Genetic Explanation Research Articles

Teaching the Teachers the Genetics of Learning: An Application of the Mixed Blessings Model

AbstractDecades of educational genetics research have highlighted that differences in academic achievement are partly explained by genetic variation between individuals. Consequently, there is ongoing discussion about whether genetic influences on educationally related traits should be more widely acknowledged in schools and communicated specifically to teachers. Nonetheless, there is little research on how teachers might interpret such information, and how it might alter their perceptions of the students they teach or their teaching practice. In this review, we draw on the mixed blessings model proposed by Haslam and Kvaale, Current Directions in Psychological Science, 2015, 24, 399–404, as a framework for defining both positive and negative repercussions of disseminating the findings of educational genetic research to teachers. We discuss research examining teacher perceptions of student ability and behavior and findings outlining perceptions of psychological disorders when genetic explanations are invoked. We conclude by proposing new directions for research designed to better understand interpretations of genetic information in school contexts.

NETMAGE: A human disease phenotype map generator for the network-based visualization of phenome-wide association study results.

BackgroundDisease complications, the onset of secondary phenotypes given a primary condition, can exacerbate the long-term severity of outcomes. However, the exact cause of many of these cross-phenotype associations is still unknown. One potential reason is shared genetic etiology—common genetic drivers may lead to the onset of multiple phenotypes. Disease-disease networks (DDNs), where nodes represent diseases and edges represent associations between diseases, can provide an intuitive way of understanding the relationships between phenotypes. Using summary statistics from a phenome-wide association study (PheWAS), we can generate a corresponding DDN where edges represent shared genetic variants between diseases. Such a network can help us analyze genetic associations across the diseasome, the landscape of all human diseases, and identify potential genetic influences for disease complications.ResultsTo improve the ease of network-based analysis of shared genetic components across phenotypes, we developed the humaN disEase phenoType MAp GEnerator (NETMAGE), a web-based tool that produces interactive DDN visualizations from PheWAS summary statistics. Users can search the map by various attributes and select nodes to view related phenotypes, associated variants, and various network statistics. As a test case, we used NETMAGE to construct a network from UK BioBank (UKBB) PheWAS summary statistic data. Our map correctly displayed previously identified disease comorbidities from the UKBB and identified concentrations of hub diseases in the endocrine/metabolic and circulatory disease categories. By examining the associations between phenotypes in our map, we can identify potential genetic explanations for the relationships between diseases and better understand the underlying architecture of the human diseasome. Our tool thus provides researchers with a means to identify prospective genetic targets for drug design, using network medicine to contribute to the exploration of personalized medicine.

Bony deformities in a child with untreated osteogenesis imperfecta type III

Osteogenesis Imperfecta (OI) is a skeletal dysplasia that affects the cross-linking of Type 1 collagen leading to a wide spectrum of manifestations including bony abnormalities, scleral abnormalities, dentinogenesis imperfecta, and hearing abnormalities [1]. Orthopedic manifestations of OI include basilar invagination, kyphoscoliosis, codfish vertebrae, bowing deformities of the long bones, coxa vara, protrusion acetabuli, pathologic fractures, and radial head dislocations [1]. The Sillence Classification, originally designed to describe Types I – IV, has been expanded upon to includes Type V, VI, VII, which do not have a Type I collagen mutation, and instead have other genetic explanations (CRTAP, LEPRE1 genes) for the abnormal bone seen on microscopy [1,2]. Type I, IV represent milder forms of disease, Type V-VII represent milder forms of disease, Type III is the most severe survivable form, and Type II is lethal at birth [1,2]. We present a case of Sillence Type III OI, diagnosed by genetic analysis at birth, with significant bony deformities. She did not have appropriate multidisciplinary medical management of her condition and presented to our clinic at age 14. Radiographs of the spine and extremities demonstrated kyphoscoliosis, bilateral protrusio acetabuli, multiapical bowing bony deformities of femora, tibia, humeri, forearm, radial head dislocations, and short stature. This case highlights the importance of multidisciplinary management for children with OI. This includes physical rehabilitation [3], bisphosphonates [3,4] and more recently gene therapies [3,4], and stem cell transplantation therapies [4]. Patients with Osteogenesis Imperfecta Type III have a limited lifespan [5] and it is important to maximize the advantage of medical therapies. In the absence of the appropriate medical care, osteogenesis imperfecta can develop progressive deformities in the long bones, a high risk of fragility fractures, and progressive kyphoscoliosis that can be difficult to manage surgically due to underlying osteopenia.

Идеографический словарь архитектурно-дизайнерской терминологии русского языка

The article discusses reasons for compiling a dictionary of architectural and design terms in the Russian language. The topicality of creating it is connected with the brisk growth of design activity, the branching out of a new training program, Design of Architectural Environment, and the absence of a linguistic terminological dictionary of this professional sphere. The aim of the article is to describe the conception of an ideographic dictionary of Russian architectural and design terminology. The dictionary is based on the special language of architecture and design selected from terminological reference books, educational materials and research literature, commercial catalogues, professional weblogs, websites, and e-commerce sites. The dictionary defines not only terms, but also terminoids, preterms and quasi-terms, and pays special attention to the foreign terminological units and neologisms. This is caused by the under-investigated functional lexis of the architectural environment design sphere, variability and movability of its concepts and terms. The research methods and techniques used in the study are: the lexicographical method with the research techniques of thematic (ideographic) arrangement, definition, componential and contextual analyses. The chosen type of an ideographic dictionary defined its marco-structure: it is represented by a system of thematic groups, subgroups and microgroups, contributes to the development of a holistic professional worldview, and facilitates work with the dictionary. The microstructure shows the content of a lexical entry including core and optional components as well as its design. The core components include the headword with its variants, their stresses and pronunciation features, information on the word’s grammar, its definition and examples of its usage in professional speech. The optional components (etymology, derivatives, terminological collocations with the headword, analogues, synonyms and illustrations) are used as supplementary characteristics of a lexical item if available. Definitions are made by the principle of generic, genetic, operational and contextual explanations with elements of encyclopedic information. The dictionary is intended for linguists, terminologists, students and teachers of the disciplines of the Design of the Architectural Environment training programs, and is of interest to professionals in this field

Genetic Testing in Patients with High Lipoprotein(a): Experience from the UCSD Lipoprotein(a) Specialty Clinic†

Lead Author's Financial Disclosures Nothing to disclose. Study Funding None. Background/Synopsis Lipoprotein(a) (Lp(a)) is an inherited and likely causal risk factor for cardiovascular disease (CVD) and aortic stenosis. LPA variants rs10455872 and rs3798220 are present in ∼15% and ∼3% of Caucasians, respectively, and are associated with elevated Lp(a) levels. Genetic testing in clinical practice is emerging as a tool for personalizing risk assessment and treatment decisions [1-3]. Objective/Purpose To explore the role of genetic testing for LPA SNPs and other genetic mutations in patients with elevated Lp(a). Methods In the UC San Diego Lipoprotein(a) Specialty Clinic, next-generation DNA sequencing was performed using the GBinsight Comprehensive Dyslipidemia Panel (GB Lifesciences, San Diego, CA, USA) in 26 patients with Lp(a) ³ 50 mg/dL, evaluating 327 exons and selected single-nucleotide polymorphisms (SNPs) in 129 genes known or suspected to be associated with CVD. Known LPA SNPs and high impact variants in other genes associated with lipid abnormalities were reported as pathogenic/likely pathogenic. Given non-normality, Lp(a) values were compared using a Mann-Whitney U test. Results Among the 26 patients (mean age 61 yrs, 50% women), 14 (53.8%) had LPA SNPs that have been shown to be associated with elevated Lp(a): rs10455872 (minor allele frequency (MAF) 2.2%) occurred in 9 patients (34.6%), and rs3798220 (MAF 5.1%) occurred in 7 patients (26.9%). Two patients (7.7%) had both rs10455872 and rs3798220 LPA SNPs. LPA SNP rs41272112 (MAF 2.2%) was present in 1 patient (3.8%), and rs186696265 (MAF 0.3%) was present in 4 patients (15.4%). Thus, 12 patients (46.2%) with elevated Lp(a) had no known LPA SNPs. Three of those 12 patients had other potential genetic explanations for elevated Lp(a) (compound heterozygote LDLR, APOE e4 homozygote, and a heterozygous likely pathogenic variant in LDLRAP1) (Table). Patients with elevated Lp(a) and at least 1 LPA variant had Lp(a) 166 +/- 92 mg/dL (mean+/-SD) (131.5, 106.75-243 mg/dL (median, IQR)), and those with elevated Lp(a) but without an LPA variant had Lp(a) 105.9 +/- 46 mg/dL (mean+/-SD) (100.5, 65.5-127.25 mg/dL (median, IQR) (p=0.08)). Conclusions Real-world testing for LPA SNPs in a referral Lp(a) specialty practice demonstrates genetic associations of elevated Lp(a) in approximately half of the patients, which is substantially higher than the general population. However, a significant proportion of patients have no known LPA SNPs despite highly elevated Lp(a), suggesting they harbor small apo(a) isoforms. The role of genetic testing at the bedside in such patients is evolving. A dedicated Lp(a) specialty clinic may allow optimal evaluation and management of patients with elevated Lp(a). Nothing to disclose.

Wille und Erkenntnis: Synthese, Dualismus oder Aporie? Ein konzeptionelles Grundproblem der Philosophie Schopenhauers

The relationship between will and cognition represents one of the most fundamental issues in Schopenhauer’s philosophy. The possibility of aesthetic experience, which involves a deliverance of cognition from the service of the will, and even more so the doctrine of the redemption through cognition – the fact that cognition can become a “tranquillizer” of the will and bring will to abolish itself – seems incompatible with Schopenhauer’s voluntaristic metaphysics (i.e., with the principle of the “primacy of the will”). This paper aims to analyse this controversial part of Schopenhauer’s discourse, especially in its implications for the system’s logical consistency, and tries to provide a theoretical and genetic explanation of the question.

Forward and reverse genetic dissection of morphogenesis identifies filament-competent Candida auris strains

Candida auris is an emerging healthcare-associated pathogen of global concern. Recent reports have identified C. auris isolates that grow in cellular aggregates or filaments, often without a clear genetic explanation. To investigate the regulation of C. auris morphogenesis, we applied an Agrobacterium-mediated transformation system to all four C. auris clades. We identified aggregating mutants associated with disruption of chitin regulation, while disruption of ELM1 produced a polarized, filamentous growth morphology. We developed a transiently expressed Cas9 and sgRNA system for C. auris that significantly increased targeted transformation efficiency across the four C. auris clades. Using this system, we confirmed the roles of C. auris morphogenesis regulators. Morphogenic mutants showed dysregulated chitinase expression, attenuated virulence, and altered antifungal susceptibility. Our findings provide insights into the genetic regulation of aggregating and filamentous morphogenesis in C. auris. Furthermore, the genetic tools described here will allow for efficient manipulation of the C. auris genome.

Detection and Estimation of Genetic and Environmental Parameters through Model Fitting of Ten Bulb Yield Contributing Traits in Onion

Two onion varieties P2 and P3 and their products F1 and F2 were evaluated in summer and winter seasons for this investigation. Estimated mean values of different traits showed variations from generation to generation in each season. Values of six-parameters viz., m ̂, [d], [h], e1, gd1, gh1 for all the characters were significant except gd1 for a number of leaves, leaf length and bulb volume and also [d] for leaf length and neck length. Overall means ‘m ̂’ had the highest magnitude than [d], [h], e1, gd1 and gh1 for all the characters. Environmental parameter ‘e1’ also exhibited higher magnitude than [d], gd1 and gh1. As the values of [d] and gd1 were found to be non-significant, 4-parameter model was considered for leaf length only. Five-parameter model was considered for neck length, number of leaves and bulb volume and for rest of the traits 6-parameter model was considered. The goodness of fit test showed that 4, 5 and 6-parameter models were not adequate except bulb length and neck length. Therefore, for the development of these two traits in consideration of genotype × environment (G × E) interaction proper design and analysis needs to be done. Due to significant 2 values for other characters the situations becoming more complex as G × E interaction model is inadequate, so for their exact genetic explanation G × E model needs to be extended to include linkage and non-allelic parameters.

Visions of lexicography of a semantic European

Abstract In this essay, it is assumed that the languages of Latin Europe do have many semantic features in common, which contradicts the prevailing view of a general semantic particularity of every individual language and thus the exploitation for national-political purposes arising from that view. However, the proposition made here requires a summary and the assessment of different semantic concepts led by the idea of commonality. By means of individual cases that can be understood as relevant examples, a vision of lexicography will follow that aims at replacing the biologistic concept of a genetic explanation for contrastive semantics by the concept of a comparative semantics that is based on socio-historical, cultural-historcial and textual-historical arguments. In doing so, a historiography relating to the subject-matter of “semantics” will be suggested that assigns a semantic bridging function to Late Antiquity / Early Medieval Latin in relation to all languages of Latin Europe. The logic of the argument implies that a new era of semantic history begins upon the development of a structure of national languages in Europe, whose historical basis can still be recognised in the semantic communalities.

Idealisation, genetic explanations and political behaviours: Notes on the anti-reductionist critique of genopolitics

The rapid development of genetic research, determined, among others, by the requirements of The Human Genome Project, and a gradual reorientation in the perception of the role of nature and culture in the process of shaping complex networks of human relations by some political scientists, result in the increasing application of genetic data and methods in research regarding political behaviours. One of the key philosophical objections against the studies of the genetic foundations of political behaviours is that of excessive reductionism. This is supposed to manifest itself in the inadequate selection of the level of analysis for the explained phenomenon, the incompleteness of explanations and their low utility. My findings show that this objection is not sufficiently supported by contemporary science. Both studies using classical behavioural genetic methodologies and studies using DNA-based methods show that genes most likely play a role in political behaviours. Emphasising the significance of genetic influences in the midst of multiple extra-genetic interactions generates highly idealised explanations. Using the conceptual apparatus of the deformational concept of culture, I have demonstrated that the omission of a number of important extra-genetic influences by researchers is a consequence of focusing on specific causal patterns. This omission, however, does not entail negating the influence of non-genetic factors and, importantly, it may not have to be permanent. Following this approach, if correct, the reductionism of research into the genetic foundations of political behaviours is a standard cognitive procedure applied in science.

Dextral to sinistral coiling switch in planktic foraminifer Morozovella during the Early Eocene Climatic Optimum

Coiling direction is a basic characteristic of trochospiral planktic foraminifera. Modifications in the coiling direction within ancient planktic foraminiferal populations may reflect important changes in evolution or environment, yet they remain scarcely discussed. Here we investigate fluctuations in the coiling direction within Morozovella assemblages from sections that span the interval of peak Cenozoic warmth, the Early Eocene Climatic Optimum (EECO; ~53–49 million years ago, Ma), at Atlantic Ocean Drilling Program (ODP) sites 1051, 1258 and 1263. The surface-dwelling genus Morozovella is of particular interest because it dominated tropical-subtropical early Paleogene assemblages then suffered an abrupt and permanent decline in abundance and taxonomic diversity at the start of the EECO. At all ODP sites, morozovellids display a dominant dextral coiling preference during the interval preceding the EECO. However, all the Morozovella species at all sites modify their coiling from preferentially dextral to sinistral coiling within the EECO, <200 kyr after the K/X event (~52.8 Ma), providing a new biostratigraphic tool for correlation. We also document that before the major shift in morozovellid coiling, transient excursions to higher abundances of sinistral tests occurred in conjunction with negative carbon isotope excursions. Significantly, carbon isotope data reveal that sinistral morphotypes belonging to the same morphospecies typically have lower δ 13 C values. The dominance of sinistral morphotypes, at the expense of dextral forms within the EECO, coupled with the lower δ 13 C signatures of the former, suggests that the sinistral forms were less dependent on their photosymbiotic partnerships and thus able to adapt more readily to paleoceanographic change at the EECO. The observed sinistral and dextral coiling of morozovellids can be a genetically heritable characteristic that lies within cryptic speciation across multiple morphologically defined species. Alternatively the coiling changes were exclusively ecophenotypic responses whereby different species were able to preferentially adopt sinistral coiling in reaction to the changed conditions in the mixed-layer during the EECO. Previous interpretations of coiling flips in planktic foraminifera in the early Eocene, especially including morozovellids, have favoured a genetic explanation rather than an ecological response. Our present data cannot validate or disprove this idea, but should stimulate renewed thought on the matter. • Coiling data on Morozovella species are presented from three widely separated Atlantic Ocean Drilling Program sites. • Morozovella switch from dextral to sinistral coiling direction across the Early Eocene Climatic Optimum. • Changes in coiling direction occurred in multiple morphologically distinct species. • Carbon isotopes indicate dextral and sinistral morphotypes differ in their ecology. • Sinistral morphotypes were less dependent on photosymbiosis and thus able to adapt more readily to paleoceanographic change.

Bi-allelic variants in DNAH10 cause asthenoteratozoospermia and male infertility.

Multiple morphological abnormalities in the sperm flagella (MMAF) comprise a severe phenotype of asthenoteratozoospermia with reduced or absent spermatozoa motility. Whereas dozens of candidate pathogenic genes for MMAF have been identified, the genetic cause in a large proportion of patients is unknown. We attempted to identify novel genetic explanations for MMAF. We performed whole-exome sequencing of patients with MMAF to identify pathogenic variants. The phenotypes of spermatozoa in patients carrying DNAH10 variants were investigated using haematoxylin and eosin staining, scanning electron microscopy, and transmission electron microscopy. The expression and location of DNAH10 and other spermatozoa structure-related proteins were analyzed using immunofluorescence assays. We found one homozygous frameshift DNAH10 variant (NM_207437: c.2514delG:p.L839*) and one compound heterozygous DNAH10 variant (NM_207437: c.10820T > C:p.M3607T; c.12692C > T:p.T4231I) in two patients with MMAF. These variants were absent or rare in the general population. Haematoxylin and eosin staining and scanning electron microscopy revealed the significant disruption of sperm flagella in the patients. In addition, ultrastructural analysis by transmission electron microscopy showed significant inner dynein arm (IDA) deficiency in sperm flagella. Using immunofluorescence assays, we found a significant reduction in IDA-related proteins including DNAH10 and DNAH1. We identified putative novel pathogenic variants in DNAH10 for MMAF, which might advance the genetic diagnosis and clinical genetic counselling for male infertility.

ISPG ETHICS COMMITTEE SYMPOSIUM: RACE AND STRUCTURAL RACISM IN PSYCHIATRY AND PSYCHIATRIC GENETICS

Introduction: Advances in genomics research have raised several ethical concerns. One concern is the potential impact of genomics research on stigma experienced by people affected by a disease. Studies have found that the type of illness as well as disease causal beliefs impact on the relation between genetic attribution and stigma. This study explored the potential impact of genetic attribution of disease on stigma among Xhosa people with Rheumatic Heart Disease (RHD). Methods: Study participants were 46 Xhosa people with RHD living in the Western Cape Province of South Africa. Using video vignettes in 7 focus group discussions we explored whether and how genetic attribution may impact on disease-stigma. Vignettes introduced participants to non-genetic and genetic causal explanations and were followed-up with a series of open-ended questions eliciting their perceptions of non-genetic disease causes as well as genetic causation and its impact on internalised stigma. Results: This study found that Xhosa people with RHD have a general understanding of genetics and genetic attribution for disease. Additionally, and not withstanding their genetic knowledge, these participants hold multiple disease causal beliefs including genetic, infectious disease, psychosocial, behavioural and cultural explanations. While there was evidence of internalised stigma experiences among participants, these appeared not to be related to a genetic attribution to the disease. Discussion: The findings of this study provide clues as to why it is unlikely that a genetic conceptualisation of disease impacts internalised stigma experiences of Xhosa people. The causal explanations provided by participants reflect their cultural understandings and their context, namely, living in low-income and poverty-stricken environments. Divergence in these findings from much of the evidence from high-income countries emphasises that context matters when considering the impact of genetic attribution on stigma and caution against generalising findings from one part of the globe to another.

Comparison of the Effects of a Genetic, a Mild Encephalitis, and a Psychosocial Causal Explanation of Schizophrenia on Stigmatizing Attitudes - a Pilot Study With a Quasi-Experimental Design.

Background: Previous research has shown that the endorsement of biogenetic causal explanations of schizophrenia is associated with stronger stigmatizing attitudes against people with schizophrenia than the endorsement of psychosocial explanations. However, little is known about whether different biogenetic causal explanation beliefs differentially affect stigmatizing attitudes. This is particularly valid for the endorsement of the mild encephalitis hypothesis of schizophrenia.Aim: To examine to what extent different causal explanations of schizophrenia influence the desire for social distance from persons with schizophrenia.Methods: A study with a prospective, quasi-experimental design was carried out with students in Germany (N = 333). A case vignette depicting a person with schizophrenia-typical symptoms was presented, and a social distance scale (SDS) was used to measure the stigmatizing attitude against the person described. Participants were randomly assigned to one of three groups receiving different causal explanations of schizophrenia (genetic, mild encephalitis hypothesis, or psychosocial) without treatment information.Results: A one-way ANOVA showed that the mean SDS was lowest in the group with the mild encephalitis hypothesis explanation, followed by the genetic explanation group, and highest in the psychosocial explanation group. However, the differences between the groups were small and not significant. A subanalysis revealed a significant interaction between gender and causal explanation. Women showed a significantly lower desire for social distance than men when receiving the mild encephalitis hypothesis. Neither the study discipline nor the number of semesters of study had significant effects on the mean SDS. The differences between the mean SDS scores for the different items were much bigger than the differences for the different causal explanations. Regardless of the causal explanation, the extent of the desired social distance depends strongly on social proximity.Conclusion: The present study fits into previous research, which has found that biogenetic beliefs were either associated with more social distance or did not yield a statistically significant association. Although we found a small gender-specific effect of the endorsement of the mild encephalitis hypothesis, we do not recommend gender-specific anti-stigmatization campaigns because they might rightly raise suspicions of dishonesty and manipulation. Rather we support recovery-oriented messages focusing on effective treatments.

Синдром Кальмана у монозиготных близнецов как изолированное проявление дефекта гена SOX10

More than 30 genes are known to take part in hypothalamic-pituitary-gonadal axis development at the date and role of more than 10 other genes is studied. Despite it about 50% of isolated hypogonadotropic hypogonadism cases still have no molecular genetic explanation. A number of specific associations between iHH and different not-reproductive manifestations called syndromic forms are distinguished in general group of iHH. For example, the combination of Kalmann syndrome with sensorineural hearing loss is known as manifestation for defects of some genes encoding factors of neuronal migration; in patients with this phenotype CHD7 , SOX10 genes defects are most frequent. However, defects in the genes of neuronal migration factors are characterized by a wide variability of phenotype, which is explained by the epigenetic mechanisms influence. Carriers of the mutation within the same family may lack some non-reproductive manifestations as well as hypogonadism. Here we present a case of Kalmann syndrome in monozygous twins, caused by a previously not described heterozygous mutation c.462C> G: p.I154M in the SOX10 gene in the absence of sensorineural hearing loss. The mutation was inherited from a father who has only isolated anosmia in the phenotype. This mutation was identified during full exome sequencing. This unique observation for Russia shows on the one hand expediency to check SOX10 sequence in addition to the other factors of neuronal migration and differentiation and, on the other hand, the prospect of full exome sequencing in a group of patients with undifferentiated iHH.

The link between attention deficit hyperactivity disorder (ADHD) symptoms and obesity-related traits: genetic and prenatal explanations

Attention-deficit/hyperactivity disorder (ADHD) often co-occurs with obesity, however, the potential causality between the traits remains unclear. We examined both genetic and prenatal evidence for causality using Mendelian Randomisation (MR) and polygenic risk scores (PRS). We conducted bi-directional MR on ADHD liability and six obesity-related traits using summary statistics from the largest available meta-analyses of genome-wide association studies. We also examined the shared genetic aetiology between ADHD symptoms (inattention and hyperactivity) and body mass index (BMI) by PRS association analysis using longitudinal data from Northern Finland Birth Cohort 1986 (NFBC1986, n = 2984). Lastly, we examined the impact of the prenatal environment by association analysis of maternal pre-pregnancy BMI and offspring ADHD symptoms, adjusted for PRS of both traits, in NFBC1986 dataset. Through MR analyses, we found evidence for bidirectional causality between ADHD liability and obesity-related traits. PRS association analyses showed evidence for genetic overlap between ADHD symptoms and BMI. We found no evidence for a difference between inattention and hyperactivity symptoms, suggesting that neither symptom subtype is driving the association. We found evidence for association between maternal pre-pregnancy BMI and offspring ADHD symptoms after adjusting for both BMI and ADHD PRS (association p-value = 0.027 for inattention, p = 0.008 for hyperactivity). These results are consistent with the hypothesis that the co-occurrence between ADHD and obesity has both genetic and prenatal environmental origins.

WHOLE EXOME SEQUENCING IDENTIFIES A RARE NONSENSE MUTATION IN NACAD AS A POSSIBLE CAUSE OF COVID ORCHITIS IN BROTHERS

This project sought to uncover genetic explanations as to why certain men face increased susceptibility to developing COVID orchitis. Our goal was to identify genetic variants associated with COVID orchitis in a group of patients, aided by whole-exome sequencing and protein phenotyping of affected patients.

Premenstrual syndrome mechanism in the brain

Premenstrual syndrome (PMS) is a disorder in which a set of physical, emotional, and behavioral symptoms, mostly seen in the late luteal phase of the menstrual cycle, disappear with the onset of menstruation. It has a high incidence in society, and it causes problems in a person's daily life. Premenstrual dysphoric disorder is diagnosed when symptoms are clinically or socially more severe. Although the exact cause of these disorders is unknown, numerous theories have been proposed, including gonadal hormones, neurotransmitters, central nervous system (CNS) abnormalities, diet, genetic factors, and environmental factors. In this study, current studies on premenstrual disorders and the brain were compiled to shed light on the etiology of PMS. In the light of the literature, a summary of recent studies on the role of neurotransmitters related to PMS, functioning in the CNS, hormonal changes, gray matter, brain resting state, abnormalities in the limbic system, emotion processing and regulation, genetic explanations, nutrition, and alternative medicine has been presented.

Genetic errors of immunity distinguish pediatric nonmalignant lymphoproliferative disorders

Pediatric nonmalignant lymphoproliferative disorders (PLPDs) are clinically and genetically heterogeneous. Long-standing immune dysregulation and lymphoproliferation in children may be life-threatening, and a paucity of data exists to guide evaluation and treatment of children with PLPD. The primary objective of this study was to ascertain the spectrum of genomic immunologic defects in PLPD. Secondary objectives included characterization of clinical outcomes and associations between genetic diagnoses and those outcomes. PLPD was defined by persistent lymphadenopathy, lymph organ involvement, or lymphocytic infiltration for more than 3 months, with or without chronic or significant Epstein-Barr virus (EBV) infection. Fifty-one subjects from 47 different families with PLPD were analyzed using whole exome sequencing. Whole exome sequencing identified likely genetic errors of immunity in 51% to 62% of families (53% to 65% of affected children). Presence of a genetic etiology was associated with younger age and hemophagocytic lymphohistiocytosis. Ten-year survival for the cohort was 72.4%, and patients with viable genetic diagnoses had a higher survival rate (82%) compared to children without a genetic explanation (48%, P= .03). Survival outcomes for individuals with EBV-associated disease and no genetic explanation were particularly worse than outcomes for subjects with EBV-associated disease and a genetic explanation (17% vs 90%; P= .002). Ascertainment of a molecular diagnosis provided targetable treatment options for up to 18 individuals and led to active management changes for 12 patients. PLPD defines children at high risk for mortality, and whole exome sequencing informs clinical risks and therapeutic opportunities for this diagnosis.

Impact of diagnostic labels and causal explanations for weight gain on diet intentions, cognitions and emotions: An experimental online study

Disease labels and causal explanations for certain symptoms or conditions have been found to have both positive and negative outcomes. For example, a diagnosis of polycystic ovary syndrome could conceivably motivate a person to engage in weight management, which is the recommended first line treatment. Furthermore, doctors may feel more comfortable discussing weight when linked to a medical condition. However, such a diagnosis may elicit feelings of increased anxiety, perceived severity and reduced sense of control. Mixed findings are also evident for impacts of genetic explanations on psychosocial outcomes and behaviours. Using hypothetical scenarios presented in an online survey, participants were asked to imagine that they were visiting their general practitioner due to experiencing weight gain, irregular periods, and more pimples than usual. Participants were randomised to receive different diagnostic labels (‘polycystic ovary syndrome', ‘weight’ or no label/description) and causal explanations (genetic or environmental) for their symptoms. Primary outcomes assessed included intention to eat a healthier diet and perceived personal control of weight (average score on scale 1–7 across 3 items). Secondary outcomes included weight stigma, blameworthiness, worry, perceived severity, self-esteem, belief diet will reduce risks and menu item choice. Participants were 545 females aged 18–45 years (mean = 33 years), living in Australia, recruited through a national online recruitment panel. The sample was overweight on average (BMI = 26.5). Participants reporting a PCOS diagnosis were excluded from analyses. We found no main effects of the label or explanation on intention to eat healthier or perceived personal control of weight. For secondary outcomes, those given the genetic explanation reported higher weight stigma (range 1–7; MD = 0.27, 95%CI: 0.011,0.522), greater worry (range 1–7; MD = 0.27, 95%CI: 0.037,0.496), lower self-esteem (range 10–40; MD = 1.26, 95%CI: 0.28 to 2.24) and perceived their weight as more severe (range 1–7; MD = 0.28; 95%CI: 0.05,0.52) than those given the environmental explanation, averaged over disease label given. These findings further highlight the deleterious effects of genetic explanations on psychosocial outcomes and reinforce the need for caution when communicating the aetiology of weight-related health issues.