DNA: Past to Present 2017

National DNA Day is not only a celebration of the structure and sequence of the double-helix, but also the tireless commitment of researchers to understand the complexities of our genetic blueprint. As we revel in all things DNA, the GEN editorial staff has assembled a brief video timeline highlighting significant dates in DNA discovery.

Read more: DNA - Past to Present 2017

Source: GenEngNews

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FISHing in the Genomic Testing Age !

Genetic analysis has come a long way; we now have an ever-expanding collection of analytical tools in the diagnostic laboratory. So why do we still need a technique that usually only looks at one or two loci? The simple answer is that results from fluorescence in-situ hybridization (FISH) can quickly confirm diagnoses, guide clinicians’ judgements regarding differential diagnoses, and correlate results with clinical risk—thus enabling an informed choice of treatment type and intensity.

FISH employs fluorescently-labeled DNA probes to bind complementary DNA sequences within an interphase cell, or onto metaphase chromosomes. These sequences can then be visualized using fluorescent microscopy. The number, location and relative positions of the probe signals indicate chromosomal changes in a particular cell (Figure 1).

Many clinical trials use cytogenetic and FISH data to stratify patients according to specific risk factors. FISH is often used as a stand-alone technique for investigating abnormalities and following-up such patients, which, alongside its relatively low expense, makes it a very convenient investigative tool.

In this article we will explore the utility of FISH in today’s clinical laboratory and the future of the technique in the evolution of molecular testing.

Figure 1. The FISH process.

Figure 2. Interphase cell showing amplified HER2 signal pattern.

Read more: FISHing in the Genomic Testing Age !

Source: MedicalLaboratoryObserver

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Improving Diagnosis of Zika Virus Infection for Pregnant Women !

Mosquito-borne Zika virus (ZIKV) was the cause of the recent large outbreak of Zika disease in America. Despite fever, Zika is a mild disease, although epidemics in recent years have demonstrated an association with the appearance of severe congenital malformations (microcephaly). Owing to ZIKV serology cross-reactivity with other tropical flaviviruses, the final diagnosis relies on nucleic acid amplification. Pregnant women in endemic areas should be investigated to follow infection and sequelae.

Background

Zika virus (ZIKV) belongs to the Flavivirus genus and is related to other viruses that are also transmitted by the bite of mosquitoes, such as dengue virus (DENV), yellow fever virus (YFV) and West Nile virus (WNV). The Flaviviridae family comprises single-strand RNA, membrane-enveloped viruses that frequently use Aedes aegypti as a vector. Despite ZIKV being discovered over 60 years ago, only since 2014 (in the French Polynesia Islands) and 2015 (Brazil and America) has it been evident that the virus can cause large outbreaks and epidemics that lead to a global public health emergency.

Read more: Improving Diagnosis of Zika Virus Infection for Pregnant Women !

Source: ClinicalLaboratoryInternational

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High-Sensitivity Assays for Troponin in Patients with Cardiac Disease !

Troponin is a widely used biomarker in patients with cardiac disease. The use of troponin is well established in patients with suspected acute myocardial infarction (AMI), but troponin measurement is also used in other acute and nonacute settings. In patients with suspected AMI, early decision-making is crucial to allow rapid treatment and further diagnostic evaluation. Current guidelines recommend serial measurements of troponin with a cut-off concentration at the 99th percentile to triage patients in the emergency department.

Newer, high-sensitivity assays for troponin enable the detection of distinctly lower concentrations. Using these assays and very low cut-off concentrations, several rapid diagnostic strategies have been reported to improve diagnosis in acute cardiac care. Furthermore, noncoronary and non-acute applications of troponin assays — for example as a biomarker in patients with heart failure, pulmonary embolism, or stable coronary artery disease — are on the horizon and might improve individual risk stratification.

In this Review, we provide an overview on the development of high-sensitivity assays for troponin, and their application in patients with cardiac disease.

Pathophysiological background of troponin and troponin release

in different settings. A schematic overview of myocardial structure

related to troponin (inset), as well as the plasma troponin concentrations 

in different clinical settings (young and healthy, elderly or chronic diseases,

myocardial injury, and myocardial infarction).

Read more: High-Sensitivity Assays for Troponin in Patients with Cardiac Disease !

Source: NatureReviewsCadiology

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Non-Invasive Alternative To Amniocentesis? Experimental Test May Let Screen For Genetic Defects 5 Weeks Into Pregnancy

An experimental test that relies on an old-fashioned screening exam — the pap smear — may someday allow doctors to easily detect birth defects sooner than ever.

On Tuesday, Wayne State University (WSU) researchers revealed the latest encouraging findings on their creation, called “Trophoblast Retrieval and Isolation from the Cervix,” or TRIC for short. Using a pap smear, they scraped trophoblasts — the cells that eventually help form a fetus’ placenta — from pregnant women’s cervixes and genetically sequenced the fetal DNA found inside with next generation technology. They then compared these samples to those obtained from the mother, placenta, and fetus via conventional means.

Not only were the TRIC samples mostly made out of fetal DNA, indicating the low risk of contamination, but they matched up perfectly with the other fetal samples, validating the test’s overall accuracy. Even more importantly, the samples were taken as early as 5 weeks into pregnancy, blowing past the limit of other, invasive screening tests, such as amniocentesis, which can only be given starting at the end of the first trimester, 14 to 16 weeks in.

Researchers have developed a test that may be able to screen for birth defects
as early as five weeks into pregnancy.

Read more: Non-Invasive Alternative To Amniocentesis? Experimental Test May Let Screen For Genetic Defects 5 Weeks Into Pregnancy

Source: MedicalNewsToday

Pneumonitis: Symptoms, Causes, and Treatments.

Pneumonitis is a disorder where a person has an allergic reaction in their lungs caused by certain inhaled substances. The condition is also referred to as hypersensitivity pneumonitis.

The reaction they have to these substances can cause air sacs in one or both lungs to become inflamed. If untreated, the condition can cause long-term damage to the lungs. However, pneumonitis can be completely reversed if action is taken quickly. 

In this article, we take a look at the symptoms, causes, and treatments of pneumonitis. We also examine the differences between the condition and the more familiar pneumonia.

Symptoms of pneumonitis include shortness of breath, rattling sounds
in the lungs, and coughing.

Read more: Pneumonitis: Symptoms, Causes, and Treatments.

Source: MedicalNewsToday

Serum Level Measurements Improve Disease Risk Prediction.

Results obtained by using a commercially available uromodulin ELISA kit to analyze serum samples from individuals at risk for heart and circulatory system diseases indicated that this kidney-specific protein is a biomarker not only for kidney disease but also for cardiovascular diseases.

The glycoprotein uromodulin, also known as Tamm-Horsfall protein (THP), is synthesized exclusively in the kidneys and subsequently secreted. Low uromodulin concentrations in serum are a sensitive indicator for a loss of kidney function and thus play a role in the diagnosis of various renal diseases (nephropathies). When renal function is impaired, the uromodulin concentration in the serum sinks rapidly. Therefore, renal functional disorders can be identified at a very early stage of kidney damage, even in cases with few symptoms.

Uromodulin -a biomarker not only for kidney disease but also for cardiovascular diseases.

Read more: Serum Level Measurements Improve Disease Risk Prediction.

Source: LabMedica

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The Theory of Disappearing Microbiota and the Epidemics of Chronic Diseases.

In the present era, medical scientists have been confounded by the increasing incidence of multiple diseases across the world, beginning first in developed countries, and gradually spreading to other areas as they develop. These include the rises in cases of obesity, asthma, hay fever, food allergies, inflammatory bowel disease, juvenile (type 1) diabetes and autism, among many others. Are these diseases, which affect different body systems, unrelated or can a unified theory explain the increased incidence of all of these?

I believe that the latter possibility is true, and that the central theory to explain why these diseases have arisen and by what mechanism is based on modern changes in early life events that are related to the human microbiome. According to this theory, the microbiome of humans and of other animals is not accidental, but has been selected over long time periods to optimize host reproductive success through interactions between the microbiota and host physiology. Early life is the crucial period during which the adult microbiome becomes established, and development of the host and of the microbiota occur together in a conjoined manner through a dynamic equilibrium that follows a well-choreographed path. In early life, the context is set for the important developmental decisions that are required for the immune system to distinguish between what is self and what is not self, for metabolic organs to partition how much energy to expend or to save, and for the brain to determine how to respond socially to a person who might be either a friend or a foe.

Read more: The theory of disappearing microbiota and the epidemics of chronic diseases

Figure 1: A model for the interaction of the inherited microbiota with
early life immunological development in past and present children.

Source: NATURE REVIEWS IMMUNOLOGY

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Heterogeneity in Tuberculosis.

Infection with Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), results in a range of clinical presentations in humans. Most infections manifest as a clinically asymptomatic, contained state that is termed latent TB infection (LTBI); a smaller subset of infected individuals present with symptomatic, active TB. Within these two seemingly binary states, there is a spectrum of host outcomes that have varying symptoms, microbiologies, immune responses and pathologies. Recently, it has become apparent that there is diversity of infection even within a single individual. A good understanding of the heterogeneity that is intrinsic to TB — at both the population level and the individual level — is crucial to inform the development of intervention strategies that account for and target the unique, complex and independent nature of the local host–pathogen interactions that occur in this infection. In this Review, we draw on model systems and human data to discuss multiple facets of TB biology and their relationship to the overall heterogeneity observed in the human disease.

Read more: Heterogeneity in Tuberculosis.

Figure 1: A classical tuberculosis granuloma. The hallmark tuberculosis
granuloma is a highly organized collection of immune cells that aggregate
around a central necrotic core.

Source: NATURE REVIEWS IMMUNOLOGY

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Association Between Genetic Variation And Influenza Severity.

It is estimated that in the USA influenza -related deaths in recent years have ranged from 12,000 to 56,000. Factors like age, obesity, pregnancy and such chronic health conditions as asthma, chronic lung disease and heart disease are associated with an elevated risk of complications and death.

However, there are no proven genetic markers of influenza risk with an established mechanism of action. Interferon Induced Transmembrane Protein 3 (IFITM3) is an anti-viral protein that helps to block influenza infection of lung cells and to promote survival of the killer T cells that help clear the infection in the airways.

Image: A scanning electron micrograph of a CD8+ T cell engaging a virus.

(Photo courtesy of Dennis Kunkel).

A group of scientists collaborating with those at St. Jude Children's Research Hospital (Memphis, TN, USA) searched for other possible IFITM3 variants that correlated with gene expression, levels of the IFITM3 proteins and were common in influenza patients in the USA. The search led to an IFITM3 variant known as rs34481144. They checked 86 children and adults in Memphis with confirmed influenza infections and found two-thirds of patients with the most severe symptoms carried at least one copy of the newly identified high-risk IFITM3 variant. The high-risk variant was found in just 32% of patients with milder symptoms.

The team also found an association between the newly identified high-risk variant and severe and fatal influenza infections in 265 critically ill pediatric patients hospitalized in one of 31 intensive care units nationwide. The patients did not have health problems that put them at high risk for severe influenza. Of the 17 patients in this group who died from the infection, 14 carried at least one copy of the newly identified high-risk variant. Further study revealed how binding differed between the high-risk and protective variants. Those differences led to lower levels of the IFITM3 protein in individuals with two copies of the high-risk gene variant compared to other patients. The Memphis influenza patients also had fewer of the killer T cells in their upper airways. The study identifies a new regulator of IFITM3 expression that associates with CD8+ T cell levels in the airways and a spectrum of clinical outcomes.

Paul Thomas, PhD, an immunologist and corresponding author of the study, said, “A genetic marker of influenza risk could make a life-saving difference, particularly during severe influenza outbreaks, by helping prioritize high-risk patients for vaccination, drug therapy and other interventions. These results raise hopes that this newly identified IFITM3 variant might provide such a marker.” The study was published on July 17, 2017, in the journal Nature Medicine.

Source: labmedica