurately predict disease. Importantly, a better understanding of the sex chromosomes will be an important step in resolving health disparities between the sexes.

Reference: Sauteraud R, Stahl J, James J, et al. 2021. Inferring genes that escape X-Chromosome inactivation reveals important contribution of variable escape genes to sex-biased diseases. Genome Research.doi: 10.1101/gr.275677.121.

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

Go here to read the rest:
Exploring the Genetics of Sex-Biased Diseases, Including Lupus - Technology Networks

Scientistsat the University of Toronto's Donnelly Centre for Cellular and Biomedical Researchhave received $1.9 million to shed light on how variation in our genomes affects disease risk and severity in a bid to improve interpretation of personal genome information.

A joint study by teams in Toronto and Boston will investigate how variation at the DNA level affects the function of encoded proteins. Associate ProfessorMikko Taipaleand ProfessorFrederick Roth, both principal investigators at the Donnelly Centrein the Temerty Faculty of Medicine, are leading the effort at U of T. They are working with Anne Carpenter, ofthe Broad Institute of Massachusetts Institute of Technology and Harvard, and Marc Vidal, a Harvard University genetics professor, director of the project and director of the Center for Cancer Systems Biologyat Dana-Farber Cancer Institute.

The research is part of a newmultimillion-dollar initiative in the U.S., theImpact of Genomic Variation on Function Consortium, which brings together scientists and clinicians from all over the world to advance an understanding of genome function. The total funding awarded for the project is US$8.3 million,or roughly$10.5 million.

Over the next five years, the researchers will develop a catalog of experimental data to assist in the classification of missense variants alterations in the DNA code which change the amino-acid composition of the encoded protein as either pathogenic and capable of causing disease, or benign and harmless.

For the majority of missense variants, their impact on health remains unknown which is why they are called variants of unknown significance, or VUS. A genetic test with a VUS result can be agonizing for patients as it leaves them in the darkabout its meaning.

When people get a genetic diagnostic test and find a variant in their gene, a genetic counselor has to interpret it and a VUS result is essentially throwing up their hands and saying we dont know, says Roth, who is also a professor of molecular genetics and computer science at U of T and a senior investigator at the Lunenfeld-Tanenbaum Research Institute at Sinai Health.

The promise of personalized medicine based on your personal genome sequence comes to a grinding halt when the majority of the variants that are found cant be interpreted, he says.

Overall, the researchers will investigate around 75,000 variants in about 1,000 genes with known links to genetic disorders, such as cystic fibrosis and Duchenne muscular dystrophy, for which dozens of variants have already been documented across patient populations. This is key because sufficient numbers of known pathogenic and benign variants are required for VUSs to be compared to and classified accordingly.

For each gene, the researchers will use several lab tests to compare how dozens of its encoded protein variants, perform at the cellular level. The work will reveal mechanistic insight into variant protein function in health and how it goes awry in disease. It will also enable the classification of VUSs by comparing them to their benign and pathogenic counterparts.

Roths team is tasked with helping to construct the DNA clones allowing variant proteins to be produced. Each variant will be fluorescently tagged to make it visible so that its abundance and cellular localization can be determined by Taipales team using automated high-content microscopy.

We will see whether proteins abundances change and whether they end up where they are supposed to be or in a new location, as well as whether they have an effect on cell morphology, says Taipale, a faculty member in the department of molecular genetics and a Canada Research Chair in Functional Proteomics and Proteostasis.

With microscopy you can get so much data including also how variants affect the different compartments inside the cell and cellular fitness overall, Taipale says. Image data analysis will be carried out using computer vision algorithms developed by Carpenters team at the Broad.

Meanwhile, Vidals lab at the Dana-Farber Cancer Institute will assess each variants ability to interact with other cellular proteins.

The study will identify which tests are best suited for different types of proteins to provide a much-needed framework for future variant classification on a genome-wide scale where its potential impact on health is both vast and unexplored.

Roth co-founded theAtlas of Variant Effects Alliance, an international consortium with the aim of testing the functional impact of all possible variants in human genes even before they have been discovered by genome sequencing.

We want to test every possible variant even though weve never seen it in the human before so that when we do see it, were ready, says Roth. The goal is to build a look-up table of variant effects in advance of ever seeing it in the human and have a sense of their functional impacts.

See the rest here:
U of T researchers to study effects of genetic variation on health - News@UofT

After 90years of taxonomic uncertainties, using phenotypic, phylogenetic, and population genetics analyses, the two uncultivated fungi causing skin disease in humans and dolphins, long known as Lacazia loboi8, are now placed as separate species within the genus Paracoccidioides. Early studies using phenotypic or phylogenetic data alone erroneously placed these two fungal pathogens in different genera and species3,4,5,6,7,8,12,13,15,16,17,24,25. This trend persisted for years2,13,16,17,25. For instance, recent studies using several partial DNA sequences recovered from Brazilian humans with skin disease in phylogenetic analyses concluded that the genus Lacazia, the accepted name at that time, was an independent taxon from Paracoccidioides species16,24,25. Their phylogenetic data was correct, but their analyses missed the inclusion of DNA from the uncultivated pathogen causing skin disease in dolphins. This was an understandable mistake, since the collection and processing specimens from infected dolphins is highly regulated and the fact that the etiology of dolphins disease was long believed to be the same as that in humans, as shown in Fig.1 and Table 1. Although P. cetii has numerous phenotypic differences with Paracoccidioides species (Table 1, Fig.1), in the pass used to group them in separated clusters2,3,7,8, our data showed they share several phylogenetic features in common (Figs. 4, 5 and 6). With the addition of P. cetii DNA sequences, the phylogenetic support of closely related Paracoccidioides species dramatically changed. For example, P. loboi clustered in a monophyletic group sister to P. lutzii, even with the inclusion of homologous dimorphic Onygenales DNA sequences as outgroup (Figs.4b, 5), whereas the support of monophyletic species within the genus weakened (Figs. 4, 5 and 6). More dolphin DNA sequences from different geographical locations must be sequenced to understand P. cetiis true evolutionary traits.

Several studies reported geographical cryptic speciation among Paracoccidioides species14,24,26,27,28. In those analyses the presence of at least five species within the genus, including P. lutzii, was found14,15,24,27,29,30. Recent genome sequencing in phylogenetic analysis tend to validate these findings26,28,29. Although the DNA sequences of P. loboi were used in some of the analyses, the human skin pathogen was always placed as an independent genus from that in Paracoccidioides species16,24,25. The placement of P. cetii sister to P. americana DNA sequences in this study, indicates the use of phenotypic or phylogenetic characteristics without the inclusion of anomalous species, can lead to inaccuracies in the taxonomic and phylogenetic classification of these type of microbes. For instance, our data, using several statistical tools, consistently showed the presence of different clusters within Paracoccidioides species. In our analyses, P. americana, P. cetii, P. lutzii, and P. loboi were placed in monophyletic groups sister to the remaining Paracoccidioides species (Figs. 2, 3, 4, 5 and 6). Therefore, the addition of P. cetii to the genus Paracoccidioides not only confirmed that the genus has indeed a high level of speciation but, indicates that the concept of species delimitation in this genus must be revisited12,31.

Recently, Vilela et al.16, using phylogenetic analysis of five different genes, showed P. loboi shared the same ancestor with Paracoccidioides species. The results in our study support their proposal. The main obstacle of this hypothesis at that time was the phenotypic features of P. loboi (Fig.1). However, if P. loboi and P. cetii (both uncultivated and subcutaneous pathogens) share the same ancestor with other Paracoccidioides species (cultivated and causing systemic infections), the likelihood that the ancestor of Paracoccidioides species could growth in culture, as previously suggested, is a strong possibility16. If this concept is correct, when in the evolutionary history of P. cetii and P. loboi they lost the capacity to grow in culture? What evolutionary pressure triggered such a change? Sadly, as is common in neglected pathogens such as P. cetii and P. loboi key questions such as these, remain without an answer. Interestingly, the uncultivated feature found in these two neglected fungi was also reported in a strain of Histoplasma capsulatum infecting monkeys, suggesting that an uncultivated ancestral trait in the Onygenales dimorphic fungi may be at work32. However, the evolutionary pressures that triggered such ancestral feature remains an enigma.

The report of new human cases of paracoccidioidomycosis loboi acquired by traveling to endemic areas2,3,4,5,33,34,35,36, suggests P. loboi may has a similar phenotype (hyphae with conidia) to the one displayed by Paracoccidioides species in nature and in culture. Thus, it may be present in specific ecological niches in the endemic areas (around the Amazon basin and other Latin American big rivers)2,14,15,25. Therefore, it is possible P. cetii and P. loboi may have a phenotype in nature similar to that of Paracoccidioides species (hyphae with conidia). Under this scenario, both uncultivated pathogens display a mycelia form with conidia and the classic life cycle style of dimorphic fungi in nature25. As is the case in other dimorphic fungi, these propagules could then contact susceptible hosts (human, dolphins) switching from hyphaeyeast thus, causing subcutaneous infections. Perhaps due to abnormalities on the molecular mechanisms of yeasthyphae conversion (mutations?), once the hyphaeyeast conversion occurs, it cannot longer switch back from yeast to hyphal phase. However, the yeast phase of both pathogens can infect other hosts, as had been demonstrated in accidental and experimental infection with yeast-like cells from infected humans and dolphins2,37,38,39,40,41,42. Despite attempts made by the Broad Institute (https://www.broadinstitute.org/fungal-genome-initiative/lacazia-loboi-sequencing), only fragmented genomic information is available for P. loboi, and the genome of P. cetii is yet to be sequence. We hypothesize that the genomes of both uncultivated pathogens may hide important genomic clues that could answer this and other evolutionary questions.

Several P. cetii DNA sequences recovered from dolphins captured in Brazil, Cuba, Japan, and the USA are currently available in the database (Table S1)19,20,21,22,23. The complete ITS DNA sequences from Brazilian and Cuban dolphins with paracoccidioidomycosis ceti, showed high percentage of identify with the DNA sequences in this study (ITS=100%) whereas the partial Gp43 DNA sequences from a Japanese dolphin (471bp) had 98.62% identity with P. cetii DNA sequences from dolphins captured in the Americas. During Gp43 DNA alignment of Japanese and USA dolphins, a five nucleotides gap was consistently present in the DNA sequences of USA dolphins. Moreover, two additional 266bp GP43 DNA sequences extracted from a Japanese dolphin (Lagenorhynhus obliquidens) with paracoccidioidomycosis ceti showing, 99.62% identity with P. brasiliensis (sensu lato). In our analyses, these two sequences (only 110bp could be used) clustered also with P. brasiliensis (Fig.4, red rectangle). However, the same DNA sequences clustered close to P. cetii in haplotype analysis indicating a fragile relationship (Fig.3). If P. cetii DNA sequences from Japanese dolphins are accurate, the differences in the genetic makeup of these two populations of uncultivated pathogens is intriguing and deserve further analysis. Our data suggest P. cetii strains causing paracoccidioidomycosis ceti in Japanese and USA dolphins, likely are evolving into two different populations.

According to Teixeira et al.24, the estimated time for genetic divergence in Paracoccidioides species was calculated around 33 million years. Although, others have questioned this result31, Carruthers et al.43, cautioned that the use of linage-specific data usually demonstrate approximate divergence time regardless of the number of loci interrogated. Nonetheless, according to these reports, Paracoccidioides species probably diverged from their ancestor from a fraction of a million of years (P. restrepiensis and P. venezuelensis) to 1030 million of years (P. lutzii and P. brasiliensis, sensu lato)24,31. Conversely, dolphins evolved into aquatic mammals~50 to 30 million years ago, around late Paleocene period (Eocene, Oligocene epochs)44. According to fossil records, South America at this time had a large body of water crossing from the north Atlantic Ocean to what is today Bolivia, Brazil, Ecuador, Colombia, Peru and Venezuela45, all endemic areas of these species3,4,5,24,26,29, that lasted for millions of years. A similar situation occurred in what is today the estuary of the Amazon River. The current location of Paracoccidioides species (including P. loboi), coincide with the locations of such geological periods, and then it is quite possible that during the time following these geological events, an ancestor of P. cetii first encountered dolphins entering these areas. Since humans came to South Americas only~15,000-year ago46, likely the ancestor of Paracoccidioides species infected dolphin first and later humans. Whether this event had a role on the pathogenic capabilities of the genus to infect mammals is difficult to determine, nonetheless it is an intriguing possibility.

Working with uncultivated pathogens infecting the skin of mammals is challenging. Not only because collecting specimens from these species (dolphins are protected species and human cases are located in poor remote rural areas) is extremely difficult, but because open lesions usually harbor numerous environmental contaminants, which in the past had led to erroneous conclusions on the classifications of these two anomalous pathogens2,8,15,16,25,47. Furthermore, these unusual fungi are not in the list of neglected pathogens, thus discouraging investigators to submit proposals to funding organizations. Previous studies using P. loboi in phenotypic or phylogenetic analyses placed this anomalous pathogen away from the genus Paracoccidioides2,4,15,16,25. This study found that the use of phenotypic or phylogenetic approaches without the inclusion of DNA from infected dolphins, likely led previous studies to flawed data15,16,25. Thus, the failure of including organisms sharing a common ancestor, based in phenotypic or phylogenetic traits alone, could result in incomplete or incorrect assessment of the investigated populations. This study showed that the interpretation of taxonomic and/or phylogenetic data could be affected by missing neighboring anomalous taxa.

Go here to read the rest:
The taxonomy of two uncultivated fungal mammalian pathogens is revealed through phylogeny and population genetic analyses | Scientific Reports -...

THOUSAND OAKS, Calif., Sept. 14, 2021 /PRNewswire/ -- Amgen(NASDAQ: AMGN) and The Lundquist Institute today announced that Diadem Biotherapeutics, Inc., has been awarded the first Amgen Golden Ticket in Southern California. Diadem will receive one year of lab space at BioLabs LA at The Lundquist Institute (TLI) as well as additional facility benefits and connections to Amgen's scientific and business leaders.

The 2021 Amgen Golden Ticket winner was chosen by an internal team of Amgen scientific leaders at a virtual pitch event. Five finalists pitched their business plans before Amgen's internal committee that evaluated the strength and novelty of their scientific rationale, subject matter expertise and business plan viability.This is the first of three Amgen Golden Tickets to be awarded over the next three years to help accelerate life science start-ups in Southern California.

Perspectives on announcement:

Amgen supports life science start-ups through Golden Ticket awards and affiliated engagement in other Biotech Innovative hubs, including San Francisco, Boston and Toronto.

About Diadem Biotherapeutics, Inc.Diadem Biotherapeutics, Inc.is a platform therapeutics company developing a broad pipeline of first-in-class immunotherapies. Leveraging expertise in genetic engineering and scalable bioprocessing, Diadem is developing cell secreted nanovesicles precisely engineered to deliver signals that mimic natural cell-to-cell signaling. Diadem's unique approach enables precise modulation of targets that play a role inchronic inflammation, autoimmune diseases and immune control of cancers, addressing some critical unmet clinical needs. For more information, visit http://www.diadembio.com.

About AmgenAmgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology.

Amgen focuses on areas of high unmet medical need and leverages its expertise to strive for solutions that improve health outcomes and dramatically improve people's lives. A biotechnology pioneer since 1980, Amgen has grown to be one of the world's leading independent biotechnology companies, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential.For more information, visit http://www.amgen.com and follow us on http://www.twitter.com/amgen.

About The Lundquist Institute: Research with reach The Lundquist Institute is an engine of innovation with a global reach and a 69-year reputation of improving and saving lives. With its new medical research building, its state-of-the-art incubator, "BioLabs at The Lundquist," existing laboratory and support infrastructure, and the development of a new 15-acre businesstech park, the Lundquist Institute serves as a hub for the Los Angeles area's burgeoning biotech scene. The research institute has over 100 principal investigators (Ph.D.s, M.D.s, and M.D./Ph.D.s) working on more than 600 research studies, including therapies for numerous, and often fatal orphan diseases. Find out more at https://lundquist.org.

About BioLabs LA at The Lundquist InstituteEncompassing the entire third floor of The Lundquist Institute's new Medical Research Lab building, BioLabs LA offers shared lab facilities designed for high-potential, early-stage life since companies. BioLabs creates co-working communities that pair premium, fully equipped and supported lab and office space with unparalleled access for entrepreneurs to networking, industry partners, and capital.Find out more athttps://www.biolabs.io/la.

CONTACT:

AmgenMichael Strapazon, 805-313-5553 (media)

The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical CenterKeith B. Hoffman, Ph.D., (310) 974-9301, [emailprotected]

BioLabs LALindsay Bourgeois, (978) 852-1081, [emailprotected]

SOURCE Amgen

http://www.amgen.com

Read more here:
Amgen And The Lundquist Institute Announce That Diadem Therapeuctics Will Receive The First Amgen Golden Ticket To BioLabs LA - PRNewswire

THOUSAND OAKS, Calif., Sept. 13, 2021 /PRNewswire/ -- Amgen (NASDAQ:AMGN) will host a webcast call for the investment community in conjunction with the European Society for Medical Oncology (ESMO) 2021 Congress. OnThursday, Sept. 16, 2021, at8:30 a.m. ET, David M. Reese, M.D., executive vice president of Research and Development atAmgen, along with other members ofAmgen's management team, will discuss clinical data being presented on the Company's KRASG12C inhibitor LUMAKRAS (sotorasib) in combination with Vectibix (panitumumab).

Live audio of the investor call will be broadcast over the internet simultaneously and will be available to members of the news media, investors and the general public.

The webcast, as with other selected presentations regarding developments in Amgen's business given at certain investor and medical conferences, can be accessed on Amgen's website, http://www.amgen.com, under Investors. Information regarding presentation times, webcast availability and webcast links are noted on Amgen's Investor Relations Events Calendar. The webcast will be archived and available for replay for at least 90 days after the event.

About Amgen Amgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology.

Amgen focuses on areas of high unmet medical need and leverages its expertise to strive for solutions that improve health outcomes and dramatically improve people's lives. A biotechnology pioneer since 1980, Amgen has grown to be one of the world's leading independent biotechnology companies, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential.

For more information, visitwww.amgen.comand follow us onwww.twitter.com/amgen.

CONTACT: Amgen, Thousand Oaks Megan Fox, 805-447-1423 (media) Trish Rowland, 805-447-5631(media) Arvind Sood, 805-447-1060 (investors)

SOURCE Amgen

http://www.amgen.com

Originally posted here:
Amgen To Webcast Investor Call At ESMO 2021 - PRNewswire

Novel drug-development approach combines advanced insights into critical neuronal cell pathways with cutting-edge assays to enable next-generation therapies

Lead program targets Parkinsons disease and all forms of Gaucher disease

CHICAGO, Sept. 14, 2021 (News) Vanqua Bio, a Chicago-based biopharmaceutical company dedicated to discovering and developing next-generation medicines for neurodegenerative diseases, today announced that it closed an $85 million Series B financing round, led by Omega Funds. The syndicate includes Series A investor OrbiMed and new investors Omega Funds, Surveyor Capital (a Citadel company), Avoro Ventures, Casdin Capital, Pontifax, Eli Lilly and Company, Logos Capital, and Osage University Partners. Proceeds from the financing will be used to accelerate the development of the companys innovative therapeutic programs. The need for effective neurodegenerative therapies is urgent; every day, the lives of thousands of people are changed forever following a diagnosis of Parkinsons disease (PD), Gaucher disease (GD), Alzheimers disease (AD), or amyotrophic lateral sclerosis (ALS).

Vanqua Bio is helping usher in a new era of hope for people living with neurodegenerative disorders. Our mission to develop effective therapies that slow or stop the progression of PD, AD, ALS, and Gaucher disease is a very personal one, and we are excited to have the support of world-class investors, said Jim Sullivan, PhD, Co-founder and Chief Executive Officer of Vanqua Bio. We are a patient-founded company with a technology platform based on seminal research conducted by Dimitri Krainc, MD, PhD, Chair of the Department of Neurology at Northwestern Universitys Feinberg School of Medicine, that is allowing us to identify a new generation of therapeutics with transformative potential. (Click to Tweet.)

Vanqua Bios drug development approach overcomes longstanding challenges in the neuroscience field by capitalizing on the power of human genetics to identify genes that cause or increase the risk of neurodegenerative disease. The company leverages novel, proprietary research tools and in vitro modeling of disease based on patient-derived neuronal cells to translate these genetic insights into transformative therapies.

We are delighted to have successfully led this financing for Vanqua Bio, and to partner with Jim and his team and the companys strong syndicate of dedicated, long-term investors, said Bernard Davitian, Partner at Omega Funds. Omega believes Vanqua Bios accomplished management team is well positioned to deliver on the immense potential of the companys precision medicine approach to neurodegeneration.

Targeting GCase Activation

The companys lead program is focused on developing small-molecule activators of glucocerebrosidase (GCase), an enzyme that regulates lipid homeostasis in cells. Reductions in the activity of GCase disrupt the function of the lysosome, the recycling center of the cell, enabling toxic forms of proteins, including alpha synuclein, to accumulate and harm neurons. Alpha synuclein aggregation is a hallmark of multiple neurodegenerative diseases including PD. Mutations in the gene that encodes GCase (GBA1) can cause GD and are strongly associated with a form of Parkinsons disease called GBA-PD and a subset of Lewy body dementia (GBA-LBD) cases. Vanqua Bios Series B financing will advance the companys best-in-class GCase activators into human testing within the next two years, initially focusing on GD and GBA-PD.

Of the eight million Parkinsons patients around the world, up to 800,000 have GBA-PD. These individuals urgently need targeted therapies that can improve their outcomes, said Jonathan Silverstein, J.D., a member of Vanqua Bios Board of Directors, Executive Partner at OrbiMed, and founder of the Silverstein Foundation for Parkinsons with GBA. Vanqua Bios unique approach to discovering novel GCase activators holds great promise in enabling new targeted therapies for GBA-PD patients. I have confidence in the companys potential to impact patients lives, dramatically improve the discovery and development process for additional neurodegenerative disease therapies, and create value for investors.

In addition to its GCase activator programs, Vanqua Bio will also advance programs targeting the innate immune system, which, when overactivated, can accelerate the progression of several neurological diseases. The company is advancing small molecule and antisense oligonucleotide programs with an initial focus on ALS and AD.

Proven Leadership Team

Vanqua Bios leadership team brings a track record of discovering and developing cutting-edge, commercially successful therapeutics. Previously Vice President of Research at AbbVie, Dr. Sullivan helped discover multiple therapies, including RINVOQ, VENCLEXTAand MAVYRET, which have transformed the treatment of rheumatoid arthritis, certain blood cancers, and hepatitis C, respectively. Kevin Hunt, PhD, Vanqua Bios Chief Scientific Officer, previously served as Executive Director of Drug Discovery for Edgewise Therapeutics, overseeing both internal and external preclinical drug discovery and development. Dr. Hunt also discovered multiple clinical candidates for severe diseases and held prior roles at Array Biopharma, Calico Life Sciences, and the University of Texas Southwestern Medical Center. Co-Founder Dr. Dimitri Krainc, a leading expert on uncovering molecular pathways that contribute to neurodegenerative diseases, chairs Vanqua Bios Scientific Advisory Board.

Mr. Davitian and Sara Nayeem, MD (Avoro Ventures), are joining Vanqua Bios Board of Directors, which includes Dr. Sullivan, Mr. Silverstein (OrbiMed), Mona Ashiya, PhD (OrbiMed), and Stephen Squinto, PhD (OrbiMed).

Given the strong genetic validation for GCase as a target for GBA Parkinsons and Gaucherpatients, the high unmet need inthese populations, and the expertise of the Vanqua Bio team in developing small molecule drugs, we are very enthusiastic about Vanquas strategy, said Dr. Nayeem of Avoro Ventures. The company also benefits from an impressive and deeply knowledgeable board of directors, which Avoro Ventures is honored to join.

About Vanqua Bio

Founded in 2019 and headquartered in Chicago near Northwestern Universitys world-renowned Krainc Laboratory, Vanqua Bio is a biopharmaceutical company dedicated to discovering and developing next-generation medicines that have the potential to transform the lives of patients with neurodegenerative diseases. Our technology platform utilizes human genetics and patient-derived neuronal cells to identify, validate, and clinically translate novel disease pathways associated with lysosomal dysfunction or aberrant activation of the innate immune system. Our lead program targets glucocerebrosidase (GCase) as a potential treatment for Parkinsons disease (PD) and all forms of Gaucher disease. Additional programs address overactivation of the innate immune system in central and peripheral neurodegenerative disorders, including ALS and Alzheimers disease. For more information, go to http://www.vanquabio.com.

Media Contact

Erich SandovalLazar-FINN PartnersErich.sandoval@finnpartners.com(917) 497-2867

Follow this link:
Vanqua Bio Launches with $85 Million Series B Financing and - Health Bollyinside - BollyInside

Comparing Human Genetic Similarity to Other Life Forms

Of the three billion genetic building blocks that make us living things, only a handful are uniquely ours. In fact, despite our differences on the outside, humans are 99.9% genetically similar to one another.

But how alike are we to other, non-human life forms? Turns out, were a lot more similar than you might think.

First, how do scientists compare the genetic makeup of various life forms?

Comparative genomics is a branch of biology that compares genome sequences across different species to identify their similarities and differences.

This field of research is important because it:

According to the National Human Genome Research Institute (NHGRI), scientists have already sequenced the genomes of more than 250 animal species, as well as 50 bird species.

Perhaps unsurprisingly, chimps are one of our closest genetic relatives in the animal kingdom.

Because of our similarities, chimpanzees have a similar immune system to humans, which means theyre susceptible to viruses such as AIDS and hepatitis.

Though chimps are one of our closest relatives, other species are strongly linked to humans as welland not necessarily the ones youd think.

For instance, according to NHGRI, fruit flies are 60% genetically similar to humans.

This may sound confusing at first, since humans and insects couldnt be more physically different. However, because we share many of the same essential needs to sustain life, such as the need for oxygen, these similarities are reflected in our genetics.

Its important to note that being genetically similar to something is different than sharing the same DNA. Thats because genes (the part of DNA responsible for making protein) only account for up to 2% of your DNA, while the rest of your genome is made up of what scientists call non-coding DNA.

So while a banana is 60% genetically similar to humans, only 1.2% of our DNA is shared.

Like this? Then check out this article on Earths Biomass

See original here:
Visualizing the Typical Atlantic Hurricane Season - Visual Capitalist

The information in genomes provides the instruction set for producing each living organism on the planet. While we have a growing understanding of the basic biochemical functions of many of the individual genes in genomes, understanding the complex processes by which this encoded information is read out to orchestrate production of incredibly diverse cell types and organ functions, and how different species use strikingly similar gene sets to nonetheless produce fantastically diverse organismal morphologies with distinct survival and reproductive strategies, comprise many of the deepest questions in all of science. Moreover, we recognize that inherited or acquired variation in DNA sequence and changes in epigenetic states contribute to the causation of virtually every disease that afflicts our species. Spectacular advances in genetic and genomic analysis now provide the tools to answer these fundamental questions.

Members of the Department of Genetics conduct basic research using genetics and genomics of model organisms (yeast, fruit fly, worm, zebrafish, mouse) and humans to understand fundamental mechanisms of biology and disease. Areas of active investigation include genetic and epigenetic regulation of development, molecular genetics, genomics and cell biology of stem cells, the biochemistry of micro RNA production and their regulation of gene expression, and genetic and genomic analysis of diseases in model systems and humans including cancer, cardiovascular and kidney disease, neurodegeneration and regeneration, and neuropsychiatric disease. Members of the Department have also been at the forefront of technology development in the use of new methods for genetic analysis, including new methods for engineering mutations as well as new methods for production and analysis of large genomic data sets.

The Department sponsors a graduate program leading to the PhD in the areas of molecular genetics and genomics, development, and stem cell biology. Admission to the Graduate Program is through the Combined Programs in Biological and Biomedical Sciences (BBS).

In addition to these basic science efforts, the Department is also responsible for providing clinical care in Medical Genetics in the Yale New Haven Health System. Clinical genetics services include inpatient consultation and care, general, subspecialty, and prenatal genetics clinics, and clinical laboratories for cytogenetics, DNA diagnostics, and biochemical diagnostics. The Department sponsors a Medical Genetics Residency program leading to certification by the American Board of Medical Genetics. Admission to the Genetics Residency is directly through the Department.

The rest is here:
Genetics < Genetics - Yale School of Medicine

Compliments of Scribble

The sequencing of the human genome in 2000 gave rise to the vision ofpersonalized medicine. Realizing the importance of this landmark achievement, Clemson University established Human Genetics as a major pillar of its long-term strategicScienceForwardplan. This vision was realized in 2016 with philanthropic support of Self Regional Healthcare and the Self Family Foundation, leading to the construction of Self Regional Hall on the Partnership Innovation campus of theGreenwood Genetic Center(GGC).

Self Regional Hall is a 17,000 sq. ft. state-of-the-art facility designed to provide acollaborative environmentthat is conducive to spontaneousinteractions among students and faculty. TheClemson Center for Human Geneticswas formally inaugurated in the facility on August 8, 2018.

In the short period of three years, the Center for Human Genetics has flourished under the leadership of its inaugural director,Dr. Trudy Mackay.

The Center started with two faculty Dr. Mackay and spouse and long-term collaborator, Dr. Robert Anholt two staff scientists, and two doctoral students. With strong support from Clemson University, the Center recruited four assistant professors from Yale University, Stanford University, the University of Chicago, and the University of North Carolina at Chapel Hill. This enabled the Center to expand rapidly to six faculty and a cohort of 16 graduate students on the Greenwood campus and eight affiliated members on the main campus of Clemson University.

In 2021, the Clemson University Center for Human Genetics, in collaboration with the GGC, received a grant from the National Institutes of Health for over $13.5 million total cost to establish a Center of Biomedical Research Excellence (COBRE) in Human Genetics to promote the professional development of young investigators.

The goals of the Clemson Center are two-fold:

1. to leverage comprehensivesystems genetic approaches andcomparative genomics to elucidate fundamental principles of the genetic underpinnings of human complex traits, including disease risk.

2. to promote precision medicine by developing advanced mathematical models to predict disease risk and assess therapeutic benefits based on genetic and environmental factors.

To enable these activities, the Center has established the most advanced genomics facility in South Carolina with capabilities for short- and long-read DNA sequencing as well as analyses of gene expression networks in single cells. The Center also contains a microscopy facility, a bioinformatics facility, and its own high performance computing cluster for analyses of large datasets.

Faculty in the Center use comparative genomics approaches to gain insights in human disorders. Such approaches include studies on the fruitfly (Drosophila) model, which enables sophisticated genetic experimentation, zebrafish (in collaboration with the GGC), which is a powerful model for developmental genetics, and human cell lines. These systems have complementary advantages, so combined insights from studies on these systems can be applied to patients and human populations.

Studies in the Center focus on substance use disorders including cocaine, methamphetamine, and alcohol cardiovascular disease, cancer, and neurodegenerative disorders. Most genetic studies to date have focused on genes that code for proteins, structural components of our cells and enzymes that catalyze reactions that sustain intermediary metabolism and the formation of macromolecules, such as our DNA.

However, protein coding genes comprise only ~2% of the human genome and there is a growing realization that non-protein coding elements of the genome play an important role in gene regulation in health and disease.Thus, a major focus of the Centers studies is dedicated to elucidating the contributions of noncoding elements of the genome to disease manifestation. Another major focus of faculty in the Center is to develop computational methods to predict disease susceptibility based on genetic and environmental information, a critical prerequisite for personalized medicine. The Center also interacts closely with the GGC to obtain insights in the pathology of rare pediatric diseases.

The Clemson Center for Human Genetics seeks to develop local, regional, national, and international collaborations to advance human genetics and is currently part of a large international consortium funded by the European Commission to study the genetics of susceptibility to environmental toxins. As part of a major research university, the Center is also strongly committed to educating the next generation of human geneticists by providing educational opportunities for high school students, their teachers, undergraduate and graduate students, postdoctoral fellows and visiting scientists, and to promote public understanding of human genetics through community outreach.

View original post here:
SCBIO | An Inside Look at the Clemson Center for Human Genetics

NHGRIs social media platforms provide a great venue for conveying information about genomics to the general public, while also staying connected with colleagues and interested stakeholders. Social media provides NHGRI staff a space to talk about their work, make genomics topics easy to understand, and show how genomics can positively affect people. NHGRIs social media accounts on both Facebook and Twitter post information that is directed to the various NHGRI messages, such as those related to the 2020 NHGRI Strategic Vision, funding opportunities in genomics, the importance of genomic literacy, and the need to increase the diversity of the genomics workforce. In 2019, NHGRI increased its social media presence by starting a dedicated Twitter account for NHGRI director Dr. Eric Green, in addition to the institutes Twitter and Facebook accounts.

Every few weeks, the social media team hosts a #AskDrGenome session, during which a special guest and subject matter expert answers questions on Twitter about specific genomics topics, such as genomic medicine, polygenic risk scores, bioethics, genome sequencing, diversity of the genomics workforce, and genomic literacy. The next #AskDrGenome will be held on Wednesday, September 29, at 3 p.m. ET, during which NHGRI experts Laura Koehly, Ph.D., and Susan Persky, Ph.D., from the NHGRI Social and Behavioral Research Branch will answer questions about social science and augmented reality. Previous #AskDrGenome sessions can be found in the associated Twitter moments.

Twitter users can also test their knowledge about genomics by participating in pop quizzes on the @NHGRI_Directors account with the #PopQuizwithDrGenome series. For these quizzes, the social media team uses the NHGRI fact sheets to create poll questions on Twitter, which are later followed by a video of Eric Green giving the correct answer and talking more about the topic. So far, the series has featured questions about some genomics basics and comparative genomics.

The social media team uses a friendly and engaging voice to encourage the general public to learn more about genomics. Every Friday, the team creates a Twitter thread that breaks down genomics topics that are detailed in available factsheets on genome.gov, including gifs and imagery to make the topics fun for all audiences. Topics have included an introduction to genomics, polygenic risk scores, genome sequencing, chromosomes, and biological pathways. The team also creates #GenomeFacts that provide small bits of accessible information, such as what it will look like to implement genomic medicine. Previous Twitter threads from NHGRI #FactsheetFridays can be found in the associated Twitter moments.

Virtual broadcasts have also allowed NHGRI to host more events and gain a wider audience. Such events are livestreamed on NHGRI social media platforms, making the content easily accessible. Examples include upcoming Bold Predictions Seminars, Genomics and the Media Seminars, and National Advisory Council for Human Genome Research meetings. Viewers are also encouraged to ask questions on social media that may be featured during the Q&A portion of these virtual events. In addition to being livestreamed, the social media team live-tweets these events with information about the speakers, the discussion topic, and relevant quotes from the live event. Now that many genomics conferences and events are virtual, it allows the social media team to share relevant topics with NHGRI Twitter followers, thereby providing access to information that would not otherwise be easily found.

The NHGRI social media team is excited to connect with as many social media followers as possible. To see all of these activities and more, find our accounts on Facebook @genome.gov and on Twitter at @genome_gov and @NHGRI_Director.

Read the rest here:
NHGRI's social media activities bring genomics closer to the public - National Human Genome Research Institute