(Press-News.org) Many genetic variants have been found to have a linkage with genetic diseases, but the understanding of their functional roles in causing diseases are still limited. An international research team, including a biomedical scientist from City University of Hong Kong (CityU), has developed a high-throughput biological assay technique which enabled them to conduct a systematic analysis on the impact of nearly 100,000 genetic variants on the binding of transcription factors to DNA. Their findings provided valuable data for finding key biomarkers of type 2 diabetes for diagnostics and treatments. And they believe that the new technique can be applied to studies of variants associated with other genetic diseases.
The study was co-led by Dr Yan Jian, Assistant Professor in the Department of Biomedical Sciences at CityU, Professor Bing Ren from the University of California San Diego and Professor Jussi Taipale from the University of Cambridge. Their findings were published in the prestigious scientific journal Nature, titled "Systematic analysis of binding of transcription factors to noncoding variants".
"Based on our findings, we believe that our high-throughput experimental method can be applied in the study of different genetic diseases, including colorectal cancer and prostate cancer. It can help dissect the mechanism of the genetic inheritance of the disease and find the biomarkers for clinical diagnosis," said Dr Yan.
Unveiling the roles of noncoding variants in diseases
Genome-wide association studies (GWAS), which investigate the entire genome, has been the most important strategy in finding the genes associated with complex genetic diseases. Researchers have found hundreds of thousands of genetic variants in association with human diseases and traits. But studies on the functions of these variants are still limited.
"Understanding the molecular functions of the noncoding variants will help us find out why people carrying these mutations are more susceptible to genetic diseases. This will help us develop methods or strategies to prevent, to detect or to cure the diseases early," explained Dr Yan.
One of the variants' functions is to affect the binding of transcription factors to DNA. The transcription factors will then control the gene expression in cells, turning the specific genes "on" and "off", modulating the cellular functions.
To systematically characterise the effects of genetic variants on the transcription factor binding, the team modified their previously developed experimental method into an ultra-high-throughput multiplex protein-DNA binding assay, termed "single-nucleotide polymorphism evaluation by systematic evolution of ligands by exponential enrichment" (SNP-SELEX). Then they chose the genetic variants from the gene locations on the genome (called "gene loci") that are known to be associated with the risk of type 2 diabetes as the object of analysis.
Utilising the SNP-SELEX, they successfully analysed the impact of 95,886 genetic variants on the binding of 270 distinct human transcription factors to DNA. They demonstrated that noncoding genetic variant SNP rs7118999 that increases the risk of type 2 diabetes can affect the DNA binding with one of the transcription factors, and the resulting molecular mechanism regulates the blood lipid level.
"This is a clear example of applying the data generated by SNP-SELEX that it can help identify the genetic variants which play key roles in the inheritance of type 2 diabetes. This would help the subsequent investigation in finding diagnostic biomarkers and therapeutic targets," said Dr Yan.
Speeding Up Analysis Significantly
Moreover, previous studies could only single out one or a few variants to find out its molecular mechanism. Each study took around 2-3 years. "So it was impossible to completely understand the complex genetic diseases like type 2 diabetes which are associated with hundreds of genetic variants within a short period. But with the SNP-SELEX, we could systematically analyse approximately 100,000 variants within a much shorter timeframe," said Dr Yan.
"In this study, we only covered a relatively small portion of variants and transcription factors. So we will expand our study. By utilising the SNP-SELEX, hopefully it will help us uncover the underlying mechanisms of more and more of these noncoding variants very soon," said Professor Ren.
INFORMATION:
Dr Yan, Dr Qiu Yunjiang from the University of California San Diego and Dr André M. Ribeiro dos Santos from the Federal University of Pará in Brazil are the paper's co-first authors. Dr Yan, Professor Ren and Professor Taipale are the co-corresponding authors. Other team members include researchers from Karolinska Institutet, University of Cambridge, University of California San Diego and CityU, coming from US, UK, Sweden, Brazil, China and Hong Kong.
https://www.cityu.edu.hk/research/stories/2021/02/24/efficient-systematic-genetic-analysis-helps-dissect-disease-inheritance
Long-term use of a medication used to treat kidney transplant patients may not be necessary in individuals with low-to-moderate risk of organ rejection, according to the results of a study led by a University of Cincinnati transplant researcher.
The randomized clinical trial of 385 patients on immunosuppressive drugs tacrolimus and mycophenolate examined whether use of these medicines called corticosteroids could be eliminated at seven days after kidney transplantation. The study shows that 15 years after transplantation no difference in kidney transplant survival or patient survival rates were found between patients who received long-term corticosteroids versus those who had corticosteroid eliminated early, explains E. Steve Woodle, MD, the William ...
MEMPHIS, TN, FEBRUARY 24, 2021:- Early diagnosis of Alzheimer's disease has been shown to reduce cost and improve patient outcomes, but current diagnostic approaches can be invasive and costly. A recent study, published in the Journal of Alzheimer's Disease, has found a novel way to identify a high potential for developing Alzheimer's disease before symptoms occur. Ray Romano, Ph.D., RN, completed the research as part of his Ph.D. in the Nursing Science Program at the University of Tennessee Health Science Center (UTHSC) College of Graduate Health Sciences. Dr. Romano conducted the research through the joint laboratory ...
Plants and animals can rapidly respond to changes in their environment, such as a Venus flytrap snapping shut when a fly touches it. However, replicating similar actions in soft robots requires complex mechanics and sensors. Now, researchers reporting in ACS Applied Materials & Interfaces have printed liquid metal circuits onto a single piece of soft polymer, creating an intelligent material that curls under pressure or mechanical strain. Watch a video of the smart material here.
Ideally, soft robots could mimic intelligent and autonomous behaviors ...
What The Article Says: This JAMA Insights review from Centers for Disease Control and Prevention COVID-19 Response team members presents data on the number of long-term care facilities and the numbers of residents and staff of those facilities who received first-dose vaccination through mid-January under the agency's public-private partnership with CVS, Walgreens and Managed Health Care Associates.
Authors: Radhika Gharpure, D.V.M., M.P.H., of the COVID-19 Response at the CDC, is the corresponding author.
To access the embargoed study: Visit ...
Coprolites, or fossilized dog feces, are often used to understand the dietary preferences of ancient civilizations. However, the samples are often contaminated, making the analysis difficult. A new study, published in END ...
PHILADELPHIA -- A second study of the injectable anti-obesity medication, semaglutide, has confirmed the large weight losses reported in a study earlier this month, establishing the reliability and robustness of this new drug. With obesity affecting more than 40 percent of American adults, the findings could have a major impact on weight management in primary care and other settings. The END ...
To become climate neutral by 2050, the European Union launched two ambitious programmes: "Green Deal" and "DigitalStrategy". As a key component of their successful implementation, climate scientists and computer scientists launched the "Destination Earth" initiative, which will start in mid-?2021 and is expected to run for up to ten years. During this period, a highly accurate digital model of the Earth is to be created, a digital twin of the Earth, to map climate development and extreme events as accurately as possible in space and time.
Observational data will be continuously incorporated into the digital ...
SAN ANTONIO -- Feb. 24, 2021 -- A Southwest Research Institute® (SwRI®) scientist examined 11 Mars years of image data to understand the seasonal processes that create linear gullies on the slopes of the megadune in the Russell crater on Mars. In early spring images, captured by two different cameras on the Mars Reconnaissance Orbiter, SwRI's Dr. Cynthia Dinwiddie noticed airborne plumes of dusty material associated with the linear dune gullies on the sand dune's downwind slope. These clues point to active processes involving chunks of frozen CO2, or dry ice, sliding down the sand dune, kicking up sand and dust along the way.
Russell crater, on Mars, ...
Meat alternatives are officially mainstream. To wit, Burger King added the plant-based Impossible Burger to its menu nationwide in 2019, and McDonald's plans to unveil its own McPlant in 2021. Alongside these vegetarian options, many companies are also working to culture meat outside of animals grown from cell lines. Proponents highlight a range of potential environmental and health benefits offered by this emerging industry, and several companies believe that these benefits could also play out with seafood.
A multidisciplinary team of researchers has taken a good, hard look at what it would take for cell-based seafood to deliver conservation benefits. They have ...
Immunologists at St. Jude Children's Research Hospital have discovered that tumors use a unique mechanism to switch on regulatory T cells to protect themselves from attack by the immune system. Surprisingly, the mechanism does not affect regulatory T cell function outside the tumor and may therefore limit the immune-associated toxicities of targeting regulatory T cells.
The finding offers the promise of drug treatment to selectively shut down regulatory T cells in a tumor, rendering the tumor vulnerable to cancer immunotherapies that activate the immune ...
