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Objectives: Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease with an unsatisfactory state of treatment. We aim to explore novel targets for SLE from a genetic standpoint. Methods: Cis-expression quantitative trait loci (eQTLs) for whole blood from 31,684 samples provided by the eQTLGen Consortium as well as two large SLE cohorts were utilized for screening and validating genes causally associated with SLE. Colocalization analysis was employed to further investigate whether changes in the expression of risk genes, as indicated by GWAS signals, influence the occurrence and development of SLE. Targets identified for drug development were evaluated for potential side effects using a phenome-wide association study (PheWAS). Based on the multiple databases, we explored the interactions between drugs and genes for drug prediction and the assessment of current medications. Results: The analysis comprised 5427 druggable genes in total. The two-sample Mendelian randomization (MR) in the discovery phase identified 20 genes causally associated with SLE and validated 8 genes in the replication phase. Colocalization analysis ultimately identified five genes (BLK, HIST1H3H, HSPA1A, IL12A, NEU1) with PPH4 > 0.8. PheWAS further indicated that drugs acting on BLK and IL12A are less likely to have potential side effects, while HSPA1A and NEU1 were associated with other traits. Four genes (BLK, HSPA1A, IL12A, NEU1) have been targeted for drug development in autoimmune diseases and other conditions. Conclusions:.This study identified five genes as therapeutic targets for SLE. Repurposing and developing drugs targeting these genes is anticipated to improve the existing treatment state for SLE. Key Points • We identified five gene targets of priority for the treatment of SLE, with BLK and IL12A indicating fewer side effects. • Among the existing drugs that target these candidate genes, Ustekinumab, Ebdarokimab, and Briakinumab (targeting the IL12 gene) and CD24FC (targeting HSPA1A) may potentially be repurposed for the treatment of SLE. [ABSTRACT FROM AUTHOR]

Infections with the coronavirus disease 2019 (COVID-19) and disorders of the heart and blood vessels are causally related. To ascertain the causal relationship between COVID-19 and cardiovascular disease (CVD), we carried out a Mendelian randomization (MR) study through a method known as inverse variance weighting (IVW). When analyzing multiple SNPs, MR can meta-aggregate the effects of multiple loci by using IVW meta-pooling method. The weighted median (WM) is the median of the distribution function obtained by ranking all individual SNP effect values according to their weights. WM yields robust estimates when at least 50% of the information originates from valid instrumental variables (IVs). Directed gene pleiotropy in the included IVs is permitted because MR-Egger does not require a regression straight line through the origin. For MR estimation, IVW, WM and MR-Egger were employed. Sensitivity analysis was conducted using funnel plots, Cochran's Q test, MR-Egger intercept test, MR-PRESSO, and leave-one-out analysis. SNPs related to exposure to COVID-19 and CVD were compiled. CVD for COVID-19 infection, COVID-19 laboratory/self-reported negative, and other very severe respiratory diagnosis and population were randomly assigned using MR. The COVID-19 laboratory/self-reported negative results and other very severe respiratory confirmed cases versus MR analysis of CVD in the population (p > 0.05); COVID-19 infection to CVD (p = 0.033, OR = 1.001, 95%Ci: 1.000-1.001); and the MR-Egger results indicated that COVID-19 infection was associated with CVD risk. This MR study provides preliminary evidence for the validity of the causal link between COVID-19 infection and CVD. [ABSTRACT FROM AUTHOR]

This article offers a close examination of a small selection of pedigrees taken from German Mendelian and eugenic scholarship of the 1920s and 1930s. It examines the procedures that became customary for presenting data on human inherited pathologies, as well as the frequent changes in the information content of those charts. Relevant biographical and genealogical data was removed, and important indications regarding the diagnostic methods applied by the investigating scholar were lost, as soon as a pedigree was charted or reproduced. Data on healthy individuals was condensed, leading to an emphasis on the hereditary burden of pathological traits. At times, healthy individuals were entirely omitted, as were exogenous martial partners. These modifications paved the way for further theoretical amendments, including the addition of 'carrier' status to chosen individuals along the pedigree. With this addition, these pedigrees changed their ontological status, from empirical records of human reproduction to partially hypothetical illustrations of Mendelian theory itself. This process was complemented by the representation of theoretical genetic models in the format of a human pedigree. A comparison to practices of charting pedigrees still common today suggests that the processes hereby revealed are far from exceptional. In line with the ideas put forward by Ludwik Fleck, they are interpreted as germane to the way scientific ideas are communicated and propagated and to the scientific culture of genetics. The article also offers a refinement to Fleck's analysis of textbook construction, which highlights the extent to which textbook examples differ from the original data on which they are based. [ABSTRACT FROM AUTHOR]

Background: Previous observational studies have discovered a connection between depression and mineral status. Confirming this potential connection is challenging due to confounding factors and potential reverse causality which is inherent in observational studies. Materials and Methods: We performed a Mendelian randomization (MR) analysis to estimate the causal association of serum minerals with depression. Leveraging summary-level data on depression, a genome-wide association study (GWAS) was applied. The data on serum minerals were collected from the FinnGen Biobank database. MR assessments representing causality were produced by inverse-variance weighted approaches with multiplicative random and fixed effects. Result: Sensitivity analyses were performed to validate the reliability of the results. A noteworthy correlation emerged between serum zinc levels and reduced risk of depression. An odds ratio (OR) of 0.917 for depression associated with a one standard deviation increase in serum zinc levels (OR = 0.968; 95% CI = 0.953-0.984, p = 1.19 x 10-4, random effects model inverse variance weighted (IVW)); (OR = 0.928; 95% CI = 0.634-1.358, p = 0.766, MR Egger). Sensitivity assessments supported this causation. However, the risk of depression did not exhibit an association with other minerals. Conclusions: In summary, a higher zinc concentration is causally associated with a reduced depression risk. This MR outcome may assist clinicians in the regulation of specific mineral intake, particularly for high-risk patients with serum zinc deficiencies. [ABSTRACT FROM AUTHOR]

The direction of research in population genetics theory is currently, and correctly, retrospective, that is directed toward the past. What events in the past have led to the presently observed genetic constitution of a population? This direction is inspired, first, by the large volumes of genomic data now available and, second, by the success of the classical prospective theory in validating the Darwinian theory in terms of Mendelian genetics. However, the prospective theory should not be forgotten, and in that theory, perhaps the most interesting and certainly the most controversial, is Fisher's so-called "Fundamental Theorem of Natural Selection." This article describes the history and the current status of that theorem. [ABSTRACT FROM AUTHOR]

This article explores the history and significance of the discovery of DNA's molecular structure by James D. Watson and Francis H. C. Crick in 1953. It emphasizes the importance of DNA replication, its specificity as genetic material, its informative capability, and its adaptability for mutation. The contributions of other scientists, such as Rosalind E. Franklin, Maurice H. F. Wilkins, and Edward Zacharias, are also acknowledged. The article concludes by discussing the impact of DNA discovery on various fields, including medicine and the fight against the COVID-19 pandemic. Additionally, it mentions earlier research by Hermann J. Muller, Theophilus S. Painter, and Theodosius G. Dobzhansky that provided evidence for the chromosome theory of inheritance and the discovery that DNA, rather than proteins, contains genetic material composed of nucleic acid. The discovery of DNA has revolutionized our understanding of genetics and has the potential to improve diagnosis, treatment strategies, and personalized approaches to diseases such as Alzheimer's and Parkinson's. [Extracted from the article]

Background: Serious games (SGs) have emerged as promising tools for life science education, providing interactive learning experiences that bolster accessibility and engagement. In the context of genetics education, which emphasizes hands-on problem-solving, SGs offer a potential platform to augment learning. Aim: This article presents the detailed design of a new educational SG, titled Punnett Farms, along with a pilot evaluation of the game. Designed to help students learn the fundamentals of Mendelian/molecular genetics, the game offers a colorful virtual world with embedded educational content aimed at cultivating interactive learning and engagement. Methods: Development of Punnett Farms was guided by principles of educational game design models. The game was implemented in Unity and C#. A pilot study was conducted with community college students (n = 22) to assess the game's strengths and areas for improvement. Pre-/post-intervention knowledge assessments, along with questionnaires inspired by the GEM and MEEGA+ frameworks, were used to obtain insights into participants' interest, enjoyment, and short-term learning outcomes. Results: Participants exhibited possible short-term knowledge gains after playing Punnett Farms, as reflected by improved quiz scores. In questionnaire responses, participants also reported improved content understanding, interest towards the subject, and overall enjoyment in learning genetics. Additionally, players rated the game highly for presentation and educational utility. Conclusion: By integrating educational game design principles, Punnett Farms aims to provide an immersive environment that supports learning of essential Mendelian genetics topics. Results from the pilot study were positive, suggesting the game has potential to be a helpful resource for genetics learners. Future efforts will focus on continuing to improve and evaluate the game across different contexts. [ABSTRACT FROM AUTHOR]

The article "Massification and Networking" by Vilém Flusser explores the impact of the information revolution on public and private spaces. Flusser argues that the flow of information has disrupted public space and blurred the boundaries of private spaces. He suggests that society has become passive consumers of information and proposes the idea of networking to make people active producers of information. However, he raises concerns about the concept of competence and the absurdity of cultural engagement. This document is a brief reflection on post-political ideas and may be of interest to researchers studying post-political theories. [Extracted from the article]

STUDY QUESTION Is there a causal relationship between 25-hydroxyvitamin D (25OHD) and miscarriage? SUMMARY ANSWER In this study, little evidence of a causal relationship was found between low serum 25OHD concentration or vitamin D deficiency and the risk of miscarriages. WHAT IS KNOWN ALREADY Associations between low vitamin D levels and increased risk of miscarriage have been reported, but causality is unclear. STUDY DESIGN, SIZE, DURATION The latest and largest genome-wide association studies (GWAS) for serum 25OHD concentration (n = 417 580), vitamin D deficiency (426 cases and 354 812 controls), miscarriage (16 906 cases and 149 622 controls), and the number of miscarriages (n = 78 700) were used to explore the causal association between serum vitamin D levels and miscarriage by two-sample Mendelian randomization analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS This study was based on summary GWAS results from the FinnGen database and the UK Biobank. The random-effect inverse-variance weighted method was regarded as the primary analysis; MR-Egger, weighted median, weighted mode, simple mode, and MR-pleiotropy residual sum and outlier (MR-PRESSO) were further employed as complementary methods. MR-Egger intercept analysis and MR-PRESSO were employed to test pleiotropy, and Cochran's Q statistic and leave-one-out sensitivity analysis were used to determine the heterogeneity and robustness of the overall estimates, respectively. MAIN RESULTS AND THE ROLE OF CHANCE There was insufficient evidence of causal associations between serum 25OHD concentration and miscarriage (odds ratio (OR) = 0.995, 95% CI: 0.888 to 1.114, P  = 0.927), or the number of miscarriages (β = –0.004, 95% CI: –0.040 to 0.032, P  = 0.829). Furthermore, little evidence of causality between genetically determined vitamin D deficiency to miscarriage (OR = 0.993, 95% CI: 0.966 to 1.021, P  = 0.624), or the number of miscarriages (β = 0.001, 95% CI: −0.009 to 0.011, P  = 0.828), was observed. The results of the sensitivity analysis were robust, and no significant heterogeneity or horizontal pleiotropy was found. LIMITATIONS, REASONS FOR CAUTION This study is limited by the absence of female-specific GWAS data and the limited amount of GWAS data available for this study, as well as the need for caution in generalizing the findings to non-European ethnic groups. WIDER IMPLICATIONS OF THE FINDINGS These findings enhance the current understanding of the intricate association between vitamin D and pregnancy outcomes, challenging prevailing beliefs regarding the strong association with miscarriage. The results provide a special perspective that may prompt further exploration and potentially offer insights for guiding future research and informing clinical guidelines pertaining to the management of miscarriage. STUDY FUNDING/COMPETING INTEREST(S) This project was supported by the Hubei Provincial Natural Science Foundation Program General Surface Project (2022CFB200), the Key Research & Developmental Program of of Hubei Province (2022BCA042), the Fundamental Research Funds for the Central Universities (2042022gf0007, 2042022kf1210), and the Interdisciplinary Innovative Talents Foundation from Renmin Hospital of Wuhan University (JCRCWL-2022-001, JCRCYG-2022-009). All authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

Cultivated eggplant (Solanum melongena L.) is produced in many countries with temperate and tropical climates and has great economic importance. In recent years, resistance to biotic and abiotic stress conditions in addition to increasing yield and quality has gained importance in plant breeding including eggplant breeding. Therefore, the wild relative S. incanum is an important parent in breeding studies as it provides resistance to some important biotic and abiotic stresses for eggplant. It is possible to obtain a fully fertile hybrid between the two species, as well as to establish F2 lines. However, it is a mystery whether there is gene introgression from wild ancestor in F2 individuals. The phenotypic distinguishing and elimination in selection of the nonhybrid plants by classical breeding methods requires a long time and intensive labour. For this reason, there is a need for solutions in breeding studies in which gene transfers from wild relatives can be detected in the early development stages of plants. In this study, it was aimed to determine whether the F2 individuals obtained from interspecific cross of an inbred line P45 belonging to S. melongena x S. incanum crosses, when they were at the seedling stage, were S. melongena, S. incanum or carry genes from both ancestors by using T1480 COSII marker. Among a total of 94 F2 eggplant individuals and two parent eggplant species, it was determined that 51 individuals carried DNA fragments from both parental eggplant species, while 22 individuals belonging to the S. incanum species and 23 individuals belonging to the S. melongena species were identified. The resulting segregation ratio was 1:2:1, which was in accordance with Mendelian genetics. The results clearly showed that T1480 could be a useful marker for distinguishing whether seedling stage F2 plants carry genes from S. melongena, S. incanum, or both parents. As a conclusion, T1480 COSII marker can be used in eggplant breeding studies and will enable the plant improvement to progress more reliably than classical approaches. [ABSTRACT FROM AUTHOR]

The article discusses the battle between the "biometricians" led by W.F.R. Weldon and the "Mendelian" allies led by William Bateson in England in the early 1900s. The author, Gregory Radick, argues that Weldon's untimely death prevented his case from being fully made, but his theory could have had a significant impact on the future of genetics. Radick explores the similarities and differences between Weldon and Bateson's theories, highlighting Weldon's emphasis on complex interactions of hereditary factors with the environment and developmental processes. The article also discusses the counterfactual scenario of what might have happened if Weldon's theory had prevailed over Mendelism, suggesting that it could have led to a different understanding of genetics without genetic determinism. However, the counterfactual story is met with objections, including the empirical distinguishability of the theories and the potential for other responses to Mendelism. The article concludes by acknowledging the need to correct misconceptions about genetic determinism and genes for traits, but questions the value of rehabilitating Weldon's theory or re-fighting the dispute with Bateson. [Extracted from the article]

In order to investigate the effect of FecB on litter size and growth and development traits of Suhu meat sheep and the inheritance patterns of FecB between parents and offspring in the population. In this experiment, 2241 sheep from the Suhu meat sheep population were tested for FecB using capillary electrophoresis. We combined the lambing records of 473 ewes, the growth trait records of 881 sheep at both the birth and weaning (2-month-old) stages, and the complete genealogical records of 643 lambs to analysis the distribution of FecB in the Suhu meat sheep breeding population, its effect on litter size of ewes, growth and development of lambs, and the inheritance patterns of FecB. The results showed that there were three genotypes of FecB in the Suhu meat sheep population, namely the AA genotype, AG genotype, and GG genotype. FecB in this population has a moderate polymorphism (0.25 < PIC < 0.5), and deviates from Hardy–Weinberg disequilibrium (p < 0.05). The litter size of GG genotype ewes was significantly higher than that with the AG and AA genotypes (p < 0.01). A Chi-square test showed that the inheritance patterns of FecB follows Mendel's Laws of Inheritance (p > 0.05). An association analysis of different genotypes of FecB with body weight and body size of Suhu meat sheep at birth and weaning revealed that FecB adversely affects the early growth and development of Suhu meat sheep. In summary, FecB can improve the litter size of ewes but it has negative effects on the early growth and survival rate of lambs in sheep. Therefore, FecB test results and feeding management measures should be comprehensively applied to improve the reproductive performance of ewes, the survival rate and production performance of lambs in sheep production, and thus improve the economic benefits of sheep farms. [ABSTRACT FROM AUTHOR]

Mendelian genetics are essential for students seeking to comprehend the complexities of inheritance; although fundamental, these biology concepts are difficult for students to understand. This study examined the effectiveness of task-based learning (TBL) in enhancing the students' conceptual understanding of the Patterns of Mendelian Genetics. A pretest and posttest quasi-experimental research design involved an experimental and a control group. An Intrinsic Motivation Inventory questionnaire was utilized to assess the level of intrinsic motivation for task evaluation for the experimental group. Paired t-test was used to compare the pretest and post-test results. Before the intervention, both groups had a low conceptual understanding of the topic. At the end of the intervention, both groups had significantly increased their performances from pretest to posttest scores. The study revealed that TBL is more effective than Traditional Lecture-Based Instruction (TLI), as seen in their enhanced student performance, implying the effectiveness of the TBL as an innovative instructional approach. Participants from the experimental group expressed enjoyment, competence, and ownership of their task activities, and they did not feel nervous and anxious about doing the tasks. Pearson rcorrelation was used to establish a relationship among the variables. Perceived choice, pressure/tension, and student performance in the experimental group have low positive correlations, and perceived choice, interest/enjoyment, and performance have a negligible correlation. This approach is highly commendable for biology instruction. By illuminating the effectiveness of active learning in improving student's conceptual understanding, this study bridges the gap between theoretical-practical gap in genetics via active learning effectiveness. [ABSTRACT FROM AUTHOR]

Copyright of Revista Iberoamericana de Ciencia, Tecnologia y Sociedad is the property of Centro de Estudios sobre Ciencia, Desarrollo y Educacion Superior and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The article discusses the intersection of genetic testing and actuarial science in the context of life insurance. It highlights the complexities of genetic information, emphasizing that genetic variation is not limited to single-gene disorders like Huntington's disease. The article explores the potential for adverse selection in insurance and the need for actuaries to rely on medical studies to make underwriting decisions. It also examines the regulatory responses to genetic information in different countries. The author concludes that while genetic testing has not yet fully integrated into mainstream medicine, there is still a role for actuaries in understanding and navigating the implications of genetic information in insurance. [Extracted from the article]

The article offers information on the relationship between genetics education and the development of genetic essentialism regarding race. Topics include the historical justifications for racial prejudice based on hereditary grounds; the concept of genetic essentialism; and the impact of basic genetics education on the formation of essentialist beliefs about race.

Background: In this study, we used network pharmacology and molecular docking combined with vitro experiments to explore the potential mechanism of action of Gualou Qumai pill (GLQMP) against DKD. Methods: We screened effective compounds and drug targets using Chinese medicine systemic pharmacology database and analysis platform and Chinese medicine molecular mechanism bioinformatics analysis tools; and searched for DKD targets using human online Mendelian genetics and gene cards. The potential targets of GLQMP for DKD were obtained through the intersection of drug targets and disease targets. Cytoscape software was applied to build herbal medicine-active compound-target-disease networks and analyze them; protein-protein interaction networks were analyzed using the STRING database platform; gene ontology and Kyoto Encyclopedia of Genes and Genomes were used for gene ontology and gene and genome encyclopedia to enrich potential targets using the DAVID database; and the AutoDock Vina 1.1.2 software for molecular docking of key targets with corresponding key components. In vitro experiments were validated by CCK8, oil red O staining, TC, TG, RT-qPCR, and Western blot. Results: Through network pharmacology analysis, a total of 99 potential therapeutic targets of GLQMP for DKD and the corresponding 38 active compounds were obtained, and 5 core compounds were identified. By constructing the protein-protein interaction network and performing network topology analysis, we found that PPARA and PPARG were the key targets, and then we molecularly docked these two key targets with the 38 active compounds, especially the 5 core compounds, and found that PPARA and PPARG had good binding ability with a variety of compounds. In vitro experiments showed that GLQMP was able to ameliorate HK-2 cell injury under high glucose stress, improve cell viability, reduce TC and TG levels as well as decrease the accumulation of lipid droplets, and RT-qPCR and Western blot confirmed that GLQMP was able to promote the expression levels of PPARA and PPARG. Conclusion: Overall, this study revealed the active compounds, important targets and possible mechanisms of GLQMP treatment for DKD, and conducted preliminary verification experiments on its correctness, provided novel insights into the treatment of DKD by GLQMP. [ABSTRACT FROM AUTHOR]

Copyright of Formación Universitaria is the property of Centro de Informacion Tecnologica (CIT) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Episodic ataxias are rare neurological disorders characterized by recurring episodes of imbalance and coordination difficulties. Obtaining definitive molecular diagnoses poses challenges, as clinical presentation is highly heterogeneous, and literature on the underlying genetics is limited. While the advent of high-throughput sequencing technologies has significantly contributed to Mendelian disorders genetics, interpretation of variants of uncertain significance and other limitations inherent to individual methods still leaves many patients undiagnosed. This study aimed to investigate the utility of multiomics for the identification and validation of molecular candidates in a cohort of complex cases of ataxia with episodic presentation. Methods: Eight patients lacking molecular diagnosis despite extensive clinical examination were recruited following standard genetic testing. Whole genome and RNA sequencing were performed on samples isolated from peripheral blood mononuclear cells. Integration of expression and splicing data facilitated genomic variants prioritization. Subsequently, long-read sequencing played a crucial role in the validation of those candidate variants. Results: Whole genome sequencing uncovered pathogenic variants in four genes (SPG7, ATXN2, ELOVL4, PMPCB). A missense and a nonsense variant, both previously reported as likely pathogenic, configured in trans in individual #1 (SPG7: c.2228T>C/p.I743T, c.1861C>T/p.Q621*). An ATXN2 microsatellite expansion (CAG32) in another late-onset case. In two separate individuals, intronic variants near splice sites (ELOVL4: c.541 + 5G>A; PMPCB: c.1154 + 5G>C) were predicted to induce loss-of-function splicing, but had never been reported as disease-causing. Long-read sequencing confirmed the compound heterozygous variants configuration, repeat expansion length, as well as splicing landscape for those pathogenic variants. A potential genetic modifier of the ATXN2 expansion was discovered in ZFYVE26 (c.3022C>T/p.R1008*). Conclusion: Despite failure to identify pathogenic variants through clinical genetic testing, the multi-omics approach enabled the molecular diagnosis in 50% of patients, also giving valuable insights for variant prioritization in remaining cases. The findings demonstrate the value of long-read sequencing for the validation of candidate variants in various scenarios. Our study demonstrates the effectiveness of leveraging complementary omics technologies to unravel the underlying genetics in patients with unresolved rare diseases such as ataxia. Molecular diagnoses not only hold significant promise in improving patient care management, but also alleviates the burden of diagnostic odysseys, more broadly enhancing quality of life. [ABSTRACT FROM AUTHOR]

This document is a letter published in the journal Neurological Sciences. The authors conducted a study using Mendelian randomization analysis to explore the causal relationship between 25-hydroxyvitamin D (25(OH)D) levels and the risk of developing neuromyelitis optica spectrum disorder (NMOSD). They used genome-wide association study (GWAS) data on NMOSD and 25(OH)D levels to analyze the genetic variations and their effects on the disease. The results showed no strong evidence of a causal association between 25(OH)D levels and NMOSD risk in a population of European ancestry. However, a causal relationship was observed between genetically predicted 25(OH)D levels and AQP4-ab-positive NMOSD risk. The study suggests that low vitamin D levels may be a risk factor for AQP4-ab-positive NMOSD and highlights the importance of further research in this area. [Extracted from the article]

High levels of ADAM17 activity have emerged as an important mediator in severe COVID-19. This study aims to characterize eventual causal relationships between ADAM17 and COVID-19. Using Mendelian randomization analyses, we examined the causal effects of circulating ADAM17 on COVID-19 outcomes using summary statistics from large, genome-wide association studies of ADAM17 (up to 35,559 individuals) from the Icelandic Cancer Project and deCODE genetics, as well as critically ill COVID-19 patients (cases: 13,769; controls: 1,072,442), hospitalized COVID-19 patients (cases: 32,519; controls: 2,062,805) and reported SARS-CoV-2 infections (cases: 122,616; controls: 2,475,240) from the COVID-19 Host Genetics Initiative. The Mendelian randomization (MR) analyses demonstrated that a 1 standard deviation increase in genetically determined circulating ADAM17 (extracellular domain) was associated with an increased risk of developing critical ill COVID-19 (odds ratio [OR] = 1.26, 95% confidence interval [CI]:1.03–1.55). The multivariable MR analysis suggested a direct causal role of circulating ADAM17 (extracellular domain) in the risk of developing critical COVID-19 (OR = 1.09; 95% CI:1.01–1.17) when accounting for body mass index. No causal effect for the cytoplasmic domain of ADAM17 on COVID-19 was observed. Our results suggest that an increased genetic susceptibility to elevated levels of circulating ADAM17 (extracellular domain) is associated with a higher risk of suffering from severe COVID-19, strengthening the idea that the timely selective inhibition of ADAM17 could be a potential therapeutic target worthy of investigation. [ABSTRACT FROM AUTHOR]

Meiotic drive biases the transmission of alleles in heterozygous individuals, such that Mendel's law of equal segregation is violated. Most examples of meiotic drive have been discovered over the past century based on causing sex ratio distortion or the biased transmission of easily scoreable genetic markers that were linked to drive alleles. More recently, several approaches have been developed that attempt to identify distortions of Mendelian segregation genome wide. Here, we test a candidate female meiotic drive locus in Drosophila melanogaster, identified previously as causing a ~54:46 distortion ratio using sequencing of large pools of backcross progeny. We inserted fluorescent visible markers near the candidate locus and scored transmission in thousands of individual progeny. We observed a small but significant deviation from the Mendelian expectation; however, it was in the opposite direction to that predicted based on the original experiments. We discuss several possible causes of the discrepancy between the 2 approaches, noting that subtle viability effects are particularly challenging to disentangle from potential small-effect meiotic drive loci. We conclude that pool sequencing approaches remain a powerful method to identify candidate meiotic drive loci but that genotyping of individual progeny at early developmental stages may be required for robust confirmation. [ABSTRACT FROM AUTHOR]

It is generally assumed that parents make a genetically equal contribution to their offspring, but this assumption might not always hold. This is because the expression of a gene can be blocked by methylation during gametogenesis, and the degree of methylation can depend on the origin of the parental gene (imprinting) or by preferential management associated with genetic merit. The first consequences of this for quantitative genetics is that the mean phenotypes of reciprocal heterozygotes need no longer be the same, as would be expected according to Mendelian heritage. We analysed three mare reproductive traits (reproductive efficiency, age at first foaling and foaling number) and three morphological traits (height at withers, thoracic circumference, and scapula‐ischial length) in the Pura Raza Española (PRE) horse population, which possesses a deep and reliable pedigree, making it a perfect breed for analysing the quantitative effect of parent‐of‐origin. The number of animals analysed ranged from 44,038 to 144,191, all of them with both parents known. The model comparison between a model without parent‐of‐origin effects and three different models with parent‐of‐origin effects revealed that both maternal and paternal gametic effects influence all the analysed traits. The maternal gametic effect had a higher influence on most traits, accounting for between 3% and 11% of the total phenotypic variance, while the paternal gametic effect accounted for a higher proportion of variance in one trait, age at first foaling (4%). As expected, the Pearson's correlations between additive breeding values of models that consider parent‐of‐origin and that do not consider parent‐of‐origin were very high; however, the percentage of coincident animals slightly decreases when comparing animals with the highest estimated breeding values. Ultimately, this work demonstrates that parent‐of‐origin effects exist in horse gene transmission from a quantitative point of view. Additionally, including an estimate of the parent‐of‐origin effect within the PRE horse breeding program could be a great tool for a better parent's selection and that could be of interest for breeders, as this value will determine whether the animals acquire genetic categories and are much more highly valued. [ABSTRACT FROM AUTHOR]

This article presents the results of research on the identification of informative DNA marker systems providing reliable control of the presence of the resistance gene to fusarium wilt Foc1 in white cabbage breeding material. At the beginning of the work, 14 molecular markers taken from the VegMarks database and published sources were tested on isogenic white cabbage lines with contrasting resistance to fusarium wilt (resistant line DT-46 and susceptible line Kb1P). InDel marker M10 and SSR markers Frg13 and Ol10-D01 have been ascertained to show polymorphism between white cabbage forms with contrasting resistance to fusarium wilt. Also, PCR analysis of segregating F2 population plants of hybrid combination DT-46 × Kb1P using these markers and phytopathology testing have been conducted. As a result of statistical analysis of segregation, it has been found that only SSR marker Ol10-D01 is co-segregated with the trait of resistance to fusarium wilt as expected segregation of F2 plants by genotype 1 : 2 : 1 according to Mendel's law; the least recombination frequency between the resistance gene Foc1 and the marker (1.6%) has just been observed only by this locus and it is highly polymorphic (PIC = 0.51). [ABSTRACT FROM AUTHOR]

Background: Observational studies have shown that matrix metalloproteinases (MMPs) are associated with sepsis. However, it is unknown whether this association represents a causal relationship. Methods: Mendelian randomization (MR) analysis was conducted to assess the potential causal role of circulating MMPs in sepsis. Single nucleotide polymorphisms (SNPs) associated with circulating MMPs levels were used as instrumental variables (IVs). In a sepsis genome-wide association study comprising 1573 cases and 454,775 European ancestry controls, we examined these IVs' effects using a two-sample MR study. Causal estimates were calculated using inverse variance weighting (IVW), the weighted median method, and MR-Egger analysis. Results: Genetically predict that MMP-1 (OR = 1.011, 95% CI 0.772–1.325, p = 0.936), MMP-3 (OR = 1.036, 95% CI 0.862–1.244, p = 0.707), MMP-7 (OR = 1.206, 95% CI 0.960–1.515, p = 0.108), MMP-8 (OR = 1.041, 95% CI 0.949–1.144, p = 0.395), MMP-9 (OR = 1.101, 95% CI 0.831–1.458, p = 0.503), MMP-10 (OR = 1.028, 95% CI 0.840–1.260, p = 0.789) was not associated with the risk of sepsis. Conclusions: The MR study does not provide evidence that circulating levels of MMPs (1, 3, 7, 8, 9, 10) were the causes of sepsis. [ABSTRACT FROM AUTHOR]

Most human traits are influenced by dozens, hundreds, or thousands of genes working together, not by single genes. Although some genes' effects are stronger and others are weaker, few genes and gene variants have large effects on phenotype. Rather, the tiny effects of many genes and gene variants, in concert with an individual's environment, are integrated to produce a particular phenotype (Visscher et al. 2017). As genes can vary considerably in the strength of their effects on particular traits, the genes in the model differ by the amount of height added/subtracted. [Extracted from the article]

Our understanding of plant biology has been revolutionized by modern genetics and biochemistry. However, biochemical genetics can be traced back to the foundation of Mendelian genetics; indeed, one of Mendel's milestone discoveries of seven characteristics of pea plants later came to be ascribed to a mutation in a starch branching enzyme. Here, we review both current and historical strategies for the elucidation of plant metabolic pathways and the genes that encode their component enzymes and regulators. We use this historical review to discuss a range of classical genetic phenomena including epistasis, canalization, and heterosis as viewed through the lens of contemporary high-throughput data obtained via the array of approaches currently adopted in multiomics studies. [ABSTRACT FROM AUTHOR]

Since the rediscovery of Mendelian genetics over a century ago, there has been much debate about the evolutionary importance of mutations with large phenotypic effects. While population genetic models predict that large-effect mutations will typically contribute to adaptation following an abrupt change in environment, the prediction applies to populations of stable size and overlooks the effects of population size change on adaptation (e.g., population decline following habitat loss; growth during range expansion). We evaluate the phenotypic and fitness effects of mutations contributing to adaptation immediately following an abrupt environmental shift that alters both selection and population size dynamics. We show that large-effect mutations are likely to contribute to adaptation in populations declining to a new carrying capacity, somewhat smaller-effect mutations contribute to evolutionary rescue, and small-effect mutations predominate in growing populations. We also show that the relative contributions of positively selected and overdominant mutations to adaptation depend on interactions between the phenotypic effect size distribution for new mutations and the specific form of population size change during adaptation (i.e., growth, decline, or evolutionary rescue). Our results illustrate how population size dynamics can shape the genetic basis of adaptation, which should motivate empirical comparisons of populations adapting in different demographic contexts. [ABSTRACT FROM AUTHOR]

Genomics has revolutionized the field of genetics because we can now study nearly all genes in the genome and carry out genetic studies on (almost) any species. According to gene ontology classification, eight genes were involved in the sugar metabolism in soybean and showed similar functions in I Arabidopsis. i Mutants are often used to study gene function. Mendel postulated transmissible factors, genes, to explain the inheritance of traits. In celebration of the bicentennial of the birth of Gregor Johann Mendel, the genius of genetics, this Special Issue presents seven papers. [Extracted from the article]

Copyright of Philosophy & History of Biology / Filosofia e História da Biologia is the property of Associacao Brasileira de Filosofia e Historia da Biologia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

This article emphasizes the importance of recognizing and giving credit to the many contributions that contribute to scientific discoveries. It discusses the challenges of acknowledging the large number of people involved in research and the need to share credit. The article encourages authors to cite others who have conducted similar experiments or research, as well as to acknowledge the collective efforts in creating databases and knowledgebases. It emphasizes the importance of properly citing resources, tools, methods, and web links used in research papers to give credit where it is due and support the continued viability of these resources. [Extracted from the article]

Philippe Huneman's book, "Death: Perspectives from the Philosophy of Biology," explores the development and evolution of the fields of physiology and evolutionary biology in relation to death. Huneman identifies three approaches to addressing death: providentialism, the modern synthesis of Darwinism and Mendelian genetics, and explanatory pluralism. He argues that early evolutionary biologists subscribed to a form of providentialism, which posited that death is justified because it benefits the species or its descendants. However, this view has been debunked over time. Huneman also discusses the work of Marie-François Xavier Bichat and his influence on the field of physiology, as well as the explanations for death provided by evolutionary biologists, such as the antagonistic pleiotropy theory, the mutation accumulation theory, and the disposable soma theory. He concludes by advocating for explanatory pluralism, which acknowledges that not all aspects of death can be explained by a single theory. [Extracted from the article]

Advances in clinical genetic testing, including the introduction of exome sequencing, have uncovered the molecular etiology for many rare and previously unsolved genetic disorders, yet more than half of individuals with a suspected genetic disorder remain unsolved after complete clinical evaluation. A precise genetic diagnosis may guide clinical treatment plans, allow families to make informed care decisions, and permit individuals to participate in N-of-1 trials; thus, there is high interest in developing new tools and techniques to increase the solve rate. Long-read sequencing (LRS) is a promising technology for both increasing the solve rate and decreasing the amount of time required to make a precise genetic diagnosis. Here, we summarize current LRS technologies, give examples of how they have been used to evaluate complex genetic variation and identify missing variants, and discuss future clinical applications of LRS. As costs continue to decrease, LRS will find additional utility in the clinical space fundamentally changing how pathological variants are discovered and eventually acting as a single-data source that can be interrogated multiple times for clinical service. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Forensic Medicine / Fayixue Zazhi is the property of Journal of Forensic Medicine Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The defining feature of both discoveries was the concomitant occurrence of a rare infectious phenotype (i.e., recurrent, multiple bacterial infections), and a distinctive hematoimmunological phenotype (i.e., an endophenotype that was understood to underlie the clinical phenotype), displaying Mendelian inheritance (i.e., complete penetrance). The descriptions of boys with X-linked recessive agammaglobulinemia by Ogden Bruton in 1952 [[1]], and David Gitlin, Charles Janeway and their colleagues in 1953 [[3]-[5]] have long been held to constitute the birth of "primary immunodeficiencies." Coincidentally, Bruton and Kostmann were both pediatricians working for the military, Bruton in the USA and Kostmann in Sweden. It is not coincidental that Kostmann's and Bruton's diseases were designated by their hemato-immunological phenotypes, hereditary neutropenia and agammaglobulinemia, unlike Lutz' epidemodysplasia verrucifomis. [Extracted from the article]

Context: Both Graves disease (GD) and inflammatory bowel disease (IBD) are common autoimmune diseases that severely damage a patient’s quality of life. Previous epidemiological studies have suggested associations between GD and IBD. However, whether a causal relationship exists between these 2 diseases remains unknown. Objective: To infer a causal relationship between GD and IBD using bidirectional 2-sample Mendelian randomization (MR). Methods: We performed bidirectional 2-sample MR to infer a causal relationship between GD and IBD using genome-wide association study summary data obtained from Biobank Japan and the International Inflammatory Bowel Disease Genetic Consortium. Several methods (random-effect inverse variance weighted, weighted median, MR-Egger regression, and MR-PRESSO) were used to ensure the robustness of the causal effect. Heterogeneity was measured based on Cochran’s Q value. Horizontal pleiotropy was evaluated by MR-Egger regression and leave-one-out analysis. Results: Genetically predicted IBD may increase the risk of GD by 24% (odds ratio [OR] 1.24, 95% CI 1.01-1.52, P=.041). Crohn disease (CD) may increase the risk of GD, whereas ulcerative colitis (UC) may prevent patients from developing GD. Conversely, genetically predicted GD may slightly increase the risk of CD, although evidence indicating that the presence of GD increased the risk of UC or IBD was lacking. Outlier -corrected results were consistent with raw causal estimates. Conclusion: Our study revealed a potentially higher comorbidity rate for GD and CD. However, UC might represent a protective factor for GD. The underlying mechanism and potential common pathways await discovery. [ABSTRACT FROM AUTHOR]

A mathematical model that simulates malaria transmission under the influence of transgenic mosquitoes refractory to malaria is presented in this paper. The zygosity of transgenic mosquitoes is taken into account and, consequently, the total population of mosquitoes is comprised of wild type and heterozygous and homozygous transgenic mosquitoes. These three mosquito varieties interact by mating and competition, and the genetic characteristics of their resulting offspring are in accordance with Mendelian genetics or the mutagenic chain reaction (MCR) technique. Although the incorporation of transgenic mosquitoes into the ecosystem reduces the incidence of malaria, the model also takes into account the importance of completing treatment in individuals with confirmed infection and the imminent risk of increased environmental temperature. [ABSTRACT FROM AUTHOR]

Graduates in biology or genetics learn Mendel's laws and Hardy–Weinberg equilibrium as students, and they know, use, and sometimes teach these concepts. However, it is unusual to learn about stochastic processes during the graduate studies of these topics, although the applications of Markov chains in the fields of genetics or biology are increasing. In this paper, and from Mendel's Laws, we are going to obtain an example of the Hardy–Weinberg Equilibrium that can be used to teach it. In the demonstration, stochastic processes theory and Markov chains will be used, in order to develop the transition matrix. In this way, we obtain an example that can be used to illustrate an explanation that involves, through Mendel's laws, Hardy–Weinberg equilibrium for degree students, and stochastic processes for advanced students in biology or genetic sciences (predoctoral students at university). In this example, we are going to use the Scientific Workplace version 6.0 software. [ABSTRACT FROM AUTHOR]

The rapid development of genetics at the beginning of the 20th century coincided with the introduction of the fruit fly Drosophila melanogaster into laboratory research. Thomas Hunt Morgan and his students used this humble organism to confirm Mendelian genetics, establish chromosome theory and craft the first ever genetic maps. During this process they created a standardized, ideal genetic model animal that is continued to be used in research to this day. By removing the background genetic variance of the natural populations, this standardization blindsided some researchers, like Hermann Joseph Muller to the importance of genetic diversity. In contrast, others, like Theodosius Dobzhansky, used the genetic variance of a related species, Drosophila pseudoobscura to demonstrate the importance of diversity in natural populations. Muller and Dob zhansky both generalized their observations to human populations and their debate about the merits and vices of positive eugenics and the possible dangers or advantages of genetic diversity still resonate today, in an era of genome editing, preimplantation diagnostics and embryo selection. [ABSTRACT FROM AUTHOR]

The harmful effects of close inbreeding have been recognized for centuries and, with the rise of Mendelian genetics, was realized to be an effect of homozygosis. This historical background led to great interest in ways to quantify inbreeding, its depression effects on the phenotype and flow‐on effects on mate choice and other aspects of behavioral ecology. The mechanisms and cues used to avoid inbreeding are varied and include major histocompatibility complex (MHC) molecules and the peptides they transport as predictors of the degree of genetic relatedness. Here, we revisit and complement data from a Swedish population of sand lizards (Lacerta agilis) showing signs of inbreeding depression to assess the effects of genetic relatedness on pair formation in the wild. Parental pairs were less similar at the MHC than expected under random mating but mated at random with respect to microsatellite relatedness. MHC clustered in groups of RFLP bands but no partner preference was observed with respect to partner MHC cluster genotype. Male MHC band patterns were unrelated to their fertilization success in clutches selected for analysis on the basis of showing mixed paternity. Thus, our data suggest that MHC plays a role in pre‐copulatory, but not post‐copulatory partner association, suggesting that MHC is not the driver of fertilization bias and gamete recognition in sand lizards. [ABSTRACT FROM AUTHOR]