Frequency In Population Research Articles

Molecular characterization of Bertiella studeri infecting a primate in South India.

Bertiella spp. is a mite-borne cestode parasite that inhabits the small intestine of wide range of mammals, including non-human primates. In the present study, the morphological and molecular analysis of Bertiella studeri recovered from the small intestine of a bonnet macaque (Macaca radiata) from Wayanad, Kerala (South India) was performed. Acetic alum carmine staining identified the cestode morphologically based on the characters like broader proglottids, which contain irregularly alternating genital pores, single set of reproductive organs, 280 testes and a tubular transverse uterus. Molecular characterization was done using 18SrRNA, ITS1-5.8S and COX1 genes. Phylogenetic trees were constructed using MEGA X based on the Maximum Likelihood (ML) method (Hasegawa-Kishino-Yano (HKY) model). Cytochrome oxidase I gene could detect the existence of genetic variation in the parasite from two different hosts viz., monkey (Kerala, Argentina, and Kenya) and human (Sri Lanka). A minimum spanning network of haplotypes was generated by the haplotype networking with the above sequences using the popARTv1.7. Haplotype analysis based on COX1 revealed that the parasite haplotype was different in each country with highest population frequency in Sri Lanka.

Rapid evolution of consumptive and non-consumptive predator effects on prey population densities, bioenergetics and stoichiometry.

Predators can strongly influence prey populations not only through consumptive effects (CE) but also through non-consumptive effects (NCE) imposed by predation risk. Yet, the impact of NCE on bioenergetic and stoichiometric body contents of prey, traits that are shaping life histories, population and food web dynamics, is largely unknown. Moreover, the degree to which NCE can evolve and can drive evolution in prey populations is rarely studied. A 6-week outdoor mesocosm experiment with Caged-Fish (NCE) and Free-Ranging-Fish (CE and NCE) treatments was conducted to quantify and compare the effects of CE and NCE on population densities, bioenergetic and stoichiometric body contents of Daphnia magna, a keystone species in freshwater ecosystems. We tested for evolution of CE and NCE by using experimental populations consisting of D. magna clones from two periods of a resurrected natural pond population: a pre-fish period without fish and a high-fish period with high predation pressure. Both Caged-Fish and Free-Ranging-Fish treatments decreased the body size and population densities, especially in Daphnia from the high-fish period. Only the Free-Ranging-Fish treatment affected bioenergetic variables, while both the Caged-Fish and Free-Ranging-Fish treatments shaped body stoichiometry. The effects of CE and NCE were different between both periods indicating their rapid evolution in the natural resurrected population. Both the Caged-Fish and Free-Ranging-Fish treatments changed the clonal frequencies of the experimental Daphnia populations of the pre-fish as well as the high-fish period, indicating that not only CE but also NCE induced clonal sorting, hence rapid evolution during the mesocosm experiment in both periods. Our results demonstrate that CE as well as NCE have the potential to change not only the body size and population density but also the bioenergetic and stoichiometric characteristics of prey populations. Moreover, we show that these responses not only evolved in the studied resurrected population, but that CE and NCE also caused differential rapid evolution in a time frame of 6 weeks (ca. four to six generations). As NCE can evolve as well as can drive evolution, they may play an important role in shaping eco-evolutionary dynamics in predator-prey interactions.

Diagnostic yield of exome and genome sequencing after non-diagnostic multi-gene panels in patients with single-system diseases

BackgroundThough next-generation sequencing (NGS) tests like exome sequencing (ES), genome sequencing (GS), and panels derived from exome and genome data (EGBP) are effective for rare diseases, the ideal diagnostic approach is debated. Limited research has explored reanalyzing raw ES and GS data post-negative EGBP results for diagnostics. Results: We analyzed complete ES/GS raw sequencing data from Mayo Clinic's Program for Rare and Undiagnosed Diseases (PRaUD) patients to assess whether supplementary findings could augment diagnostic yield. ES data from 80 patients (59 adults) and GS data from 20 patients (10 adults), averaging 43 years in age, were analyzed. Most patients had renal (n=44) and auto-inflammatory (n=29) phenotypes. Ninety-six cases had negative findings and in four cases additional genetic variants were found, including a variant related to a recently described disease (RRAGD-related hypomagnesemia), a variant missed due to discordant inheritance pattern (COL4A3), a variant with high allelic frequency (NPHS2) in the general population, and a variant associated with an initially untargeted phenotype (HNF1A). Conclusion: ES and GS show diagnostic yields comparable to EGBP for single-system diseases. However, EGBP's limitations in detecting new disease-associated genes underscore the necessity for periodic updates.

Individual and population-level variability in HLA-DR associated immunogenicity risk of biologics used for the treatment of rheumatoid arthritis.

While conventional in silico immunogenicity risk assessments focus on measuring immunogenicity based on the potential of therapeutic proteins to be processed and presented by a global population-wide set of human leukocyte antigen (HLA) alleles to T cells, future refinements might adjust for HLA allele frequencies in different geographic regions or populations, as well for as individuals in those populations. Adjustment by HLA allele distribution may reveal risk patterns that are specific to population groups or individuals, which current methods that rely on global-population HLA prevalence may obscure. This analysis uses HLA frequency-weighted binding predictions to define immunogenicity risk for global and sub-global populations. A comparison of assessments tuned for North American/European versus Japanese/Asian populations suggests that the potential for anti-therapeutic responses (anti-therapeutic antibodies or ATA) for several commonly prescribed Rheumatoid Arthritis (RA) therapeutic biologics may differ, significantly, between the Caucasian and Japanese populations. This appears to align with reports of differing product-related immunogenicity that is observed in different populations. Further definition of population-level (regional) and individual patient-specific immunogenic risk profiles may enable prescription of the RA therapeutic with the highest probability of success to each patient, depending on their population of origin and/or their individual HLA background. Furthermore, HLA-specific immunogenicity outcomes data are limited, thus there is a need to expand HLA-association studies that examine the relationship between HLA haplotype and ATA in the clinic.

In silico evidence that substitution of glycine for valine (p.G8V) in a common variant of TMPRSS2 isoform 1 increases accessibility to an endocytic signal: Implication for SARS-cov-2 entry into host cells and susceptibility to COVID-19

The TMPRSS2 protease plays a key role in the entry of the SARS-CoV-2 into cells. The TMPRSS2 gene is highly polymorphic in humans, and some polymorphisms may affect the susceptibility to COVID-19 or disease severity. rs75603675 (c.23G > T) is a missense variant that causes the replacement of glycine with valine at position 8 (p.G8V) in the TMPRSS2 isoform 1. According to GnomAD v4.0.0 database, the allele frequency of the rs75603675 on a global scale is 38.10 %, and range from 0.92 % in East Asian to 40.77 % in non-Finnish European (NFE) population. We analyzed the occurrence of the rs75603675 in two cohorts of patients, the first with severe/critical COVID-19 enrolled in a French hospital (42 patients), and the second with predominantly asymptomatic/pauci-symptomatic/mild COVID-19 enrolled in an Italian hospital (69 patients). We found that the TMPRSS2-c.23T minor allele frequency was similar in the two cohorts, 46.43 % and 46.38 %, respectively, and higher than the frequency in the NFE population (40.77 %). Chi-square test provided significant results (p < 0.05) when the genotype data (TMPRSS2-c.23T/c.23T homozygotes + TMPRSS2-c.23G/c.23T heterozygotes vs. TMPRSS2-c.23G/c.23G homozygotes) of the two patient groups were pooled and compared to the expected data for the NFE population, suggesting a possible pathogenetic mechanism of the p.G8V substitution. We explored the possible effects of the p.G8V substitution and found that the N-terminal region of the TMPRSS2 isoform 1 contains a signal for clathrin/AP-2-dependent endocytosis. In silico analysis predicted that the p.G8V substitution may increase the accessibility to the endocytic signal, which could help SARS-CoV-2 enter cells.

Efficient enzyme-free method to assess the development and maturation of the innate and adaptive immune systems in the mouse colon

Researchers who aim to globally analyze the gastrointestinal immune system via flow cytometry have many protocol options to choose from, with specifics generally tied to gut wall layers of interest. To get a clearer idea of the approach we should use on full-thickness colon samples from mice, we first undertook a systematic comparison of three tissue dissociation techniques: two based on enzymatic cocktails and the other one based on manual crushing. Using flow cytometry panels of general markers of lymphoid and myeloid cells, we found that the presence of cell-surface markers and relative cell population frequencies were more stable with the mechanical method. Both enzymatic approaches were associated with a marked decrease of several cell-surface markers. Using mechanical dissociation, we then developed two minimally overlapping panels, consisting of a total of 26 antibodies, for serial profiling of lymphoid and myeloid lineages from the mouse colon in greater detail. Here, we highlight how we accurately delineate these populations by manual gating, as well as the reproducibility of our panels on mouse spleen and whole blood. As a proof-of-principle of the usefulness of our general approach, we also report segment- and life stage-specific patterns of immune cell profiles in the colon. Overall, our data indicate that mechanical dissociation is more suitable and efficient than enzymatic methods for recovering immune cells from all colon layers at once. Additionally, our panels will provide researchers with a relatively simple tool for detailed immune cell profiling in the murine gastrointestinal tract, regardless of life stage or experimental conditions.

Coinfection frequency in water flea populations is a mere reflection of parasite diversity

In nature, parasite species often coinfect the same host. Yet, it is not clear what drives the natural dynamics of coinfection prevalence. The prevalence of coinfections might be affected by interactions among coinfecting species, or simply derive from parasite diversity. Identifying the relative impact of these parameters is crucial for understanding patterns of coinfections. We studied the occurrence and likelihood of coinfections in natural populations of water fleas (Daphnia magna). Coinfection prevalence was within the bounds expected by chance and parasite diversity had a strong positive effect on the likelihood of coinfections. Additionally, coinfection prevalence increased over the season and became as common as a single infection. Our results demonstrate how patterns of coinfection, and particularly their temporal variation, are affected by overlapping epidemics of different parasites. We suggest that monitoring parasite diversity can help predict where and when coinfection prevalence will be high, potentially leading to increased health risks to their hosts.

PNPLA3 fatty liver allele was fixed in Neanderthals and segregates neutrally in humans

ObjectiveFat deposition is modulated by environmental factors and genetic predisposition. Genome-wide association studies identified PNPLA3 p.I148M (rs738409) as a common variant that increases risk of developing liver steatosis. When and...

Multiomic analysis of uterine leiomyomas in self-described Black and White women: molecular insights into health disparities

Black women are at an increased risk of developing uterine leiomyomas and experiencing worse disease prognosis than White women. Epidemiologic and molecular factors have been identified as underlying these disparities, but there remains a paucity of deep, multiomic analysis investigating molecular differences in uterine leiomyomas from Black and White patients. To identify molecular alterations within uterine leiomyoma tissues correlating with patient race by multiomic analyses of uterine leiomyomas collected from cohorts of Black and White women. We performed multiomic analysis of uterine leiomyomas from Black (42) and White (47) women undergoing hysterectomy for symptomatic uterine leiomyomata. In addition, our analysis included the application of orthogonal methods to evaluate fibroid biomechanical properties, such as second harmonic generation microscopy, uniaxial compression testing, and shear-wave ultrasonography analyses. We found a greater proportion of MED12 mutant uterine leiomyomas from Black women (>35% increase; Mann-Whitney U, P<.001). MED12 mutant tumors exhibited an elevated abundance of extracellular matrix proteins, including several collagen isoforms, involved in the regulation of the core matrisome. Histologic analysis of tissue fibrosis using trichrome staining and secondary harmonic generation microscopy confirmed that MED12 mutant tumors are more fibrotic than MED12 wild-type tumors. Using shear-wave ultrasonography in a prospectively collected cohort, Black patients had fibroids that were firmer than White patients, even when similar in size. In addition, these analyses uncovered ancestry-linked expression quantitative trait loci with altered allele frequencies in African and European populations correlating with differential abundance of several proteins in uterine leiomyomas independently of MED12 mutation status, including tetratricopeptide repeat protein 38. Our study shows that Black women have a higher prevalence of uterine leiomyomas harboring mutations in MED12 and that this mutational status correlates with increased tissue fibrosis compared with wild-type uterine leiomyomas. Our study provides insights into molecular alterations correlating with racial disparities in uterine leiomyomas and improves our understanding of the molecular etiology underlying uterine leiomyoma development within these populations.

Locally adaptive inversions in structured populations.

Inversions have been proposed to facilitate local adaptation, by linking together locally coadapted alleles at different loci. Prior work addressing this question theoretically has considered the spread of inversions in "continent-island" scenarios in which there is a unidirectional flow of maladapted migrants into the island population. In this setting, inversions capturing locally adaptive haplotypes are most likely to invade when selection is weak, because stronger local selection (i) more effectively purges maladaptive alleles and (ii) generates linkage disequilibrium between adaptive alleles, thus lessening the advantage of inversions. We show this finding only holds under limited conditions by studying the establishment of inversions in a more general two-deme model, which explicitly considers the dynamics of allele frequencies in both populations linked by bidirectional migration. In this model, the level of symmetry between demes can be varied from complete asymmetry (continent-island) to complete symmetry. For symmetric selection and migration, strong selection increases the allele frequency divergence between demes thereby increasing the frequency of maladaptive alleles in migrants, favoring inversions-the opposite of the pattern seen in the asymmetric continent-island scenario. We also account for the likelihood that a new inversion captures an adaptive haplotype in the first instance. When considering the combined process of capture and invasion in "continent island" and symmetric scenarios, relatively strong selection increases inversion establishment probability. Migration must also be low enough that the inversion is likely to capture an adaptive allele combination, but not so low as to eliminate the inversion's advantage. Overall, our analysis suggests that inversions are likely to harbor larger effect alleles that experience relatively strong selection.

Abstract PO2-20-05: Onco-Genome Brazil: Mapping Breast and Prostate Cancer in the Brazilian Public Health System

Abstract Background: Breast and prostate cancers are the most common malignancies diagnosed in women and men respectively, and present with great clinical heterogeneity, even in tumors with the same phenotypic characteristics. Somatic and germline molecular alterations in DNA may have prognostic and predictive impact, influencing response to therapies and overall survival. In addition, the evaluation of germline mutations can help identify individuals and families at higher risk for developing cancer. Aims: Our aim is to characterize the somatic and germline genomic landscape of women with locally advanced HER2-positive breast cancer and men with metastatic prostate cancer from Brazil. Secondarily, we aim to identify genetic variants associated with tumor prognosis and treatment response, identify patients carrying pathogenic alterations in cancer-predisposing genes, and characterize the genetic ancestry of the population included in the study. Trial design: This observational multicenter cohort study (NCT05306600) will include 550 adult patients from the five macro-regions of Brazil, divided into two arms: 1) breast cancer and 2) prostate cancer. Clinical and pathological data will be collected, as well as DNA samples from peripheral blood and tumor tissue. Whole-exome sequencing (WES) will be performed to identify variants that may be drivers and/or actionable in a specific patient or tumor. These variants will be interpreted and classified according to their population frequencies, in silico predictors, functional studies, and literature data, following international guidelines proposed by expert societies. This trial is supported by the Ministry of Health in Brazil and includes patients of the Public Health System. Eligibility criteria: In arm 1, the inclusion criteria are patients with a histological diagnosis of breast carcinoma with overexpression of HER-2, clinical stage II or III, and undergoing neoadjuvant treatment with chemotherapy plus trastuzumab. In arm 2, the criteria are patient with histological diagnosis of prostate adenocarcinoma, currently in clinical stage IV. Patients without availability of biological material collection are excluded from the study, as well as patients in whom there was no central confirmation of required histology. Statistical methods: Univariate and multivariate analyses will be conducted to evaluate the possible effect of specific genes or mutations on the investigated outcomes, including tumor prognosis and treatment response. Discussion: Currently, 265 participants have already been included in the study, 150 in arm 1 and 115 in arm 2. This trial will contribute to the construction of a robust database that should provide a better understanding of the genomic profile of patients with breast and prostate cancer in Brazil. For more information about the trial, please contact Daniela Rosa (daniela.rosa@hmv.org.br). Citation Format: Jaqueline Schuch, Cláudia Bordignon, Mahira Rosa, Angélica de Baumont, Marina Bessel, Gabriel Macedo, Daniela Rosa. Onco-Genome Brazil: Mapping Breast and Prostate Cancer in the Brazilian Public Health System [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-20-05.

Cardiac arrhythmia and epilepsy genetic variants in sudden unexpected death in epilepsy.

Sudden Unexpected Death in Epilepsy (SUDEP) is the leading epilepsy-related cause of death, affecting approximately 1 per 1,000 individuals with epilepsy per year. Genetic variants that affect autonomic function, such as genes associated with cardiac arrhythmias, may predispose people with epilepsy to greater risk of both sudden cardiac death and SUDEP. Advances in next generation sequencing allow for the exploration of gene variants as potential biomarkers. Genetic testing for the presence of cardiac arrhythmia and epilepsy gene variants was performed via genetic panels in 39 cases of SUDEP identified via autopsy by the Ontario Forensic Pathology Service. Variants were summarized by in-silico evidence for pathogenicity from 4 algorithms (SIFT, PolyPhen-2, PROVEAN, Mutation Taster) and allele frequencies in the general population (GnomAD). A maximum credible population allele frequency of 0.00004 was calculated based on epilepsy prevalence and SUDEP incidence to assess whether a variant was compatible with a pathogenic interpretation. Median age at the time of death was 33.3 years (range: 2, 60). Fifty-nine percent (n=23) were male. Gene panels detected 62 unique variants in 45 genes: 19 on the arrhythmia panel and 26 on the epilepsy panel. At least one variant was identified in 28 (72%) of decedents. Missense mutations comprised 57 (92%) of the observed variants. At least three in silico models predicted 12 (46%) cardiac arrhythmia panel missense variants and 20 (65%) epilepsy panel missense variants were pathogenic. Population allele frequencies were <0.00004 for 11 (42%) of the cardiac variants and 10 (32%) of the epilepsy variants. Together, these metrics identified 13 SUDEP variants of interest. Nearly three-quarters of decedents in this SUDEP cohort carried variants in comprehensive epilepsy or cardiac arrhythmia gene panels, with more than a third having variants in both panels. The proportion of decedents with cardiac variants aligns with recent studies of the disproportionate cardiac burden the epilepsy community faces compared to the general population and suggests a possible cardiac contribution to epilepsy mortality. These results identified 13 priority targets for future functional studies of these genes potential role in sudden death and demonstrates the necessity for further exploration of potential genetic contributions to SUDEP.

A modified schedule of multiple aeroallergen ultra-rush immunotherapy in perennial allergic rhinitis: safety, efficacy, and T lymphocyte cell population studies.

This study assessed whether a modified immunotherapy schedule for allergic rhinitis could be safe and efficient. Ultra-rush immunotherapy (URIT) rapidly desensitizes patients to aeroallergens. We aimed to develop a modified URIT protocol in 3 days to achieve the target dose while observing whether it could improve this situation and decrease the time to achieve the maintenance dose. The URIT was exercised in 21 patients with perennial allergic rhinitis. Premeditations were given to the patients 3 days prior to the immunotherapy and during the 3 days injections immunotherapy: pred nisolone, ranitidine, and Airokast/montelukast. Finally, the T cell population frequencies of patients prior to and after immunotherapy, including T helper 1, T helper 2, cytotoxic T lymphocytes, and regulatory T cells, were studied using flow cytometry. During the URIT protocol, 21 patients received 291 injections. Six patients (28.6%) showed systemic reactions in our study. All systemic reactions occurred on the third day by the 1:1 dilution of the maintenance dose. These systemic reactions occurred in three patients after 13 injections, and the three remaining patients showed systemic reactions following the last injection. No systemic reaction was observed on the first and second day of the therapy, and the risk of systemic reaction with every injection was about 2%. Among the T cell populations, CD3+ and CD8+ cells decreased significantly. The findings emphasized that URIT, alongside premedication with a high dose of antihistamine, helped to achieve the maintenance dose and control clinical manifestations.

Effect of propofol and isoflurane on NK Cells: A pilot study on perioperative breast cancer patients from Eastern India

Introduction: In onco-anesthesiology, the selection between intravenous and volatile anesthetics for maintaining NK cell response during cancer surgery has been an ambiguous area. In the absence of any such comparative Indian report, this pilot study aimed to investigate the effect of intravenous anesthetic, Propofol, and volatile anesthetic, Isoflurane on the NK cell-mediated immune-inflammatory response of perioperative breast cancer patients. Materials and Methods: Treatment naive breast cancer patients (N, 50) selected for surgery were randomly subjected to either Isoflurane (N, 25) or Propofol (N, 25) anesthetic group. The peripheral blood samples were collected 1 day before surgery (Pre), 1 h after incision (Intra) and 48 h after surgery (Post). The blood samples were subjected to immunophenotyping, activation, degranulation, and cytokine analysis. Results: The frequency of NK cell populations did not differ between the Isoflurane and Propofol groups irrespective of cancer stage II/III. NK cell degranulation marker CD107a and activation marker CD335 expression were significantly reduced in the postoperative period compared to the preoperative group in the Isoflurane group but Propofol did not inflict such alterations. Both Isoflurane/Propofol elicited similar trends in the cytokine profiles of interleukin (IL)-6, IL-15, interferon (IFN)-g and transforming growth factor (TGF)-β levels. Isoflurane significantly increased IL-8 during the intraoperative period and matrix metalloproteinase (MMP)-9 during the postoperative period whereas no such changes were observed with Propofol. Conclusion: This pilot study indicated that Propofol partially proved better over Isoflurane in maintaining the activation (CD335) and degranulation of NK cells (CD107a) and alleviating inflammation (IL-8 and MMP-9) during the perioperative period in the breast cancer patients.

Comparative single-cell multiplex immunophenotyping of therapy-naive patients with rheumatoid arthritis, systemic sclerosis, and systemic lupus erythematosus shed light on disease-specific composition of the peripheral immune system.

Systemic autoimmune diseases (SADs) are a significant burden on the healthcare system. Understanding the complexity of the peripheral immunophenotype in SADs may facilitate the differential diagnosis and identification of potential therapeutic targets. Single-cell mass cytometric immunophenotyping was performed on peripheral blood mononuclear cells (PBMCs) from healthy controls (HCs) and therapy-naive patients with rheumatoid arthritis (RA), progressive systemic sclerosis (SSc), and systemic lupus erythematosus (SLE). Immunophenotyping was performed on 15,387,165 CD45+ live single cells from 52 participants (13cases/group), using an antibody panel to detect 34 markers. Using the t-SNE (t-distributed stochastic neighbor embedding) algorithm, the following 17 main immune cell types were determined: CD4+/CD57- T cells, CD4+/CD57+ T cells, CD8+/CD161- T cells, CD8+/CD161+/CD28+ T cells, CD8dim T cells, CD3+/CD4-/CD8- T cells, TCRγ/δ T cells, CD4+ NKT cells, CD8+ NKT cells, classic NK cells, CD56dim/CD98dim cells, B cells, plasmablasts, monocytes, CD11cdim/CD172dim cells, myeloid dendritic cells (mDCs), and plasmacytoid dendritic cells (pDCs). Seven of the 17 main cell types exhibited statistically significant frequencies in the investigated groups. The expression levels of the 34 markers in the main populations were compared between HCs and SADs. In summary, 59 scatter plots showed significant differences in the expression intensities between at least two groups. Next, each immune cell population was divided into subpopulations (metaclusters) using the FlowSOM (self-organizing map) algorithm. Finally, 121 metaclusters (MCs) of the 10 main immune cell populations were found to have significant differences to classify diseases. The single-cell T-cell heterogeneity represented 64MCs based on the expression of 34 markers, and the frequency of 23 MCs differed significantly between at least twoconditions. The CD3- non-T-cell compartment contained 57 MCs with 17 MCs differentiating at least two investigated groups. In summary, we are the first to demonstrate the complexity of the immunophenotype of34markers over 15 million single cells in HCs vs. therapy-naive patients withRA, SSc, and SLE. Disease specific population frequencies or expression patterns of peripheral immune cells provide a single-cell data resource to the scientific community.

Genetic Landscape and Clinical Features of Hyperphenylalaninemia in North Ossetia-Alania: High Frequency of P281L and P211T Genetic Variants in the PAH Gene.

This study, conducted in the Republic of North Ossetia-Alania (RNOA), aimed to explore the genetic landscape of hyperphenylalaninemia (HPA) and phenylketonuria (PKU) in the Ossetian population using data from newborn screening (NBS). Through comprehensive molecular genetic analysis of 29 patients with HPA from diverse ethnic backgrounds, two major genetic variants in the PAH gene, P281L and P211T, were identified, constituting 50% of all detected pathogenic alleles in Ossetian patients. Remarkably, these variants exhibited an exceptionally high frequency in the Ossetian population, surpassing global prevalence rates. This study unveiled a notable prevalence of mild forms of HPA (78%), underscoring the importance of genetic counseling for carriers of pathogenic variants in the PAH gene. Moreover, the findings emphasized the necessity for ongoing monitoring of patients with mild forms, as they may lack significant symptoms for diagnosis, potentially impacting offspring. Overall, this research offers valuable insights into the genetic landscape of HPA and PKU in the Ossetian population.

Single nucleotide polymorphism-based biomarker in primary hypertension

Primary hypertension is a multiplex and multifactorial disease influenced by various strong components including genetics. Extensive research such as Genome-wide association studies and candidate gene studies have revealed various single nucleotide polymorphisms (SNPs) related to hypertension, providing insights into the genetic basis of the condition. This review summarizes the current status of SNP research in primary hypertension, including examples of hypertension-related SNPs, their location, function, and frequency in different populations. The potential clinical implications of SNP research for primary hypertension management are also discussed, including disease risk prediction, personalized medicine, mechanistic understanding, and lifestyle modifications.Furthermore, this review highlights emerging technologies and methodologies that have the potential to revolutionize the vast understanding of the basis of genetics in primary hypertension. Gene editing holds the potential to target and correct any kind of genetic mutations that contribute to the development of hypertension or modify genes involved in blood pressure regulation to prevent or treat the condition. Advances in computational biology and machine learning enable researchers to analyze large datasets and identify complex genetic interactions contributing to hypertension risk.In conclusion, SNP research in primary hypertension is rapidly evolving with emerging technologies and methodologies that have the potential to transform the knowledge about genetic basis related to the condition. These advances hold promise for personalized prevention and treatment strategies tailored to an individual's genetic profile ultimately improving patient outcomes and reducing healthcare costs.

Understanding genetic variability: exploring large-scale copy number variants through non-invasive prenatal testing in European populations.

Large-scale copy number variants (CNVs) are structural alterations in the genome that involve the duplication or deletion of DNA segments, contributing to genetic diversity and playing a crucial role in the evolution and development of various diseases and disorders, as they can lead to the dosage imbalance of one or more genes. Massively parallel sequencing (MPS) has revolutionized the field of genetic analysis and contributed significantly to routine clinical diagnosis and screening. It offers a precise method for detecting CNVs with exceptional accuracy. In this context, a non-invasive prenatal test (NIPT) based on the sequencing of cell-free DNA (cfDNA) from pregnant women's plasma using a low-coverage whole genome MPS (WGS) approach represents a valuable source for population studies. Here, we analyzed genomic data of 12,732 pregnant women from the Slovak (9,230), Czech (1,583), and Hungarian (1,919) populations. We identified 5,062 CNVs ranging from 200 kbp and described their basic characteristics and differences between the subject populations. Our results suggest that re-analysis of sequencing data from routine WGS assays has the potential to obtain large-scale CNV population frequencies, which are not well known and may provide valuable information to support the classification and interpretation of this type of genetic variation. Furthermore, this could contribute to expanding knowledge about the central European genome without investing in additional laboratory work, as NIPTs are a relatively widely used screening method.

Genetic, lifestyle and metabolic factors contributing to cardiovascular disease in the Italian population: a literature review.

Cardiovascular diseases (CVD) represent a major health problem worldwide. In Italy, despite the decline in CVD mortality and disability-adjusted life years recently observed, CVD remains the leading cause of death. The development of CVD has a complex and multifactorial etiology that involves environmental, lifestyle/behavioral (e.g., unhealthy diet, physical inactivity, smoking, and alcohol abuse), metabolic, and genetic factors. Although a large number of CVD susceptibility genetic variants have been identified, some seem to confer risk according to the genetic background or ethnicity of the population. Some CVD-associated polymorphisms with appreciable frequency in the Italian population may be important contributors to the development and progression of the most prevalent CVD in the population. This literature review aims to provide an overview of the epidemiology of CVD in Italy, as well as to highlight the main genetic, lifestyle/behavioral, and metabolic factors contributing to CVD risk in this population.

Laboratory and genetic predictors for severe COVID-19 infection

This study aims to identify laboratory and genetic markers important for COVID-19 severity to improve patient assessment and treatment. COVID-19 patients were divided into two groups based on disease severity. Clinical, laboratory (complete blood count, complete biochemical parameters - lactate dehydrogenase (LDH), serum ferritin), and genetic markers (OAS1 rs4767027) were analyzed. A total of 61 COVID-19 patients and 48 negative controls were investigated. Group I showed more often lymphopenia – 3.16 (1.39–3.89) vs 5.61(4.21–7.98), p-0.027 and thrombocytopenia – 165 (75–256) vs 212 (198–349), p-0.031, higher LDH (621 ± 218 U/L vs 312 ± 110 U/L), p-0.014. OAS1 rs4767027 genotype and allele frequencies did not differ significantly from worldwide population frequencies. Lymphopenia and thrombocytopenia are likely associated with immune inflammation and COVID-19 severity. While increased OAS1 transcript levels are correlated with reduced risk of infection, they can contribute to NLRP3 inflammasome activation once the infection has been established.