The two most common types of inflammatory bowel diseases are ulcerous colitis and Crohn’s disease. These are diagnosed by camera inside the gut, and by investigating small samples of the gut (biopsies). The diagnosis is often difficult, and if the wrong diagnosis is made, there may be severe consequences for the patients, because the treatments and medications are different between the two diseases.
The development of new and improved diagnostic methods is therefore important. The Sandelin group at Department of Biology/BRIC, University of Copenhagen has, in collaboration with clinicians from Herlev and Hvidovre hospitals and scientists from Roskilde University and the Technical University of Denmark, made new discoveries may contribute to improved methods for diagnosis.
– We do not know the molecular cause of these diseases. Much of what we know comes from genetic studies, where several key genes have been identified. However, 70% of genetic mutations that are linked to the diseases are located outside of genes that code for proteins. We believe that many of these mutations have an effect of the regulation of the genes, and thereby the disease, says Prof Sandelin who led the study, says Albin Sandelin, professor at Department of Biology, University of Copenhagen.
The scientists used a state-of-the-art method to map regulatory regions and their activity in patients with ulcerous colitis or Crohn’s disease and compared these with control subjects. They found that mutations associated to the disease were often located within regulatory regions active in the disease. This information is important for understanding the effect of such mutations. By combining these data with computer-based models and nano-fluidics technology, they could identify 35 regulatory regions whose activity could distinguish ulcerous colitis, Crohn’s disease and control subjects with high accuracy. These findings may open new avenues for new and improved diagnosis methods for inflammatory disease.

EurekAlertwww.eurekalert.org/pub_releases/2018-04/fos–nmf042618.php

Researchers at Rice University and the University of Texas MD Anderson Cancer Center have refined and, for the first time, run in vivo tests of a method that may allow nanotube-based probes to locate specific tumours in the body. Their ability to pinpoint tumours with sub-millimetre accuracy could eventually improve early detection and treatment of ovarian cancer.
The non-invasive technique relies on single-walled carbon nanotubes that can be optically triggered to emit shortwave infrared light.
For this study, the researchers used the technique to pinpoint small concentrations of nanotubes inside rodents. The lab of co-author Dr. Robert Bast Jr., an expert in ovarian cancer and vice president for translational research at MD Anderson, inserted gel-bound carbon nanotubes into the ovaries of rodents to mimic the accumulations that are expected for nanotubes linked to special antibodies that recognize tumour cells. The rodents were then scanned with the Rice lab’s custom-built optical device to detect the faint emission signatures of as little as 100 picograms of nanotubes.
The device irradiated the rodents with intense red light from an array of light-emitting diodes and read fluorescent signals with a specialized sensitive detector. Because different types of tissue absorb emissions from the nanotubes differently, the scanner took readings from many locations to triangulate the tumour’s exact location, as confirmed by later MRI scans.
Weisman said it should be possible to noninvasively find small ovarian tumours within rodents used for medical research by linking nanotubes to antibody biomarkers and administering the biomarkers intravenously. The biomarkers would accumulate at the tumour site. He said more refined versions of the optical scanner may then be able to locate a tumour within seconds, and further advances may extend the method’s application to human cancer detection. The new results suggested that antibody-nanotube probes could potentially detect tumours with as few as 100 ovarian cancer cells, which could make it a valuable tool for early detection.
Rice University
news.rice.edu/2017/11/30/researchers-advance-technique-to-detect-ovarian-cancer-2/

Researchers investigated genomes from diverse Chinese populations to identify new and known genetic variants that contribute to a person’s blood sugar level and risk of Type 2 diabetes. Karen Mohlke at the University of North Carolina at Chapel Hill, Wei Huang at the Chinese National Human Genome Center and Shanghai Industrial Technology Institute, and their colleagues report these findings.
Type 2 diabetes affects more than 422 million people worldwide and at least 30% of these cases occur in East Asian populations. A person’s risk of Type 2 diabetes, as well as the levels of blood sugar, insulin and HbA1c, which gives an average of recent blood sugar levels, are all inherited traits. The genetic variants that contribute to these traits can vary between populations, so researchers conducted genome-wide association analyses to identify these variants in up to 7,178 Chinese individuals from nine provinces who participated in the China Health and Nutrition Survey (CHNS). The study identified new variants and confirmed 32 previously described variants believed to contribute to Type 2 diabetes and blood sugar level, which vary in frequency across the population. The researchers also performed laboratory assays to show that one variant located in a gene regulatory element between the SIX2 and SIX3 genes reduces transcriptional activity and gene expression in pancreatic islets, leading to elevated blood sugar. "We compared variants linked to glucose level in East Asians with variants linked to islet gene expression levels in Europeans,"Dr. Mohlke explained. "This cross-ancestry comparison helped define a molecular mechanism that supports, in humans, a role for the SIX3 and/or SIX2 transcription factors affecting insulin secretion."
A next step in this work will be to investigate further the function of other genetic variants identified in the study to better understand how they contribute to blood sugar levels and risk of Type 2 diabetes. This work also highlights the usefulness of the diverse population within the CHNS for performing genetic studies. As researchers conduct more genome-wide meta-analyses across genetically diverse populations, they will likely identify additional genetic variants that will better explain the levels of heritability of complex traits like diabetes.
EurekAlertwww.eurekalert.org/pub_releases/2018-04/p-gvl032918.php

What role do genes play in egg, milk, and nut allergies? A study, led by the Max Delbrück Center for Molecular Medicine (MDC) and Charité – Universitätsmedizin Berlin, has found five genetic risk loci that point to the importance of skin and mucous membrane barriers and the immune system in the development of food allergies.
An estimated five to eight percent of all children suffer from food allergies. They usually appear in the first years of life and manifest themselves in the form of itchy rashes and facial swellings, which occur shortly after food ingestion. Food allergies can, however, also cause severe allergic reactions involving breathing difficulties, vomiting, or diarrhea, and are the most frequent triggers of anaphylaxis in children. Anaphylaxis is the most extreme form of an immediate allergic reaction and can be life threatening.
In Germany, chicken eggs, cow’s milk, and peanuts are the most common causes of allergic food reactions in children. Unlike allergies to cow’s milk and chicken eggs, which often disappear after a few years, children generally do not outgrow allergies to peanuts. Peanut allergy sufferers must follow a strict diet for their entire lives and carry emergency medication with them at all times.
The causes of food allergies involve a complex interplay of genetics and environment. “Studies of twins suggest that about 80 percent of the risk for food allergies is heritable, but little is known so far about these genetic risk factors,” says Prof. Young-Ae Lee, a researcher at the MDC and head of the Charité‘s outpatient pediatric allergy clinic.
A genome-wide association study examined some 1,500 children in Germany and the United States who suffer from food allergies. The research looked at more than five million genetic variations, called single nucleotide polymorphisms or SNPs (pronounced “snips”), in each participant in the study and compared the frequency of these SNPs with that of the control subjects. The study involved researchers from Berlin, Frankfurt, Greifswald, Hanover, Wangen, and Chicago. It is remarkable not only for its size but also for its reliable diagnostic methodology.
Unlike other studies, the researchers used an oral food challenge test to confirm the allergy diagnosis. This is a complex procedure in which patients ingest small amounts of the suspected allergen in the hospital under emergency conditions to determine if they respond allergically to it. “We know from clinical practice that as many as 80 percent of presumed food allergies are not actually allergies. These food sensitivities are frequently due to food intolerance rather than an allergic response,” says Prof. Lee.
This study discovered a total of five genetic risk loci for food allergies. Four of them show a strong correlation with known loci for not only atopic dermatitis and asthma, but also for other chronic inflammatory diseases like Crohn’s disease and psoriasis as well as autoimmune disorders.

New risk locus associated with all children’s food allergies
The so-called SERPINB gene cluster on chromosome 18 was identified as a specific genetic risk locus for food allergies. It involves ten members of the serine protease inhibitor (serpin) superfamily. The genes in this cluster are expressed primarily in the skin and in the mucous membrane of the oesophagus. The researchers thus suspect that they play a major role in ensuring the integrity of the epithelial barrier function. Another important finding of the study is that four of the five identified risk loci are associated with all food allergies. The human leukocyte antigen (HLA) region, which is specific to peanut allergy cases, appears to be the only exception.
The study provides a basis for the development of better diagnostic tests for food allergies and for further investigation into their causative mechanisms and possible treatment strategies. Parents should not make decisions about avoiding specific foods on their own, but should instead seek out a specialist if their child appears to have a food allergy.
Max Delbrück Center for Molecular Medicine (MDC)
insights.mdc-berlin.de/en/2017/10/study-provides-clarity-genetic-causes-childrens-food-allergies/

Researchers at The Johns Hopkins Kimmel Cancer Center have developed a test for urine, gathered during a routine procedure, to detect DNA mutations identified with urothelial cancers.
UroSEEK uses urine samples to seek out mutations in 11 genes or the presence of abnormal numbers of chromosomes that would indicate the presence of DNA associated with bladder cancer or upper tract urothelial cancer (UTUC).
The researchers said the test, when combined with cytology, the gold standard non-invasive test currently used for detection, significantly enhanced early detection for patients who are considered at risk for bladder cancer and surveillance of patients who had already been treated for bladder cancer.
“There were nearly 80,000 new cases of bladder cancer and more than 18,000 deaths in 2017,” said George Netto, M.D., a senior author on the UroSEEK paper, formerly at The Johns Hopkins University and currently chair of pathology at the University of Alabama-Birmingham. “This is about using the urine to detect the cancer. UroSEEK is a method of detection that many people have tried to find that is non-invasive.”
Most cancers are curable if they are detected early, and the researchers are exploring ways to use cancer gene discoveries to develop cancer screening tests to improve cancer survival. They announced the development of CancerSEEK, a single blood test that screens for eight cancer types, and PapSEEK, a test that uses cervical fluid samples to screen for endometrial and ovarian cancers.
UroSEEK is aimed toward early detection of bladder cancer in at-risk patients, those who may have blood in their urine or people who smoke, as well as patients who have already gone through a procedure to treat bladder cancer and need to be monitored for any recurrence of the disease.
“In almost one-third of patients, bladder cancer detection is late. The cancer has already gotten into the surrounding muscle,” Netto said. “Even in those detected at an earlier stage, the tumours frequently recur. Patients are committed to a lifelong surveillance that requires invasive cystoscopy procedures and biopsies and is costly.”
Saying current non-invasive approaches for detection of urothelial cancer are suboptimal, researchers wanted to develop a test for bladder and UTUC cancer that would allow it to be found sooner and cheaper than current methods using cytology, which is not particularly sensitive and does not do well in detecting low-grade bladder cancer or UTUC.
Researchers studied 570 patients who were considered at risk for bladder cancer and found UroSEEK was 83 percent positive in those who developed cancer. When combined with cytology, the sensitivity increased to 95 percent of patients who developed the disease.
“When you combine them, you get better results,” said Nickolas Papadopoulos, Ph.D., a senior author and an investigator at the Ludwig Center at Johns Hopkins. “Side by side, UroSEEK has better sensitivity. There are some cases when cytology detects when UroSEEK doesn’t. Combining them produces the best results.”
John Hopkins Kimmel Cancer Centerwww.hopkinsmedicine.org/news/media/releases/gene_based_test_for_urine_detects_monitors_bladder_cancer