Breaking News
August 20, 2018 - New assay may help improve both sarcoma diagnosis and treatment
August 20, 2018 - New class of insect repellents to fight against mosquito-borne diseases
August 20, 2018 - ACA Coverage Gains Include Workers Without Insurance
August 20, 2018 - 3-D printed biomaterials for bone tissue engineering
August 20, 2018 - Prenatal exposure to acute stress can affect cognitive function in children of low-income households
August 20, 2018 - Researchers find long-term structural, functional brain abnormalities in individuals with AUDs
August 20, 2018 - Shortage of insurance fraud cops sparks campaign debate
August 20, 2018 - Researchers find STAT3 as therapeutic target for chronic active EBV infection
August 20, 2018 - Health Tip: Keep Diabetic Feet Healthier
August 20, 2018 - FDA approves brain stimulation device for OCD
August 20, 2018 - NYU Langone’s Perlmutter Cancer Center expands Blood and Marrow Transplant Program
August 20, 2018 - New drug shows potential to prevent painful side effect of therapy
August 20, 2018 - RDMD raises $3 million in seed funding to accelerate rare disease research, drug development
August 20, 2018 - Illicit drug use is higher during celebratory events, may be worse than previously thought
August 20, 2018 - Exploring the relationship between fever and cancer incidence
August 20, 2018 - Study reveals how socioeconomic status affects racial, ethnic disparities in childhood cancer survival
August 20, 2018 - Brain tumors trap immune cells needed to fight cancer in the bone marrow, finds research
August 20, 2018 - Three factors that contribute to physician burnout
August 20, 2018 - Babies dependent on opioids need touch, not tech
August 20, 2018 - Understanding How Antibodies Shape the Gut Microbiome
August 20, 2018 - Cara Therapeutics Doses First Patient in Second Pivotal Phase 3 Efficacy Trial of Korsuva (CR845/difelikefalin) Injection in Hemodialysis Patients with Chronic Kidney Disease-Associated Pruritus
August 20, 2018 - Kidney transplant chains more effective in saving lives
August 20, 2018 - Study unravels cellular and molecular mechanisms behind dermal condensate formation
August 20, 2018 - New integrated gene logic-chips could have great value in medical care
August 20, 2018 - FDA Advisory Committee Recommends Approval of Paratek’s Omadacycline
August 20, 2018 - Total, open repairs decline for abdominal aortic aneurysms
August 20, 2018 - Novel system can pinpoint ingestible implants inside the body using wireless signals
August 20, 2018 - Infection rates of high risk oral HPV in England found to be lower than expected
August 20, 2018 - Making robots as valuable and trustworthy assistants for medical therapies
August 20, 2018 - Patients with low-risk blood clots can be better treated at home than at hospital
August 20, 2018 - Passive smoking exposure among kids greatly increases COPD risk late in life
August 20, 2018 - Primary Care Provider Burnout Rate Low in Small Practices
August 20, 2018 - Discovery presents treatment hope for Alzheimer’s and other neurodegenerative diseases
August 20, 2018 - Stroke patients appear to receive better care at teaching hospitals with less chance of readmission
August 20, 2018 - Distinct origin of ADHD identified In children with history of traumatic brain injury
August 20, 2018 - AHA: Wildfire Smoke Threatens Health of Those Near and Far
August 20, 2018 - Here’s a mental health workout that’s as simple as ABC
August 20, 2018 - Newly discovered cytoskeleton utilized by cancer cells for survival
August 19, 2018 - Bifidobacteria supplement colonizes gut of breastfed infants
August 19, 2018 - Why patients with Alzheimer’s markers never develop the condition
August 19, 2018 - ACA’s Medicaid expansion associated with increase in prescriptions for opioid use disorder treatment
August 19, 2018 - Important factor may be missing in models used to predict spread of epidemics from climate change
August 19, 2018 - Indian-Americans have fewer sudden infant deaths, study finds
August 19, 2018 - Experts advise against universal genomic screening of newborns
August 19, 2018 - New trial to investigate whether weight loss before conception can make mom and baby healthier
August 19, 2018 - Sun Pharma Announces FDA Approval of Cequa (cyclosporine) Ophthalmic Solution to Treat Dry Eye Disease
August 19, 2018 - Researchers examining Parkinson’s resilience
August 19, 2018 - HPI, INTEGRIS and USPI enter into agreement to offer patients more choice, flexibility of care
August 19, 2018 - Researchers find mechanism that prepares brain to replicate repeated actions
August 19, 2018 - Those who are emotionally stable when young may remain the most stable as they age
August 19, 2018 - URI professor develops simpler and quicker method for detecting impurity in heparin
August 19, 2018 - Mayo Medical Laboratories and NDSC collaborate to develop new patient blood-management solution
August 19, 2018 - Insight into endocrine cancers and treatment options
August 19, 2018 - HPV Legislation Doesn’t Impact Teen Sexual Behaviors
August 19, 2018 - Exenatide treatment alleviated symptoms of depression in patients
August 19, 2018 - Tufts researchers win grant to study integration of genomic sequencing into neonatal care
August 19, 2018 - Novel finger-prick test can help prevent toxoplasmosis
August 19, 2018 - Cosmetic Procedures Boost Well-Being, Poll Shows
August 19, 2018 - Responsive parenting intervention results in lower BMIs through age three
August 19, 2018 - Anticancer drugs can help plants to battle infection
August 19, 2018 - Sunscreen from bathers releases significant quantities of polluting titanium dioxide into the sea
August 19, 2018 - Case Western Reserve gets three-year grant to enhance food systems in Cleveland neighborhoods
August 19, 2018 - Teenagers can thank their parents’ positive attitude for avoiding obesity
August 19, 2018 - Body mass index positively linked with blood pressure
August 19, 2018 - New tool fills gap in Small Molecules market
August 19, 2018 - Study compares survival outcomes in rural and urban cancer patients enrolled in clinical trials
August 19, 2018 - Researchers develop molecular matrix that delivers healing stem cells to injured elderly muscles
August 19, 2018 - Teva and Regeneron Announce Positive Topline Phase 3 Fasinumab Results in Patients with Chronic Pain from Osteoarthritis of the Knee or Hip
August 19, 2018 - New study pinpoints ways to improve quality of food and nutrition research
August 19, 2018 - Ology Bioservices wins $8.4 million worth agreement to manufacture anti-Ebola monoclonal antibody
August 19, 2018 - New CRISPR technology may help eliminate mutated gene sequence
August 19, 2018 - “Zombie gene” protects elephants from cancer finds study
August 19, 2018 - Study explores how many American cities protect the rights of employed breastfeeding mothers
August 19, 2018 - FDA Approves Lenvima (lenvatinib) for First-line Treatment of Unresectable Hepatocellular Carcinoma (HCC)
August 19, 2018 - Pain: Considering Complementary Approaches (eBook)
August 19, 2018 - Autoimmune response drives vision loss in glaucoma
August 19, 2018 - Tandem Diabetes Care introduces t:slim X2 Insulin Pump with Basal-IQ Technology in the US
August 19, 2018 - Innovative platform developed to destroy cancer cells
August 19, 2018 - Lowering pH inside tumor cells can slow down spread of cancer
August 19, 2018 - Biomarker predicts kidney cancer risk years before diagnosis
Role of genetics behind immune disease risk could be missed, scientists suggest

Role of genetics behind immune disease risk could be missed, scientists suggest

image_pdfDownload PDFimage_print

The role of genetics in the risk of having an immune disease could be missed in research, scientists suggest. Using a combination of stem cells and novel analytical tools, scientists at the Wellcome Sanger Institute and their collaborators discovered that clues to the contribution of genetic variation to disease risk lie not only in the genes, but also in the molecular switches that control those genes.

The results, published today (29 January) in Nature Genetics, show for the first time how immune cells created from human induced pluripotent stem cells (HiPSCs) can model immune response variation between people.

Researchers discovered that the differences in immune responses due to genetic variation were only visible at certain stages of the experiment when the immune cells were in particular states, for example when they were activated.

In other states, only ‘footprints’ of the genetic variation effects could be seen. However by looking at two elements, the genes and regulatory regions – the molecular ‘switches’ that control the expression of those genes, the researchers were able to identify the true impact of genetic differences on immune response.

The results suggest that the actual effects of genetic variation on immune response are often hidden if not searched for thoroughly.

An understanding of the role genetic variants play in helping our immune systems fight diseases is an important step towards better targeted therapies.

Dr Dan Gaffney, senior author from the Wellcome Sanger Institute, said: “We have found that the impact of genetic variants on how people’s immune cells respond to a pathogen like Salmonella are condition-specific – they are only visible at certain stages of infection. This means that the effects of genetic differences in immune disorders could be missed in research, if scientists aren’t studying both the genes and their control regions, the regulatory elements, of immune cells at all stages of an infection.”

In the study, scientists differentiated human induced pluripotent stem cells into white blood cells called macrophages. The macrophages were then studied in four different states: unstimulated, after 18 hours of stimulation with a signalling molecule interferon-gamma, after five hours infection with Salmonella, and after interferon-gamma stimulation followed by Salmonella infection.

Dr Kaur Alasoo, previously from the Wellcome Sanger Institute and now from the University of Tartu, Estonia, said: “A benefit of using stem cells rather than pre-existing blood cells is they’re very flexible, and enabled us to study the effects of stimulation at two different levels. We analysed which genes in the genome were expressed during each stage of infection, but also looked at the activity of enhancers – the molecular ‘switches’ that controlled the expression of those genes. This novel combination of tools enabled us to see otherwise hidden effects of genetic variation on immune response.”

The team also discovered that genetic variation impacts on the readiness of the immune cells to tackle an infection. In particular, some individuals’ immune cells were ready to deal with the Salmonella infection, whereas other individuals’ macrophages were less ready and took longer to respond. This level of ‘readiness’ was due to a phenomenon known as enhancer priming, where some of the switches were already turned on in the unstimulated cells to facilitate a quicker response. In some cases, the immune cells could be overly eager and this can lead to an inflammatory response associated with immune disorders.

Professor Gordon Dougan, from the Wellcome Sanger Institute, added: “If the genetic variant being studied is associated with disease, such as an immune disorder, one needs to be sure of which gene the variant is affecting in order to develop an effective therapy. This may only be visible in a small time-window of the infection. These results offer important new insights into studying the mechanisms behind infection and disease.”

Source:

http://www.sanger.ac.uk/news/view/hidden-genetic-effects-behind-immune-diseases-may-be-missed-study-suggests

Tagged with:

About author

Related Articles