Washington: New insights into how genetic factors affect the body's immune response in type 1 diabetes have recently been found.The findings, published in eLife, provide evidence of a direct link between genetic factors associated with susceptibility to type 1 diabetes and immune functionality, particularly involving immune T cells. They also highlight 11 genes which could be explored as potential candidates for new treatments.Type 1 diabetes develops when the body's immune system mistakenly attacks groups (or islets) of insulin-producing beta cells in the pancreas. There are currently over nine million people diagnosed with type 1 diabetes, but there is no cure and patients need to have regular insulin injections to manage the condition. People with certain genetic variations are more susceptible to type 1 diabetes. But while previous studies have identified around 60 associated variations, it is still unknown how they influence the condition."To characterise the body's immune response in type 1 diabetes, we need to look at both the proportion of immune cells and their production of proteins - cytokines - that stimulate the immune system," explains Xiaojing Chu, a Doctorate Student at the University Medical Center Groningen, the Netherlands. Chu is a co-first author of the study alongside Anna Janssen, a Medical Doctor and PhD Candidate, and Hans Koenen, Assistant Professor, at Radboud University Medical Center, the Netherlands. Xiaojing added, "In our study, we explored how genetic factors affect immune cells and their cytokine production in people with type 1 diabetes, as well as the differences between the immune response in patients and a healthy response." To do this, the researchers collected blood samples from 243 volunteers of Dutch descent with type 1 diabetes, aged 20-84 years old. They then applied a technique called genetic association analysis on more than 200 immune cell traits and more than 100 cytokine production profiles to identify genetic determinants of immune functionality. They compared the results to those obtained in a group of 500 healthy individuals from previous studies that characterised the impact of genetic factors on immune responses in these individuals.Their analyses showed that genetic variants determining susceptibility to type 1 diabetes significantly affect T-cell composition. Specifically, a group of these cells, called CCR5+ regulatory T cells, was actively involved in type 1 diabetes through an area of the genome called the constrained coding region.The team then used a technique called genome-wide quantitative trait loci (QTL) mapping to analyse immune traits. This revealed 15 genetic 'commands' that influence the behaviour of immune cells in type 1 diabetes. Of these, 12 have not previously been reported in healthy people, implying a disease-specific genetic regulation. Additionally, the team identified 11 genes as potential candidates for drug development. "Our findings provide a deeper understanding of the immune mechanisms involved in the development of type 1 diabetes and that affect the general inflammatory response in patients. We hope this work will open up new avenues for the development of much-needed treatments," concludes Yang Li, Professor of Computational Biology and Director of the Centre for Individualised Infection Medicine (CiiM), Helmholtz Centre for Infection Research, Hannover, Germany. Li is a co-senior author of the study alongside Cees Tack, Professor in Internal Medicine at Radboud University Medical Center, Nijmegen, the Netherlands.&nbsp;—ANI

New insights into how genetic factors affect the body's immune response in type 1 diabetes have recently been found.

Study Explores How Genetics Influence Immunity In Type 1 Diabetes Patients

Washington: Genetic signatures that can predict whether tumours in patients with bladder and other cancers will respond to immunotherapy have recently been identified by researchers from Cedars-Sinai Cancer.Their results were published in the peer-reviewed Journal of the National Cancer Institute, and could one day help guide clinicians to the most effective treatments for cancer patients."Our work indicates that these genetic signatures may prove to be tremendously valuable in predicting immunotherapy response in patients with bladder cancer, but also other tumour types," said Dan Theodorescu, MD, PhD, director of Cedars-Sinai Cancer, the PHASE ONE Foundation Distinguished Chair and senior author of the study. "We will continue investigating these biomarkers with the goal of bringing them into clinical use and improving patient outcomes."During the past five years, anti-PD-1/PD-L1 therapy--a type of cancer immunotherapy that paves the way for the body's immune system to attack tumour cells--has proved effective against many cancer types, according to Keith Syson Chan, PhD, a translational scientist, professor of Pathology and co-author of the study."It has proven very effective against melanoma and revolutionized lung cancer treatment," Chan said. "Bladder cancer is considered one of the more responsive tumour types, but still has just a 25% durable response rate, so improvement is still needed."When a tumour causes a host immune reaction, immune cells usually are able to infiltrate the core of the tumour, and scientists call it a "hot" tumour. Some tumours, on the other hand, block immune cells from infiltrating and are known as "cold" tumours.A previous study by Theodorescu implicated a gene--called discoidin domain receptor tyrosine kinase 2 (DDR2)--in contributing to anti-PD-1 resistance in animal models in several tumour types. In a collaboration between cancer biologists and bioinformatics researchers, this new study further investigated the DDR gene family using human cancer data sets in various tumour types.Sungyong You, PhD, a computational biologist with expertise in urologic oncology and the first author of the study, analyzed data from The Cancer Genome Atlas program, a publicly available database with information on hundreds of cancer samples, to look at how the expression of DDR2 and related gene DDR1 correlated with the host immune response to a tumour using bladder cancer as a model.He also looked at how genes regulated by DDR2 and DDR1 (i.e., gene signatures) correlated. He then looked at patient data from IMvigor 210, a clinical trial that evaluated immunotherapy response in bladder cancer, to see if these responses correlated with DDR2 and DDR1 expression or their related gene signatures.The investigators came away with two key findings.First, while the DDR1 and DDR2 genes are members of the same family, they have very different effects on tumours. Tumours with high expression of DDR1 tend to exhibit low expression of DDR2 and vice versa. And high DDR1 tumors are "cold," while high DDR2 tumors are "hot." Investigators also identified four unique gene signatures modulated by DDR1 and DDR2 that were closely associated with tumour response to immunotherapy. They checked these genetic signatures in several additional sets of publicly available patient data across multiple cancer types."We found that these gene signatures were clearly associated with response to immunotherapy in bladder cancer and lung cancer tumours in multiple patient groups," You said. "We also evaluated the signatures in publicly available data on melanoma, glioblastoma and blood cancers, with similar results.""The next step is to validate these signatures in a prospective clinical trial," said Theodorescu. "This could yield new tools that allow clinicians to determine pre-treatment whether given patients will likely respond to anti-PD-1/PD-L1 therapy. They can then proceed with anti-PD-1/PD-L1 therapy for those patients who will derive the most benefit, and offer alternative therapies for patients not likely to respond, improving outcomes for all."&nbsp;—ANI

 Genetic signatures that can predict whether tumours in patients with bladder and other cancers will respond to immunotherapy have recently been identified by researchers from Cedars-Sinai Cancer.

Bladder Cancer Immunotherapy Response Can Be Predicted By Genetics

Indiana (US): Humans are a diverse species. Each person on the earth has enough DNA to reach Pluto three times over. Studying how all of this genetic material works, and especially how genes impact human behaviour, is a very difficult effort aided by the introduction of large banks of genetic data and powerful data science analytical tools to analyse that data. Robbee Wedow, an assistant professor of sociology and data science in Purdue's College of Liberal Arts, an adjunct assistant professor of medical and molecular genetics in Indiana University's School of Medicine, and Purdue's inaugural faculty-in-residence at AnalytiXIN/16 Tech in Indianapolis, maps those miles of genes to gain insights into how genetics interacts with social forces and environments. He used genetic databases to investigate how single nucleotide polymorphisms, or SNPs, impact complex, encompassing qualities such as sexual behaviour, educational achievement, socioeconomic position, health behaviours, and others. "We know that social forces like socioeconomic status play a role in influencing a person's life and life outcomes," Wedow said. "But we also know there is a genetic component to every behavior. What we don't understand yet is how these biological forces interact with the environment and what these sorts of interactions might mean for social science -- and what we think we know about social science research to date. We are using well-powered genetic data to do more accurate and replicable social science and to explore what might be possible at the intersection of genetic and behavioral science." The real scope of genetics became clear when scientists sequenced the first human genome in 2003. Initially, geneticists believed that discovering a gene for each trait was as simple as looking in the appropriate spot. However, DNA bases and genes are not only keys of a grand piano on which human lives are performed like masterpieces. Instead, DNA functions more like a pipe organ, with stops, switches, and pedals that may alter the tone of notes, muffle them, or enhance their volume. Environment, diet, pollution, life experiences, and other factors may all influence when and how genes matter for specific outcomes, as well as whether parts of the genome matter at all. There is no one gene responsible for a behavioural consequence. Biology does not determine fate: while it does set out the musical score, musicians are free to improvise and interpret as they perform. The idea, Wedow stresses, is not that these genes control a person's life or destiny. Each SNP, in fact, has a very small effect on an overall outcome like educational attainment. No "Gattaca"-level reading of one's destiny from their genes -- in the style of the dystopian 1990s movie -- is on the horizon. Rather, being able to clarify the genetics of certain behaviors can help scientists understand the nuances of human behavior. "People think that genetics is always about biology, but in the case of sociogenomics it's more about using the advantages of this new, well-powered data to better understand the outcomes themselves, or about allowing researchers to do more accurate social science and behavioral research," Wedow said. "The social sciences have recently struggled with replicating studies. Oftentimes the sample sizes are too small for rigorous estimates and certainty. That's where the potential of using these huge banks of genetic data for the social sciences comes in. They help us get a much clearer, more certain look at what's really going on." Analyzing the genetics is only the first step. An American geneticist in the early 1800s could have correlated genetics with educational mastery and concluded that anyone with two X chromosomes tended to have less education. That is not because the chromosomes had anything at all to do with education. Rather, the correlation reflected social and gender biases present in the culture at the time. Similar insights lurk in Wedow's research. "Sociogenomics isn't necessarily about biology, like some might think," Wedow said. "When someone studies cancer genetics, they are studying it because they want to elucidate the biology of cancer; they want to figure out ways to better diagnose it, track it and treat it. But researchers in the field of sociogenomics want to study the genetics in order to do better social science. No one would ever study sociology without considering socioeconomic status and environment. We want to be able to take genetics into account in the same way." In a study in volume 7, No. 7 of the journal Nature Human Behaviour, Wedow, his co-corresponding author Andrea Ganna from the University of Helsinki, and his other co-authors looked at 109 survey questions in over 300,000 individuals to examine the ways that people's genes correlated with whether they answered certain questions or left them blank in surveys answered in the UK Biobank. That may sound fairly abstruse, but it fills a gap that the field of sociology has struggled with for decades. "How do you know what you don't know or how someone might have answered a question if they choose not to answer it?" Wedow said. "It turns out that the genetics of people who either answer the survey question, or do not, overlaps with the genetics of other outcomes like education, income or certain health behaviors." That means that scientists can use this type of data to get a better understanding of how people who choose not to answer questionnaires might also share similar responses to questions about health or social behaviors. Geneticists can also use the results of this study to correct for bias in genetic studies of any behavioral, psychiatric or medical outcomes. "We can't parcel out the signal from the noise yet or causally tease apart the effects of environment from the effects of biology," Wedow said. "We know the genetics correlate with certain outcomes, but we are not at a point where we can say any specific gene causes any one outcome. The effect of each individual gene is small. It's only in large data sets that we start to get the statistical power to get meaningful, reproducible results. We are using these new exciting, emerging data and tools to revolutionize social science." —ANI

Humans are a diverse species. Each person on the earth has enough DNA to reach Pluto three times over

Study Finds How Genetics Interacts With Social Forces, Environments

New York: Ecologists have proven that the genetic material that species shed into their environments can reveal not only the presence of the species but also a wide range of information about the genetics of whole populations — information that may assist scientists to trace the source of a new invasive population and prevent further invasion. The advancement in environmental DNA (eDNA) also opens new possibilities for protecting endangered and vulnerable species. “For the benefit of biodiversity conservation, we’re getting closer and closer to what forensic scientists do every day at crime scenes,” said study co-author David Lodge, director of the Cornell Atkinson Center for Sustainability. In the new study, published in the Proceedings of the National Academy of Sciences, the researchers demonstrated that their methodology was successful in field sampling of invasive round goby fish throughout the Great Lakes and the New York Finger Lakes. In their Great Lakes study, which involved collecting water and tissue samples from round goby fish in 13 locations from Lake Michigan to Oneida Lake, the researchers found that their eDNA sampling methodology can be used to detect nuclear genetic variations, making it possible to analyze genetic diversity and variation within species. This information is useful for natural resource managers because it can help them trace the source of a new invasive population as well as prevent further invasion or minimize harm by determining how invasive species are moving and how to stop them. The breakthrough can also help scientists understand the demographics of imperilled species without requiring the physical capture of animals that are already rare and vulnerable. Species experiencing population declines can suffer from a loss of genetic diversity, and eDNA may allow researchers to detect those declines earlier, according to the first author of the study, Kara Andres. Andres is a former graduate student in Lodge’s lab and now a postdoctoral fellow at Washington University in St Louis. She wrote the paper with co-authors Lodge and Jose Andrés, a Cornell Atkinson faculty fellow and a senior research associate who co-directs the Cornell Environmental DNA and Genomics Core Facility. “It is a major step in unlocking the full potential of genomics techniques when applied to aquatic eDNA samples,” Jose Andrés said. “In the near future, I anticipate that this technique will allow us to study the status and health of elusive species. I believe this holds profound implications, particularly in marine environments.” —ANI

Ecologists have proven that the genetic material that species shed into their environments can reveal not only the presence

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Study Explores How Genetics Influence Immunity In Type 1 Diabetes Patients

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Tag : Genetics

Study Explores How Genetics Influence Immunity In Type 1 Diabetes Patients

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