Whole genome sequencing reveals genetic structural secrets of schizophrenia

Most research about the genetics of schizophrenia has sought to understand the role that genes play in the development and heritability of schizophrenia. Many discoveries have been made, but there have been many missing pieces. Now, researcher have conducted the largest-ever whole genome sequencing study of schizophrenia to provide a more complete picture of the role the human genome plays in this disease & suggests that rare structural genetic variants could play a role in schizophrenia. These studies give snapshots of the genome, leaving a large portion of the genome a mystery, as it potentially relates to schizophrenia. In particular, this study highlighted the role that a three-dimensional genome structure known as topologically associated domains (TADs) could play in the development of schizophrenia. TADs are distinct regions of the genome with strict boundaries between them that keep the domains from interacting with genetic material in neighboring TADs. Shifting or breaking these boundaries allows interactions between genes and regulatory elements that normally would not interact. When these interactions occur, gene expression may be changed in undesirable ways that could result in congenital defects, formation of cancers, and developmental disorders. This study found that extremely rare structural variants affecting TAD boundaries in the brain occur significantly more often in people with schizophrenia than in those without it. Structural variants are large mutations that may involve missing or duplicated genetic sequences, or sequences that are not in the typical genome. This finding suggests that misplaced or missing TAD boundaries may also contribute to the development of schizophrenia. This study was the first to discover the connection between anomalies in TADs and the development of schizophrenia.

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                        Nasal smear as an allergy screening test

In the world of allergy diagnostics, the familiar blood samples and unpleasant skin prick procedures for testing allergen tolerance may soon be a thing of the past. A team of researchers has demonstrated that sufficient quantities of allergy antibodies for a diagnosis can be effectively measured in nasal secretions. Researcher has now tested a new diagnostic method for allergic rhinitis. The scientists studied nasal smears using a method originally developed for blood samples: With a recent development in biochip technology, practitioners have been able for some time now to measure antibody concentrations for 112 different allergens with a single small blood sample. This team used this molecular diagnostics technology to measure concentrations of immunoglobulin E (IgE) antibodies in the blood and nasal secretions of test subjects. These antibodies play a role in certain allergic responses. The researchers studied individuals with and without sensitization to the most common airborne allergens, including dust mite castings, grass pollen and the pollen of birch, hazelnut and alder trees. For the same tests, the blood and nasal smears yielded similar results: They detected identical allergic sensitization patterns, i.e. the same sets of substances for which the body had developed an immune response. This was the case for all airborne allergens investigated. Previous studies had already demonstrated a link between the detection of allergy antibodies in the blood and in nasal secretions for certain aeroallergens. The researchers have now confirmed this correlation for a wide range of such allergens.

SOURCE: Science Daily News, April 2020

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                               Evaluating grip strength to identify early diabetes

A new study reports valuable new grip strength metrics that provide healthcare practitioners with an easy-to-perform, time-efficient screening tool for type 2 diabetes (T2DM). Muscular weakness is known to be associated with T2DM in otherwise seemingly healthy adults, however previous research had not found a way to assess this reliably. The current study was able to identify consistent grip strength cut points relative to body weight, gender, and age group in a large nationally representative sample of participants pre-screened for comorbid conditions such as hypertension. T2DM is linked to increased cardiovascular-related morbidity and mortality. T2DM is asymptomatic in its initial stages, and a prompt diagnosis can prevent or delay vascular complications such as neuropathy, retinopathy and nephropathy. Researchers analyzed survey data from the 2011-2012 and 2013-2014 National Health and Nutrition Examination Survey to establish normalized grip strength (grip strength relative to body weight) cut points for T2DM risk. Inexpensive portable handgrip dynamometer devices were used to determine hand and forearm strength. After controlling for sociodemographic (i.e., race/ethnicity, education, poverty, sex, and age), lifestyle factors (i.e., sedentary behavior, alcohol use, and smoking status), and waist circumference, the investigators identified the grip strength levels of at-risk patients who were otherwise healthy. These levels are presented with age- and sex-specific grip strength cut points that correspond to varying body weights to increase the ease of use for practitioners as indicators of when further diabetes diagnostic testing is warranted. Researcher said that given the low cost, minimal training requirement and quickness of the assessment, the use of the normalized grip strength cut points in this paper could be used in routine health screenings to identify at-risk patients and improve diagnosis and outcomes.

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          Brain discovery suggests source of lifelong behavioral issues

Improper removal of faulty brain cells during neurodevelopment may cause lifelong behavioral issues, new research suggests. The finding also could have important implications for a wide range of neurodegenerative diseases, such as Alzheimer's and Parkinson's. Researcher have discovered that an unexpected form of cellular cleanup takes place in developing brains. If this process goes wrong happening too little or too much it can cause permanent changes in the brain's wiring. In lab mice, this results in anxiety-like behavior, and it may play a role in neurological conditions such as autism in humans. Brain cells to have genomic compromises. So this would be a normal mechanism to expel those cells from being incorporated into the central nervous system explained by researcher. When the damage isn't recognized, the cells that have DNA damage live on in the CNS and can be seen by accumulation of DNA damage in the brain. The cellular cleaner the researchers spotted, the AIM2 inflammasome, has been associated primarily with the body's immune response to infections but has not been extensively studied in the brain. But there it plays a critical role in ensuring the developing brain is assembled properly and functions correctly. More than half the neurons created during brain development end up dying, so proper cleanup is essential. Researcher said, for example, ataxia is a condition that causes people to lose control of their movements. There's a potential that this pathway could be contributing to the neuronal loss that is seen in ataxia. On the one hand, it can have negative consequences, like, potentially, ataxia. A lot of the early-onset neurodegenerative diseases are associated with mutations in DNA damage repair proteins, and this pathway could also be involved. The discovery came about somewhat serendipitously, the result of an observation of the behavior of lab mice while the researchers were investigating traumatic brain injury. But following that unexpected lead has given scientists a better understanding of brain development, and that understanding may one day yield new treatments for neurological diseases.

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