Genetic Insights Research Articles

Water Quality Assessment and Genetic Insights into Cyanobacterial Toxin Presence in Gyeonggi Province Reservoirs

This study aimed to examine the water quality of and presence of genes linked to cyanobacterial toxins in 17 reservoirs in Gyeonggi Province, South Korea. The levels of TN, TP, and chlorophyll-a indicated nutrient conditions ranging from eutrophic to hypereutrophic, consistent with international standards. Most reservoirs were found to be vulnerable to algal blooms beyond the eutrophication stage. Chlorophyll-a correlated positively with TP and TOC but negatively with TN in most reservoirs. The mcyA gene for microcystin was detected in 14 reservoirs, with a 64.9% detection rate. The toxin was detected in 47.2% of these cases, with increased concentrations in summer. The dominant microcystin variants were MC-LR>MC-RR>MC-YR. The anaC gene for anatoxin-a was detected in 11 reservoirs at an 18.9% rate, with a toxin detection rate of 9.5%. The aoaB gene for cylindrospermopsin was detected in six reservoirs at a 12.6% rate, although the toxin itself was not detected. This study emphasizes the ongoing presence of cyanobacterial toxin genes and their toxins in Gyeonggi Province reservoirs. The potentially increasing adverse impact of these toxins, because of climate change, needs to be addressed via continuous monitoring and management.

Molecular Genetic Insights into the Stress Responses and Cultivation Management of Zoysiagrass: Illuminating the Pathways for Turf Improvement

Zoysiagrass (Zoysia spp.) and its hybrids are known for their low maintenance requirements and are widely utilized as warm-season turfgrass, which offers considerable ecological, environmental, and economic benefits in various environments. Molecular genetic approaches, including the identification and genetic engineering of valuable gene resources, present a promising opportunity to enhance the quality and performance of zoysiagrass. This review surveys the recent molecular genetic discoveries in zoysiagrass species, with a focus on elucidating plant responses to various abiotic and biotic stresses. Furthermore, this review explores the notable advancements in gene function exploration to reduce the maintenance demands of zoysiagrass cultivation. In addition, we discuss the achievements and potential of contemporary molecular and genetic tools, such as omics approaches and gene editing technologies, in developing zoysiagrass cultivars with desirable traits. Overall, this comprehensive review highlights future strategies that may leverage current molecular insights to accelerate zoysiagrass improvement and further promote sustainable turf management practices.

Transplantation Genetics: The Importance of non-HLA Antibodies, Genetic Insights and Future Perspectives

Solid organ transplantation is an effective and life-saving treatment method for patients with end-stage organ failure. Immunological evaluation is of great importance in the achievement of transplantation, and the determination of HLA incompatibility forms the basis of immunological transplantation success. The presence of donor HLA-related antibodies is known to be asssociated with graft loss and decreased survival rates. However, recent studies have shown clinical and experimental findings related to the important role of non-HLA antibodies in the antibody-mediated rejection and chronic rejection process. The mechanisms triggering auto-antibody production in organ transplantation are an important area of research. These mechanisms stimulate auto-antibody production in the patient causing the expression of organ-origin autoantigens such as ischaemia-reperfusion damage, surgical trauma, alloimmune responses, soluble antigens, extracellular vesicles and apoptotic bodies. In patients with a risk of non-HLA antibody-mediated rejection, there is an urgent need to determine the recipient immunological phenotypes, both for the development of targetted treatments and to increase both graft and patient survival. The aim of this review was to evaluate non-HLA antibody types and their effects on transplantation.

Genetic Insights into Externalizing and Internalizing Traits through Integration of the Research Domain Criteria and Hierarchical Taxonomy of Psychopathology.

There is considerable comorbidity between externalizing (EXT) and internalizing (INT) psychopathology. Understanding the shared genetic underpinnings of these spectra is crucial for advancing knowledge of their biological bases and potential health impacts, and for informing empirical models like the Research Domain Criteria (RDoC) and Hierarchical Taxonomy of Psychopathology (HiTOP). We conducted a multivariate genome-wide association study (GWAS) of EXT and INT psychopathology by applying genomic structural equation modeling to summary statistics from 16 EXT and INT traits in European-ancestry individuals (n = 16,400 to 1,074,629). Downstream analyses explored associations across RDoC units of analysis (i.e., genes, molecules, cells, circuits, physiology, and behaviors). The GWAS identified 409 lead single nucleotide polymorphisms (SNPs) for EXT, 85 for INT, and 256 for EXT+INT (i.e., shared) traits. Bivariate causal mixture models estimated that nearly all EXT and INT causal variants overlapped, despite a genetic correlation of 0.37 (SE = 0.02). Drug repurposing analyses identified potential therapeutic targets, including perturbagens affecting dopamine and serotonin pathways. EXT genes had enriched expression in GABAergic, cortical, and hippocampal neurons, while INT genes were more narrowly linked to GABAergic neurons. EXT+INT liability was associated with reduced grey matter volumes in the amygdala and subcallosal cortex. These findings reveal both genetic overlap and distinct molecular and neurobiological pathways underlying EXT and INT psychopathology. By integrating genomic insights with the RDoC and HiTOP frameworks, this study advances our understanding of the mechanisms driving these dimensions of psychopathology.

Genomic Landscape of Myelodysplastic/Myeloproliferative Neoplasms: A Multi-Central Study.

The accurate diagnosis and classification of myelodysplastic/myeloproliferative neoplasm (MDS/MPN) are challenging due to the overlapping pathological and molecular features of myelodysplastic syndrome (MDS) and myeloproliferative neoplasm (MPN). We investigated the genomic landscape in different MDS/MPN subtypes, including chronic myelomonocytic leukemia (CMML; n = 97), atypical chronic myeloid leukemia (aCML; n = 8), MDS/MPN-unclassified (MDS/MPN-U; n = 44), and MDS/MPN with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T; n = 12). Our study indicated that MDS/MPN is characterized by mutations commonly identified in myeloid neoplasms, with TET2 (52%) being the most frequently mutated gene, followed by ASXL1 (38.7%), SRSF2 (34.7%), and JAK2 (19.7%), among others. However, the distribution of recurrent mutations differs across the MDS/MPN subtypes. We confirmed that specific gene combinations correlate with specific MDS/MPN subtypes (e.g., TET2/SRSF2 in CMML, ASXL1/SETBP1 in aCML, and SF3B1/JAK2 in MDS/MPN-RS-T), with MDS/MPN-U being the most heterogeneous. Furthermore, we found that older age (≥65 years) and mutations in RUNX1 and TP53 were associated with poorer clinical outcomes in CMML (p < 0.05) by multivariate analysis. In MDS/MPN-U, CBL mutations (p < 0.05) were the sole negative prognostic factors identified in our study by multivariate analysis (p < 0.05). Overall, our study provides genetic insights into various MDS/MPN subtypes, which may aid in diagnosis and clinical decision-making for patients with MDS/MPN.

WONOEP appraisal: Genetic insights into early onset epilepsies.

Early onset epilepsies occur in newborns and infants, and to date, genetic aberrations and variants have been identified in approximately one quarter of all patients. With technological sequencing advances and ongoing research, the genetic diagnostic yield for specific seizure disorders and epilepsies is expected to increase. Genetic variants associated with epilepsy include chromosomal abnormalities and rearrangements of various sizes as well as single gene variants. Among these variants, a distinction can be made between germline and somatic, with the latter being increasingly identified in epilepsies with focal cortical malformations in recent years. The identification of the underlying genetic mechanisms of epilepsy syndromes not only revolutionizes the diagnostic schemes but also leads to a better understanding of the diseases and their interrelationships, ultimately providing new opportunities for therapeutic targeting. At the XVI Workshop on Neurobiology of Epilepsy (WONOEP 2022, Talloires, France, July 2022), various etiologies, research models, and mechanisms of genetic early onset epilepsies were presented and discussed.

Microbial degradation of contaminants of emerging concern: metabolic, genetic and omics insights for enhanced bioremediation.

The perpetual release of natural/synthetic pollutants into the environment poses major risks to ecological balance and human health. Amongst these, contaminants of emerging concern (CECs) are characterized by their recent introduction/detection in various niches, thereby causing significant hazards and necessitating their removal. Pharmaceuticals, plasticizers, cyanotoxins and emerging pesticides are major groups of CECs that are highly toxic and found to occur in various compartments of the biosphere. The sources of these compounds can be multipartite including industrial discharge, improper disposal, excretion of unmetabolized residues, eutrophication etc., while their fate and persistence are determined by factors such as physico-chemical properties, environmental conditions, biodegradability and hydrological factors. The resultant exposure of these compounds to microbiota has imposed a selection pressure and resulted in evolution of metabolic pathways for their biotransformation and/or utilization as sole source of carbon and energy. Such microbial degradation phenotype can be exploited to clean-up CECs from the environment, offering a cost-effective and eco-friendly alternative to abiotic methods of removal, thereby mitigating their toxicity. However, efficient bioprocess development for bioremediation strategies requires extensive understanding of individual components such as pathway gene clusters, proteins/enzymes, metabolites and associated regulatory mechanisms. "Omics" and "Meta-omics" techniques aid in providing crucial insights into the complex interactions and functions of these components as well as microbial community, enabling more effective and targeted bioremediation. Aside from natural isolates, metabolic engineering approaches employ the application of genetic engineering to enhance metabolic diversity and degradation rates. The integration of omics data will further aid in developing systemic-level bioremediation and metabolic engineering strategies, thereby optimising the clean-up process. This review describes bacterial catabolic pathways, genetics, and application of omics and metabolic engineering for bioremediation of four major groups of CECs: pharmaceuticals, plasticizers, cyanotoxins, and emerging pesticides.

The aging paradox: integrating biological, genetic, epigenetic, and aesthetic insights into skin aging and non-surgical interventions

The aging paradox: integrating biological, genetic, epigenetic, and aesthetic insights into skin aging and non-surgical interventions

Genomic study of taste perception genes in African Americans reveals SNPs linked to Alzheimer’s disease

While previous research has shown the potential links between taste perception pathways and brain-related conditions, the area involving Alzheimer’s disease remains incompletely understood. Taste perception involves neurotransmitter signaling, including serotonin, glutamate, and dopamine. Disruptions in these pathways are implicated in neurodegenerative diseases. The integration of olfactory and taste signals in flavor perception may impact brain health, evident in olfactory dysfunction as an early symptom in neurodegenerative conditions. Shared immune response and inflammatory pathways may contribute to the association between altered taste perception and conditions like neurodegeneration, present in Alzheimer’s disease. This study consists of an exploration of expression-quantitative trait loci (eQTL), utilizing whole-blood transcriptome profiles, of 28 taste perception genes, from a combined cohort of 475 African American subjects. This comprehensive dataset was subsequently intersected with single-nucleotide polymorphisms (SNPs) identified in Genome-Wide Association Studies (GWAS) of Alzheimer’s Disease (AD). Finally, the investigation delved into assessing the association between eQTLs reported in GWAS of AD and the profiles of 741 proteins from the Olink Neurological Panel. The eQTL analysis unveiled 3,547 statistically significant SNP-Gene associations, involving 412 distinct SNPs that spanned all 28 taste genes. In 17 GWAS studies encompassing various traits, a total of 14 SNPs associated with 12 genes were identified, with three SNPs consistently linked to Alzheimer’s disease across four GWAS studies. All three SNPs demonstrated significant associations with the down-regulation of TAS2R41, and two of them were additionally associated with the down-regulation of TAS2R60. In the subsequent pQTL analysis, two of the SNPs linked to TAS2R41 and TAS2R60 genes (rs117771145 and rs10228407) were correlated with the upregulation of two proteins, namely EPHB6 and ADGRB3. Our investigation introduces a new perspective to the understanding of Alzheimer's disease, emphasizing the significance of bitter taste receptor genes in its pathogenesis. These discoveries set the stage for subsequent research to delve into these receptors as promising avenues for both intervention and diagnosis. Nevertheless, the translation of these genetic insights into clinical practice requires a more profound understanding of the implicated pathways and their pertinence to the disease's progression across diverse populations.

Genomic evaluation for body weight, length and growth estimates in meagre Argyrosomus regius

Meagre (Argyrosomus regius) is a fast-growing sciaenid species which recently received a rising interest in aquaculture diversification and industry sustainability. The present study illustrates the first complete genomic evaluation of meagre for body weight, length and growth parameters using 810 offspring genotyped with a double-digest RAD sequencing approach. Offspring were assigned to both parents using SNP markers and a QTL associated with growth explaining approximately 3.25 % of the phenotypic variance was found. Using pedigree and genomic relationship matrix, moderate to high heritability estimates along with high genetic/genomic correlations between all studied traits were detected with the exception of the initial body weight. The predicted ability of the breeding values was higher using the genomic than the pedigree relationship matrix for body weight and growth. Present findings provide a better genetic insight of the production traits, as well as evidence that the implementation of the genomic information in breeding programs could be beneficial for the parental assignment as well as for the aquaculture production increase through genetic improvement using marker assisted or genomic selection.

Central nervous system pediatric multi-disciplinary tumor board: a single center experience

BackgroundThe Multidisciplinary Tumor Board (MTB) is a collaborative platform involving specialists in oncology, surgery, radiology, pathology, and radiotherapy, and aims to optimize diagnostics and treatments. Despite MTB’s widespread benefits, limited literature addresses its application in pediatric neuro-oncology. After a literature revision on pediatric neuro-oncology MTB, our study describes our institute’s pediatric neuro-oncology MTB, focuses on evaluating its impact and the neuroradiologist’s role in patient-centric approaches, considering recent genetic insights into pediatric brain tumors.Materials and methodsLiterature Review concerning pediatric neuro-oncology MTB from January 2002 to June 2024. Clinical Data: retrospective study of all patient files presented in the pediatric neuro-oncology MTB (pnMTB) between 2019 and 2022. Statistical analysis was mainly carried out by directly comparing the absolute or relative values of the respective parameters examined; qualitative variables compared mainly with the chi-square test, quantitative variables mainly with the t-test.ResultsLiterature Review: 7 papers encompass a multidisciplinary approach for the pediatric CNS tumors.Clinical dataA total of 236 discussions were analyzed representing 107 patients. Median age was 14,3 years (range: 6 months – 17 years). The requests for case evaluations primarily came from the pediatric oncologists (83%) and neurosurgeons (14.8%), and they were mainly addressed to the neuroradiologists (70.3%). Proposals during pnMTB mainly involved imaging follow-up (47.8%) and management with chemotherapy (34.7%). Changes in patient treatment (CPT) occurred in 115 cases, and pediatric neuroradiologist intervention contributed to 72.4% of these changes.ConclusionThanks to their multidisciplinarity, high number of cases discussed, and usual respect for their proposals, the pnMTB has made it possible to improve the coordination among specialties involved in patient management, to apply the recent protocols, and to exchange knowledge among teams managing pediatric CNS tumors.

An accurate haplotyping method using multiplex pyrosequencing with AS-PCR to detect ABCB1 haplotypes associated with rivaroxaban-derived hemorrhagic events

In clinical practice, owing to the comprehensive genetic insights they offer, haplotypes have attracted greater attention than individual single nucleotide polymorphisms (SNPs). Due to the long distances across SNP locations, detecting the haplotype using genomic DNA is challenging. Current haplotyping methods are either expensive and labor-intensive (high-throughput DNA sequencing), or haplotyping a single clinical sample (computational approach) is impossible. Herein, we propose using mRNA as a haplotyping target to minimize the distance among SNPs and employing allele-specific PCR (AS-PCR) to pick up a desired haplotype, followed by multiplex pyrosequencing to type the alleles at the SNP location of interest. AS-PCR was improved by combining an additional 3′-phosphorylated modified probe to achieve the specific separation of two closely similar templates. Only the sample with more than two heterozygotes needs to be haplotyped; therefore, we propose a stratification strategy to screen the samples for further haplotyping. This method was evaluated by associating ABCB1 haplotypes with the rivaroxaban-derived side effect in a cohort of 505 patients with nephrotic syndrome, focusing on the SNPs of ABCB1: rs1236C > T, rs2677G > T/A, and rs3435C > T. We successfully identified five bleeding-related haplotypes: rs1236T-rs2677T-rs3435T, rs1236C-rs2677G-rs3435T, rs1236T-rs2677G-rs3435C, rs1236C-rs2677G-rs3435C, and rs1236T-rs2677T-rs3435C. We compared the results with those from the conventional computational algorithm PHASE and observed that PHASE results dismissed the impact of rs1236C-rs2677G-rs3435C and rs1236C-rs2677G-rs3435T on bleeding risk and erroneously suggested a false positive association of rs1236C-rs2677A-rs3435T with increased bleeding risk.

Genetic insights and clinical implication of inherited hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy is one of the most common inherited genetic diseases of myocardium. It is the leading cause of unexpected mortality among young people and athletes. H.C.M. has been regarded as a sarcomere illness for the past few decades, usually with incomplete penetrance and varied expressivity arising from autosomal dominance. For the purpose of risk and treatment stratification, all diagnostic techniques—such as tissue biopsy, genetic counselling, magnetic resonance imaging, transthoracic and transoesophageal echocardiography, heart catheterization, and genetic counselling—must be used. Additionally, each patient's results should be customized based on their genotype and phenotype. About one-third of people have left ventricular outflow tract blockage at rest, and another third may be prompted to develop it. Interstitial fibrosis and myocyte hypertrophy and disarray are among the histological characteristics of H.C.M. Another common complication of the hypertrophy is left ventricular diastolic dysfunction. The pathogenesis of H.C.M is complex, and its clinical profile is variable. Functional disability resulting from heart failure and stroke (induced by atrial fibrillation) is also attributed to H.C.M. The goal of the current treatments for H.C.M., which include medication, myectomy, alcohol septal ablation, and implanted cardiac defibrillators (I.C.Ds) to avoid SCD, is to slow down the disease's progression and relieve symptoms. Multidisciplinary approaches are best suited for the diagnosis and treatment of patients with H.C.M. More individualized care and better results for this patient population have been made possible by this, as well as the enhanced safety and effectiveness of medicinal, percutaneous, and surgical therapy for H.C.M. In this review the molecular pathophysiology of H.C.M will be reviewed in light of current knowledge. In addition, describing how genetic testing is used for diagnosis and outlining the range of clinical manifestations.

Clinical and Genetic Insights into Desbuquois Dysplasia: Review of 111 Case Reports.

Skeletal disorders encompass a wide array of conditions, many of which are associated with short stature. Among these, Desbuquois dysplasia is a rare but severe condition characterized by profound dwarfism, distinct facial features, joint hypermobility with multiple dislocations, and unique vertebral and metaphyseal anomalies. Desbuquois dysplasia is inherited in an autosomal recessive manner, with both the DBQD1 (MIM 251450) and DBQD2 (MIM 615777) forms resulting from biallelic mutations. Specifically, DBQD1 is associated with homozygous or compound heterozygous mutations in the CANT1 gene, while DBQD2 can result from mutations in either the CANT1 or XYLT1 genes. This review synthesizes the findings of 111 published case reports, including 54 cases of DBQD1, 39 cases of DBQD2, and 14 cases of the Kim variant (DDKV). Patients in this cohort had a median birth weight of 2505 g, a median length of 40 cm, and a median occipitofrontal circumference of 33 cm. The review highlights the phenotypic variations across Desbuquois dysplasia subtypes, particularly in facial characteristics, joint dislocations, and bone deformities. Genetic analyses revealed a considerable diversity in mutations, with over 35% of cases involving missense mutations, primarily affecting the CANT1 gene. Additionally, approximately 60% of patients had a history of parental consanguinity, indicating a potential genetic predisposition in certain populations. The identified mutations included deletions, insertions, and nucleotide substitutions, many of which resulted in premature stop codons and the production of truncated, likely nonfunctional proteins. These findings underscore the genetic and clinical complexity of Desbuquois dysplasia, highlighting the importance of early diagnosis and the potential for personalized therapeutic approaches. Continued research is essential to uncover the underlying mechanisms of this disorder and improve outcomes for affected individuals through targeted treatments.

Associated Factors and Mortality of Arrhythmia in Emergency Department: A Narrative Review.

Cardiac arrhythmias represent a major concern in the emergency department (ED), particularly given their association with significant morbidity and mortality. This narrative review examines the various factors influencing arrhythmias and their impact on patient outcomes in emergency settings. Managing complex supraventricular and ventricular arrhythmias (VAs) during acute myocardial infarction (AMI) and severe cardiovascular conditions remains challenging, despite advancements in diagnostic and therapeutic techniques. Ventricular arrhythmias frequently forecast worse outcomes during hospital stays and heighten the chances of sudden cardiac death and cardiac arrest, especially within the initial 30 days after a heart attack. The incidence of arrhythmias in ED is increasing due to demographic changes and higher rates of chronic illnesses such as diabetes, hypertension, and chronic kidney disease. These comorbidities, coupled with lifestyle factors such as smoking and alcohol consumption, complicate arrhythmia management, especially among older adults and males. Rapid and precise ECG interpretation in the ED is crucial for identifying specific arrhythmia types and initiating appropriate treatments. Atrial fibrillation (AF), the most prevalent form of rapid heart rhythm originating above the ventricles, notably impacts patient outcomes, particularly in cases of AMIand heart failure. In the ED, managing AFfocuses on preventing strokes with thromboprophylaxis and employing risk assessment tools such as CHA2DS2-VASc and HAS-BLED scores. The analysis highlights how risk factors like hypertension, obesity, obstructive sleep apnea (OSA), and diabetes intricately influence the development and worsening of AF. Optimizing AF treatment outcomes requires a multidisciplinary approach involving cardiologists, emergency physicians, and critical care specialists. Future research should prioritize evaluating the effectiveness of preventive and therapeutic interventions for AF, integrating new risk factors and genetic insights to enhance prediction and management strategies. Understanding the factors contributing to arrhythmias and mortality in the ED underscores the importance of timely and accurate diagnostic and therapeutic measures to improve patient care and outcomes.

Uncovering novel regulatory variants in carbohydrate metabolism: a comprehensive multi-omics study of glycemic traits in the Indian population.

Clinical biomarkers such as fasting glucose, HbA1c, and fasting insulin, which gauge glycemic status in the body, are highly influenced by diet. Indians are genetically predisposed to type 2 diabetes and their carbohydrate-centric diet further elevates the disease risk. Despite the combined influence of genetic and environmental risk factors, Indians have been inadequately explored in the studies of glycemic traits. Addressing this gap, we investigate the genetic architecture of glycemic traits at genome-wide level in 4927 Indians (without diabetes). Our analysis revealed numerous variants of sub-genome-wide significance, and their credibility was thoroughly assessed by integrating data from various levels. This identified key effector genes, ZNF470, DPP6, GXYLT2, PITPNM3, BEND7, and LORICRIN-PGLYRP3. While these genes were weakly linked with carbohydrate intake or glycemia earlier in other populations, our findings demonstrated a much stronger association in the Indian population. Associated genetic variants within these genes served as expression quantitative trait loci (eQTLs) in various gut tissues essential for digestion. Additionally, majority of these gut eQTLs functioned as methylation quantitative trait loci (meth-QTLs) observed in peripheral blood samples from 223 Indians, elucidating the underlying mechanism of their regulation of target gene expression. Specific co-localized eQTLs-meth-QTLs altered the binding affinity of transcription factors targeting crucial genes involved in glucose metabolism. Our study identifies previously unreported genetic variants that strongly influence the diet-glycemia relationship. These findings set the stage for future research into personalized lifestyle interventions integrating genetic insights with tailored dietary strategies to mitigate disease risk based on individual genetic profiles.

Genetic Analysis to Estimate Components of Genetic Variances in Indian Mustard (Brassica juncea L.)

The current investigation on Brassica juncea L. genotypes focuses on exploring variations through hybridization to enhance genetic diversity. Additionally, it aims to gather genetic insights into yield and related traits essential for selecting superior varieties in subsequent generations. Using a half diallel design, eight potential genotypes were selected and crossed in every imaginable way. All of the qualities had substantial differences according to analysis of variance; these differences were further examined using Hayman's technique, which revealed that all of the traits are dominated by both additive and dominant gene effects. The findings suggested that dominance and additive genetic variations play a significant role in regulating these features. The magnitude of dominance (H1 and H2) was highly significant higher than additive components (D) for all traits. Positive alleles were not equally distributed among parents (H2/4H1 ≠ 0.25) for all the studied traits. The estimates of environmental variance (E) were significantly positive for all studied traits, except for biological yield per plant suggests that environmental factors exert a notable influence on all examined traits. Narrow sense heritability was less than (0.50) for all traits. The graphical analysis Wr/Vr indicated the importance of over dominance gene effects in controlling all traits. Thus suggesting that selection could be effective in latter generations.

A decision-making framework to maximise the evolutionary potential of populations - Genetic and genomic insights from the common midwife toad (Alytes obstetricans) at its range limits

Anthropogenic habitat modification and climate change are fundamental drivers of biodiversity declines, reducing the evolutionary potential of species, particularly at their distributional limits. Supportive breeding or reintroductions of individuals are often made to replenish declining populations, sometimes informed by genetic analysis. However, most approaches utilised (i.e. single locus markers) do not have the resolution to account for local adaptation to environmental conditions, a crucial aspect to consider when selecting donor and recipient populations. Here, we incorporate genetic (microsatellite) and genome-wide SNP (ddRAD-seq) markers, accounting for both neutral and putative adaptive genetic diversity, to inform the conservation management of the threatened common midwife toad, Alytes obstetricans at the northern and eastern edges of its range in Europe. We find geographically structured populations (n = 4), weak genetic differentiation and fairly consistent levels of genetic diversity across localities (observed heterozygosity and allelic richness). Categorising individuals based on putatively adaptive regions of the genome showed that the majority of localities are not strongly locally adapted. However, several localities present high numbers of private alleles in tandem with local adaptation to warmer conditions and rough topography. Combining genetic diversity and local adaptations with estimates of migration rates, we develop a decision-making framework for selecting donor and recipient populations which maximises the geographic dispersal of neutral and putatively adaptive genetic diversity. Our framework is generally applicable to any species, but especially to amphibians, so armed with this information, conservationists may avoid the reintroduction of unsuitable/maladapted individuals to new sites and increase the evolutionary potential of populations within species.

Germline AIP variants in sporadic young acromegaly and pituitary gigantism: clinical and genetic insights from a Han Chinese cohort.

Variants in the Aryl hydrocarbon receptor-interacting protein (AIP) gene have been identified in sporadic acromegaly and pituitary gigantism, especially in young patients, with a predisposition to aggressive clinical phenotype and poor treatment efficacy. The clinical characteristics of patients with sporadic acromegaly and pituitary gigantism as well as AIP variants in Han Chinese have been rarely reported. We aimed to identify AIP gene variants and analyze the clinical characteristics of patients with sporadic acromegaly and pituitary gigantism in Han Chinese. The study included 181 sporadic acromegaly (N = 163) and pituitary gigantism (N = 18) patients with an onset age of no more than 45 years old, who were diagnosed, treated, and followed up in Huashan Hospital. All 6 exons and their flanking regions of the AIP gene were analyzed with Sanger sequencing or NGS. The clinical characteristics were compared between groups with and without AIP variants. Germline AIP variants were found in 15/181 (8.29%) cases. In patients with an onset age ≤30 years old, AIP variants were identified in 12/133 (9.02%). Overall, 13 variants were detected. The pathogenic (P) variants p.R304X and p.R81X were identified in four cases, with two instances of each variant. Six exon variants (p.C254R, p.K103fs, p.Q228fs, p.Y38X, p.Q213*, and p.1115 fs) have not been reported before, which were likely pathogenic (LP). Patients with P/LP variants had younger onset ages, a higher prevalence of pituitary gigantism, larger tumor volumes, and a higher percentage of Ki-67-positive cells in tumors. In addition, the group with P/LP variants showed a less significant reduction of GH levels in an acute octreotide suppression test (OST) [17.7% (0, 65.0%) vs. 80.5% (63.9%, 90.2%), P = 0.001], and a trend of less GH decrease after the 3-month treatment with long-acting somatostatin analogs (SSAs). Germline AIP variants existed in sporadic Chinese Han acromegaly and pituitary gigantism patients and were more likely to be detected in young patients. AIP variants were associated with more aggressive tumor phenotypes and less response to SSA treatment.

Genetic diversity and epidemiological insights into cutaneous leishmaniasis in Pakistan: a comprehensive study on clinical manifestations and molecular characterization of Leishmania species.

Cutaneous leishmaniasis (CL) stands out as a significant vector-borne endemic in Pakistan. Despite the rising incidence of CL, the genetic diversity of Leishmania species in the country's endemic regions remains insufficiently explored. This study aims to uncover the genetic diversity and molecular characteristics of Leishmania species in CL-endemic areas of Baluchistan, Khyber Pakhtunkhwa (KPK), and Punjab in Pakistan. Clinical samples from 300 CL patients were put to microscopic examination, real-time ITS-1 PCR, and sequencing. Predominantly affecting males between 16 to 30years of age, with lesions primarily on hands and faces, the majority presented with nodular and plaque types. Microscopic analysis revealed a positivity rate of 67.8%, while real-time PCR identified 60.98% positive cases, mainly L. tropica, followed by L. infantum and L. major. Leishmania major (p = 0.009) showed substantially greater variation in nucleotide sequences than L. tropica (p = 0.07) and L. infantum (p = 0.03). Nucleotide diversity analysis indicated higher diversity in L. major and L. infantum compared to L. tropica. This study enhances our understanding of CL epidemiology in Pakistan, stressing the crucial role of molecular techniques in accurate species identification. The foundational data provided here emphasizes the necessity for future research to investigate deeper into genetic diversity and its implications for CL control at both individual and community levels.