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Abstract Background The liver‒brain axis is critical in neurodegenerative diseases (NDs), with lipid metabolism influencing neuroinflammation and microglial function. A systematic investigation of the genetic relationship between lipid metabolism abnormalities and ND, namely, Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS), is lacking. To assess potential causal links between ND and six lipid parameters, two-sample Mendelian randomization (MR) was used. Methods Large-scale European ancestry GWAS data for lipid parameters and ND (AD, ALS, PD, and MS) were used. Genetic variants demonstrating significant correlations (P

Abstract Genetic diversity is crucial to secure the survival and sustainability of ecosystems. Given anthropogenic pressure, as well as the projected alterations connected with the level and circulation of water, riparian forests are of particular concern. In this paper, we assessed the genetic variation of black poplar – one of the keystone tree species of riverine forests. The natural habitats of black poplar have been severely transformed leading to a significant decline of its population size. Using a set of 18 nuclear microsatellites and geographic location data, we studied 26 remnant populations (1,261 trees) located along the biggest river valleys in Poland. Our main goal was to assess the overall genetic variation and to verify if range fragmentation and habitat transformation have disrupted gene exchange among populations. Genotyping revealed that 261 trees were clones. The level of clonality was higher in more transformed river sections. All populations have probably gone through a drastic genetic bottleneck in the distant past, and most of them have low effective population sizes. Still, the overall level of genetic variation remains high, but certain populations require attention due to their lower genetic variation, higher clonality and strong spatial genetic structure. Genetic differentiation was low, yet Bayesian clustering supported the existence of 11 genetic clusters. According to the results, gene exchange is most prevalent between adjacent populations. Relatively free gene flow occurs only along the Vistula, particularly in its middle section which is characterized by the highest genetic variation. Noticeable genetic structuring was observed along the Oder. Populations located at the range margin showed signs of genetic divergence and reduction of variation. We conclude that human activities have impacted the gene pool of black poplar in Poland by disrupting landscape connectivity and preventing the species from generative reproduction. The study provides practical guidelines on how to develop and implement the conservation program for the gene pool of black poplar in Poland. It also presents a strong case favoring river renaturation and genetic monitoring, particularly concerning keystone species.

Mendelian randomization (MR) is a statistical method that uses genetic variants as instrumental variables to estimate the causal effect of exposure on an outcome in the presence of unmeasured confounding. In this review, we argue that it is crucial to acknowledge the instrumental variable assumptions in MR analysis. We describe widely used MR methods, using an example from obesity-related metabolic disorders. We describe situations in which instrumental variable assumptions are violated and explain how to evaluate these violations and employ robust methods for accommodating such violations.

Abstract The liverwort Arnellia fennica has a circumarctic distribution with disjunct and scarce localities in the Alps, Carpathians, and Pyrenees. Within the Carpathians, it is only known from the Tatra Mountains (in Poland), where so far only four occurrences have been documented in the forest belt of the limestone part of the Western Tatras. The species is considered a tertiary relict, which owes its survival during the last glaciation period to low-lying locations in areas not covered by ice. Previously, it has been demonstrated that this plant does not produce gemmae in the Tatra Mountains, nor does it reproduce sexually, hence it has not spread in this massif despite the high availability of potential habitats. These studies address the following questions: (1) why A. fennica, an arctic-alpine species, has only been found at low elevations in the Tatra Mountains so far, (2) what were the possibilities of its survival during the glaciation period as verified based on the latest paleoglaciological map, (3) how this species persists in the Tatras and why it remains a rare plant. As a result, nine additional new occurrences were found, bringing the total to 13 throughout the massif. Some of the sites were found in the high mountain area. For the first time, the production of gemmae in the Tatra population of A. fennica was observed and documented, along with the presence of male specimens of this dioecious species. Genetic studies have shown that individuals from all three groups of sites are genetically homogeneous, indicating a lack of sexual reproduction. The only way of dispersal for A. fennica in the Tatras is through propagule production. The uniqueness and specificity of these structures have been described, which differ significantly from the common model known in liverworts. The rarity of the species in the Tatra massif is attributed to the inefficient mode of vegetative reproduction and the absence of sexual reproduction. Paleoglaciological analysis of all montane sites (historical and new) of A. fennica showed that half were located in areas covered by glaciers. The hypothesis of this liverwort’s survival during the glaciation period, at lower elevations, should be rejected. In light of the new data obtained, montane localities should be considered as secondary, which could have arisen after the glacier retreated only from high-mountain populations producing propagules transported downhill.

Abstract Tor putitora is an endangered cyprinid fish constrained to cold water and is also considered an indicator of a healthy aquatic ecosystem. The present study aimed to examine the haplotypic diversity, genetic variation and population structure of T. putitora isolates using COI and Cyt b gene sequences submitted in GenBank. Bioinformatic analysis was carried out using 106 COI and 183 Cyt b gene sequences as well as 2 reference genome sequences. Analysis of COI and Cyt b gene reveals 18 and 85 haplotypes respectively. Mutation was observed at 44 different sites in COI and 173 in Cyt b gene sequences. Haplotype 4 and haplotype 37 were considered ancestral in COI and Cyt b respectively. Analysis of COI gene reveals moderate haplotype diversity (0.630) and low Nucleotide diversity (0.00662) whereas Cyt b has higher haplotype diversity (0.804) and low Nucleotide diversity (0.00582). Moreover, the neutrality test such as Tajima’s D, and Fu’s Fs showed negative values in both gene sequences, suggesting population expansion attributed to habitat destruction. So, comprehending the genetic variability within and among the T. putitora population is crucial for conserving and managing this species. Integration of genetic diversity into conservation planning can enhance the effectiveness of breeding programs and habitat restoration efforts.

We have developed a dual base editor, rA&GBE, by fusing adenine and glycosylase base editors. It can induce up to eight types of mutations in T0-generation rice, including single-base conversion, simultaneous multiple-base conversions, and InDels, using a single guide RNA. A-to-G and C-to-G/T conversions occur simultaneously on the same DNA strand. The rA&GBE system may prove useful for crop improvement and in planta direct evolution.

Objective·To explore the correlation between the genetic variations rs7305526 and rs11615756 of nitric oxide synthase 1 (NOS1) and the human sleep traits, including insomnia, sleep duration, and clinical quantitative traits related to obstructive sleep apnea (OSA).Methods·The NOS1 gene expression pattern at the whole-brain level using the Allen Human Brain Atlas dataset was analyzed. Subsequently, we performed expression quantitative trait locus (eQTL) analysis to investigate the impact of rs7305526 and rs11615756 on NOS1 gene expression. Regression analysis was conducted to assess the associations between rs7305526 and rs11615756 with insomnia and sleep duration based on the United Kingdom Biobank (UKB) Genome-Wide Association Study (GWAS) dataset. Furthermore, we explored the relationships between rs7305526 and rs11615756 with clinical quantitative traits of OSA, such as respiratory events, oxygen levels, and sleep traits, using clinical monitoring data from the Shanghai Sleep Health Study Cohort (SSHS) based on standard polysomnography (PSG).Results·The NOS1 gene demonstrated elevated levels of expression in various brain regions crucial for regulating sleep, namely the amygdala, basal forebrain, striatum, and thalamus, as well as in the respiratory center, including the mesencephalon and pontine tegmentum. In contrast, the expression level of NOS1 gene was significantly reduced or absent in areas such as the cerebral cortex and cerebellum. Variants rs7305526 and rs11615756 were significantly negatively correlated with the expression levels of NOS1 in the cerebral cortex. Additionally, rs11615756 was also significantly negatively correlated with the expression level of NOS1 in the amygdala. Analysis of the UKB GWAS data revealed that the variant rs7305526 was not significantly associated with either insomnia or sleep duration, while rs11615756 demonstrated a noteworthy negative correlation specifically with sleep duration. Data obtained from the SSHS indicated a significant association between rs7305526 and alterations in clinical quantitative traits of OSA, including lowest pulse blood oxygen saturation (LSpO2), apnea-hypopnea index (AHI), and the ratio of non-rapid eye movement (NREM) stage 2 sleep duration. Although rs11615756 showed a notable negative correlation solely with the quantity of NREM stages 2 and 3, both rs11615756 and rs7305526 showed significant correlations with some respiratory events and oxygen traits after stratification according to the severity of OSA.Conclusion·Genetic variants of NOS1 gene are respectively associated with human sleep duration traits and OSA-related variables, suggesting that NOS1 gene plays a crucial regulatory role in human sleep and clinical quantitative traits of OSA. The regulation of sleep traits by rs7305526 (C>A) is independent of its regulation of respiratory events and oxygen traits.

Necrobia rufipes (Coleoptera: Cleridae) are economically essential since most species are predaceous on other insects in both adult and larval stages. Molecular investigation is useful for identifying species and other downstream analysis. In addition to identification, this research addresses past gaps in knowledge through establishing the sequence of current insect COX genes and other investigations. A novel method was developed in this study to examine COX gene sequencing and to determine the relationship between Cleridae subfamilies. The DNA was isolated, and a band of 550 bp of the mt COX gene was amplified. Then the amplicons were sequenced. Parts of the COX gene were aligned with Clustal Omega and visualized and edited via Jalview software. This research presented the Ts:Tv mutation ratio through a sequencing technique for the species with reliable results. The species from the Kurdistan region in this study were clustered in a monophyletic clade published in Germany (KU916741.1) with a high identity value (100%). The COI sequence of the species was submitted to GenBank with the PP175929.1 accession number. The base composition of the COX gene sequence had a higher AT figure at 67.89% compared to the GC’s 32.1%. These results offer new valuable insights on the Necrobia rufipes and may provide useful data for its identification, bioinformatics uses, and management applications. The results show that the mt-COX can be used as a marker for further molecular experiments.

Abstract Background Topical tacrolimus has been used as one of the treatment options for atopic dermatitis (AD). A burning sensation is the most common side effect of topical tacrolimus. Objectives This study was designed to identify genetic variations and clinical features to predict burning sensation by topical tacrolimus in patients with AD. Methods Patients with AD who had applied topical tacrolimus were classified according to the presence of a burning sensation. We compared the patients' demographics and blood test results, including serum eosinophil, serum immunoglobulin E and multiple allergen simultaneous test. Furthermore, the frequency of variations in barrier‐ (KLK7, FLG 3321delA, FLG K4022X, SPINK5 1156, SPINK5 1188, SPINK5 2475) and immune response‐ (DEFB1, KDR, CDKAL1, IL‐5RA, IL‐9, IL‐12RB1, IL‐12RB2, IL‐17RA) related genes was compared between two groups by reverse blot hybridization assay of the buccal mucosa. Results Among 206 patients with AD using topical tacrolimus, 34 (16.5%) complained of a burning sensation. The burning sensation was associated with severe AD and a family history of atopic disease. Furthermore, with statistical significance, a heterozygous mutation in the filaggrin gene (FLG K4022X) was more frequent in AD patients with a burning sensation due to topical tacrolimus. However, no other significant genetic differences were observed between them. Conclusions A burning sensation caused by topical tacrolimus can be expected in AD patients with severe symptoms, a family history of atopy and a genetic variation such as FLG K4022X.

Mango stands as a critical tree crop with significant economic value on a global scale. This is attributed to the advantageous effects of its mineral content, abundance of vitamins, and biologically active compounds, all of which contribute to the overall health and well-being of consumers. Therefore, it needs special attention for its emergence through the phenotypic characterization of the existing varieties. To do this, we characterized agro-morphologically different mango varieties in some parts of Nigeria. Thus, the objective of this study was to analyze the genetic variation and morpho-agronomic traits of different mango varieties in Nigeria. Qualitative and quantitative data from mango leaves were recorded from 10 mature leaves and mango fruits in 4 States of different agroecological zones of Nigeria. The genetic variability, phenotypic and genotypic variances, coefficients of genotypic and phenotypic variation, broad sense heritability, and genetic advance, based on morpho-agronomic traits, were evaluated. Analysis of variance and descriptive analysis through the coefficient of variability revealed an extensive diversity and the prospect of genetic selection for profitable characters. Broad sense heritability for all the characters varied from 44.61% for petiole length to 98.48% for pulp weight and fruit weight, indicating moderate to high inheritability. Genetic advance as a percentage of the mean (GAM) was high in all the traits studied and ranged from 28.27% to 172.58%. The phenotypic coefficient of variation (PCV) was greater than the genotypic coefficient of variation (GCV), demonstrating the extent of environmental effects. Edible rate is significantly and positively corrected with fruit length, fruit width, fruit weight, peel weight, pulp weight, seed length, seed width, pulp%, and pulp thickness.

Abstract Background Aneuploidy in plants commonly presents as large variations in morphology, physiology, biochemistry, and genetic effects owing to its karyotypic imbalance. Results In this study, the trait variations of 393 offspring obtained by pollinating Populus alla × Populus glandulosa ‘YXY 7’ (2n = 2x = 38) with Populus ‘Beilinxiongzhu 1#’ (2n = 3x = 57) were explored. The results showed several morphological variations in the cotyledons, including two (69.68%), three (24.07%), and four cotyledons (6.25%). Additionally, the progeny exhibited extensive segregation of ploidy levels, ranging from 38 to 74. Furthermore, seedlings with different chromosome numbers varied in growth traits and physiological activities during growth and development. The backcross progeny with 51–60 chromosomes had a significantly larger basal diameter and seedling height than those with other chromosome numbers. The phenotypic correlations between the traits indicated that the dose effect of the chromosomes significantly affected the basal diameter, petiole length, and leaf length, particularly with stomatal length and stomatal density. Weak and negative estimated correlations were observed between the physiological traits associated with photosynthesis and most of the studied traits. Conclusions This study provides new genetic material with different chromosome compositions, which will contribute to analyzing chromosomal function and integrate the variations in chromosomal dosage into Populus breeding programs.

Abstract Background Several blood proteins might be associated with the development of colorectal cancer (CRC), but many studies on this topic are often biased. By using genetic variation data, which is less influenced by environmental factors, we can better determine the causal relationship between specific blood proteins and the occurrence of colorectal cancer. Methods Data from a genome-wide association study (GWAS) on blood proteins, encompassing 1,478 proteins, and colorectal cancer (CRC) GWAS data, covering 637,693 subjects, were collected and organized. Additionally, GWAS data for obesity, diabetes mellitus (DM), and smoking were obtained for further analysis. Single nucleotide polymorphisms (SNPs) significantly associated with the exposure factors (blood proteins) were selected to ensure their independence from other confounding factors and outcomes (CRC onset), and that they only affected outcomes through blood proteins. The causal effects of Mendelian Randomization (MR) were primarily estimated using the inverse variance weighted (IVW) method, with other methods serving as supplementary approaches. The Cochran's Q-test assessed heterogeneity among SNP estimates; the MR Egger method evaluated pleiotropy; and the leave-one-out test examined the sensitivity of individual SNPs. Obesity, DM, and smoking were included in the multivariate MR analysis. Result A total of 31 SNPs and 8 blood protein exposure factors were identified, specifically TNFRSF16 (4 SNPs), RNF8 (4 SNPs), MRM3 (4 SNPs), ST6GALNAC1 (4 SNPs), TIE1 (4 SNPs), CBP (4 SNPs), DNAJB9 (4 SNPs), and EDN2 (3 SNPs). The IVW results showed a significant causal relationship between all 8 exposure factors and colorectal cancer (P

Abstract Background Immune factors are crucial in the pathogenesis of rheumatoid arthritis (RA), and immune cells play a key role in the development of RA. However, there is still disagreement regarding the specific roles of each type of immune cell in the pathological process of RA. Methods This study used bidirectional two-sample Mendelian randomization (MR) analysis to determine the causal relationship between immune cell characteristics and RA. Utilizing publicly available genetic data, we initially treated immune cell characteristics as exposures to investigate their causal effects on the risk of RA. Subsequently, we performed reverse two-sample MR using the positively selected cells from the initial analysis as outcomes, aiming to identify the core immune cells involved. Finally, a comprehensive sensitivity analysis was conducted to validate the robustness, heterogeneity, and horizontal pleiotropy of the results. Results Using data from 731 immune cells as exposures and cell SNPs as instruments, we independently conducted two-sample MR analysis for each patient with RA. The main analytical method used was the IVW method, with a significance level set at P

Abstract Environmental risk assessment (ERA) is critical for protecting life by predicting population responses to contaminants. However, routine toxicity testing often examines only one genotype from surrogate species, potentially leading to inaccurate risk assessments, as natural populations typically consist of genetically diverse individuals. To evaluate the importance of intraspecific variation in translating toxicity testing to natural populations, we quantified the magnitude of phenotypic variation between 20 Daphnia magna clones exposed to two levels of microcystins, a cosmopolitan cyanobacterial toxin. We observed significant genetic variation in survival, growth, and reproduction, which increased under microcystins exposure. Simulations of survival showed that using a single genotype for toxicity tolerance estimates on average failed to produce accurate predictions within the 95% confidence interval over half of the time. Whole genome sequencing of the 20 clones tested for correlations between toxicological responses and genomic divergence, including candidate loci from prior gene expression studies. We found no overall correlations, indicating that clonal variation, rather than variation at candidate genes, predicts population-level responses to toxins. These results highlight the importance of incorporating broad intraspecific genetic variation, without focusing specifically on variation in candidate genes, into ERAs to more reliably predict how local populations will respond to contaminants.

Abstract Background and aim Recurrent pregnancy loss (RPL), also known as recurrent implantation failure (RIF), is a distressing condition affecting women characterized by two or more consecutive miscarriages or the inability to carry a pregnancy beyond 20 weeks. Immunological factors and genetic variations, particularly in Vit D Binding Protein (VDBP), have gained attention as potential contributors to RPL. This study aimed to provide insight into the immunological, genetic, and metabolic networks underlying RPL, placing a particular emphasis on the interactions between VDBP, HLA-G1, CTLA-4, ENTPD1, and adenosine-fetal-maternal conflict crosstalk. Methods A retrospective study included 198 women with three or more consecutive spontaneous abortions. Exclusion criteria comprised uterine abnormalities, endocrine disorders, parental chromosomal abnormalities, infectious factors, autoimmune diseases, or connective tissue diseases. Immunological interplay was investigated in 162 female participants, divided into two groups based on their Vit D levels: normal Vit D-RPL and low Vit D-RPL. Various laboratory techniques were employed, including LC/MS/MS for Vit D measurement, ELISA for protein detection, flow cytometry for immune function analysis, and molecular docking for protein–ligand interaction assessment. Results General characteristics between groups were significant regarding Vit D and glucose levels. Low Vit D levels were associated with decreased NK cell activity and downregulation of HLA-G1 and HLA-G5 proteins, while CTLA-4 revealed upregulation. VDBP was significantly downregulated in the low Vit D group. Our findings highlight the intricate relationship between Vit D status and adenosine metabolism by the downregulation of SGLT1, and NT5E, key components of adenosine metabolism, suggests that Vit D deficiency may disrupt the regulation of adenosine levels, leading to an impaired reproductive outcome. HNF1β, a negative regulator of VDBP, was upregulated, while HNF1α, a positive regulator, was downregulated in low Vit D women after RPL. Molecular docking analysis revealed crucial residues involved in the interaction between Vit D and HNF1β. Conclusion Collectively, these findings underscore the importance of Vit D in modulating immune function and molecular pathways relevant to pregnancy maintenance, highlighting the need for further research to elucidate the mechanisms and potential therapeutic interventions for improving pregnancy outcomes in individuals with Vit D deficiency and RPL.

Background Migraine belongs to the group of primary headaches, affecting 14.4% of the global population. The pathophysiological mechanisms of migraine involve the interplay between hypothalamic activation, cortical spreading depression, trigeminal stimulation, and inflammatory components with neurogenic inflammation or neuroinflammation.

In this study, genome-wide variability and selection signatures in Kangal Akkaraman sheep were assessed by 238.103 bi-allelic single nucleotide polymorphisms (SNPs) recovered from genotyping-by-sequencing (GBS) libraries processed in Illumina HiSeq X Ten instrument. Summary statistics of genetic diversity such as minor allele frequency (MAF), observed (HO) and expected (HE) heterozygosity were estimated at 0.32, 0.29, and 0.30, respectively. A declining trend in effective population size was observed through generations in which the current population was estimated at 978 individuals 150 generations ago. 608 of 647 runs of homozygosity (ROH) islands were classified into ≤2 Mb. Strong selection signals were identified in thirteen genomic intervals overlapped with 17 protein-coding genes. The sheep quantitative trait locus (QTL) database confirmed that these genomic regions were associated with economically important traits such as milk content (KCNH5, KCNH7, LRP1B, SNAPC1, and SYT16) and fleece yield (CCDC85A, EFEMP1, and PPP4R3B), parasite resistance (MMS22L and KLHL32), fat deposition in the tail (JAZF1, TAXIBP1, EVX1, and HOXA13), and water-holding capacity (KLHL1 and DACH1). This study implies that the Kangal Akkaraman sheep will play a vital role in developing some genotypes tolerant to environmental challenges, parasite infections, fat deposition, and water-holding capacity in the future. Still, the other native sheep should be screened to identify genomic regions under selection practices using high-density genetic data obtained from next-generation sequencing (NGS) platforms.

Abstract Background Populations of Olea europaea subsp. europaea var. sylvestris, the ancestor of cultivated olives, are scattered across the Mediterranean Basin. However, after millennia of possible hybridization with cultivated varieties, the genetic identity of many of these populations remain questionable. In the southern Levant, the plausible primary domestication center of olives, many of the naturally growing olive (NGOs) are considered feral, having developed from nearby olive groves. Here, we investigated the genetic identity of NGOs population in the Carmel region, hypothesizing that their specific location, which limit anemophily, provided an opportunity for the persistence of genuine var. sylvestris. Results We mapped more than 1,000 NGOs on the Kurkar ridge along the Carmel coast, within and outside the residential area of Atlit and used simple sequence repeats of 14 loci to assess the spatial genetic structure of 129 NGOs. Genetic diversity parameters and genetic distances between NGO and cultivated olives, as well as phenotypic and morphometric analyses of their oil content and pits, respectively, indicated the presence of a genuine var. sylvestris population. However, NGOs within the residential area of Atlit and old settlements showed an intermediate admix genetic structure, indicating on hybridization with local varieties, a consequence of their proximity to cultivated trees. Conclusions Integrating the results of genetic and phenotypic analyses we provide crucial evidence of the presence of a genuine var. sylvestris population in the southern Levant, in close geographical proximity to archaeological sites with the earliest evidence of olive exploitation in the ancient world. We supplement the results with recommendations for a conservation program that combines municipal requirements and the urgent need to preserve the largest population of var. sylvestris in the southern Levant.

Genetic variation is one of the important factors leading to the incidence and development of cancer. Copy number variation is an important source of genetic diversity， which can be expressed as gene amplification or deletion in structure， and is related to the occurrence and development of different tumors. High-throughput sequencing and gene chip technology can be adopted to detect the variation of copy number， and provide relevant information about tumor molecular characteristics， prognosis and treatment， which is conducive to more accurate diagnosis and treatment decisions for patients in clinical practice. Ovarian cancer is one of the female reproductive system diseases with the highest mortality rate. Understanding its pathogenesis is of significance for improving the survival rate of ovarian cancer. At present， the specific role and mechanism of copy number variation in ovarian cancer are still unclear. In this article， relevant copy number variation in ovarian cancer was reviewed based on the existing research results， aiming to provide novel ideas and methods for the prevention， diagnosis and treatment of ovarian cancer.

OBJECTIVE: To conduct clinical and genetic analysis in a patient with severe combined immunodeficiency disease (SCID). METHODS: A 3.5-year-old female patient with chronic diarrhea, fever, and failure to thrive was examined at the Pakistan Institute of Medical Sciences, Islamabad. Ethical approval was obtained, and informed consent was secured for genetic studies. Flow cytometry was performed on blood samples to evaluate T, B, and NK cell concentrations. Genomic DNA was extracted from peripheral blood samples of the patient, her mother, and healthy siblings. Sanger sequencing of the RAG1 gene was conducted, followed by mutational analysis using BioEdit and bioinformatics tools for pathogenicity assessment. RESULTS: The proband, the youngest girl born to first-cousin parents presented with intractable diarrhea with failure to thrive and skin and nappy rashes on clinical evaluation. The immunological assessment revealed total absence of B and T lymphocytes, normal NK cells (47% with 85% CD16 and CD56 respectively: No CD4, CD8 and CD19), and significant hypogammaglobulinemia (IgG;165 mg/dl, IgM; 9 mg/dl, IgA;8 mg/dl), while normal level of IgE (2 mg/dl). On the other hand, targeted Sanger sequencing of RAG1 exon 2 region revealed a new homozygous deleterious mutation (NM_000448.2: c.2876 G>A; p.Trp959*) in the RAG1 gene resulting in complete loss of function due to the production of truncated protein. CONCLUSION: We identified a potentially pathogenic nonsense mutation in the RAG1 gene (c.2876 G>A; p.Trp959*) in a child with SCID. This finding emphasizes the significance of early detection for timely treatment and genetic counseling.

Background. Fresh pasta filata cheese is considered as one of the most important foods in the Venezuelan diet. It is typically produced by small-scale producers using raw milk. The objective of this research was to molecularly characterize the pathogenic potential of Escherichia coli strains isolated from pasta filata cheese manufactured and marketed in Venezuela. Methodology. In the period between January and March of 2019, a total of 36 strains of E. coli were isolated from a variety of pasta filata cheeses including 17 samples of mozzarella, 16 of telita, and 3 of guayanés. These strains were isolated according to the Venezuelan Commission of Industrial Standards (COVENIN) and identified by conventional methods (biochemical and phenotypic tests). Antimicrobial susceptibility was determined using the disk diffusion technique. Phylogenetic grouping and detection of virulence genes were performed by Polymerase Chain Reaction amplification. Diversity and genetic relationships were determined by Rep-PCR. Results: All strains were susceptible to the tested antibiotics. Phylogroup A (n=19) was the most frequent (52.8%), followed by groups D (n=11; 30.6%), and B1 (n=2; 5.6%). The majority of isolates carried at least two virulence genes, one coding for adhesion mechanisms (fimH) and the other for iron uptake (fyuA). Only one strain of phylogroup A presented a profile consisting of four virulence genes (fimH, fyuA, kpsMT II, and papAH). Four strains that could not be classified according to Clermont's scheme carried resistance genes as well. A heterogeneous population structure was observed by Rep-PCR of the strains. Conclusion: Results support the hypothesis that the E. coli strains isolated from the three types of pasta filata cheeses manufactured and marketed in Venezuela have identical characteristics and virulence factors to Extraintestinal Pathogenic E. coli strains observed in animals and humans, posing a potential health risk. Therefore, it is essential to improve hygienic and sanitary controls at all stages of cheese production and to implement measures for epidemiological surveillance of potentially pathogenic bacterial strains present in Venezuelan, artisanal pasta filata cheeses. DOI: 10.18502/jfqhc.11.3.16589

Identifying the best genetic material across provenances and genotypes, particularly for vigorous seedling production, is a key aspect of domestication programs. This study aimed to (i) assess provenance and tree-to-tree differences in the germination performance of Balanites aegyptiaca and (ii) identify mother trees with the best germination performance for seed sourcing. A total of 1440 ripe fruits were collected from 36 mother trees in two provenances (Karimama and Tanguieta) in Benin and one provenance (Mouhoun) in Burkina Faso. A germination trial was conducted using a split-plot design over 30 days. Differences among provenances and trees were assessed based on three metrics of germination performance: final germination percentage (FGP), mean germination time (MGT), and germination index (GI), using generalized linear models and linear mixed-effects models. Phenotypic variability, heritability, and genetic advance of B. aegyptiaca based on these metrics were further evaluated. Results showed that FGP, MGT, and GI varied significantly among provenances. FGP and GI exhibited considerable variation among provenances (44.7 and 38.9 %, respectively) and among mother trees (48.2 and 46.7 %, respectively). High phenotypic coefficient of variation (> 67 %), genotypic coefficient of variation (> 63 %), broad-sense heritability (> 80 %), and genetic gain (> 100 %) were observed for FGP and GI, indicating significant additive genetic effects for these metrics. Eight mother trees from Mouhoun, four from Karimama, and four from Tanguieta were identified as the best performers based on final germination percentage. Our study showed that selection based on FGP and GI can be used to identify elite genotypes for domestication and improvement programs for B. aegyptiaca.

ABSTRACT The evolving threat of new pathogen variants in the face of global environmental changes poses a risk to a sustainable crop production. Predicting and responding to how climate change affects plant‐pathosystems is challenging, as environment affects host–pathogen interactions from molecular to the community level, and with eco‐evolutionary feedbacks at play. To address this knowledge gap, we studied short‐term within‐host eco‐evolutionary changes in the pathogen, Xanthomonas perforans, on resistant and susceptible pepper in the open‐top chambers (OTCs) under elevated Ozone (O3) conditions in a single growing season. We observed increased disease severity with greater variance on the resistant cultivar under elevated O3, yet no apparent change on the susceptible cultivar. Despite the dominance of a single pathogen genotype on the susceptible cultivar, the resistant cultivar supported a heterogeneous pathogen population. Altered O3 levels led to a strain turnover, with a relatively greater gene flux on the resistant cultivar. Both standing genetic variation and de novo parallel mutations contributed toward evolutionary modifications during adaptation onto the resistant cultivar. The presence of elevated O3, however, led to a relatively higher genetic polymorphism, with random and transient mutations. Population heterogeneity along with genetic variation, and the promotion of interdependency are mechanisms by which pathogen responds to stressors. While parallel mutations may provide clues to predicting long‐term pathogen evolution and adaptive potential. And, a high proportion of transient mutations suggest less predictable pathogen evolution under climatic alterations. This knowledge is relevant as we study the risk of pathogen emergence and the mechanisms and constraints underlying long‐term pathogen adaptation under climatic shifts.

ABSTRACT Significant genetic differentiation between Symbiodiniaceae populations in coral hosts can be induced by a range of factors including geography, latitude, depth, temperature and light utilisation. The conventional method of measuring Symbiodiniaceae diversity involving the ITS2 region of rDNA has several limitations, stemming from insufficient genetic resolution and the multi‐copy nature of the marker. This could be improved by using higher throughput whole genome sequencing to identify fine‐scale population genetic differences and provide new insight into factors influencing coral‐Symbiodiniaceae associations. The aim of this study was to investigate the genetic diversity of Symbiodiniaceae populations using low‐coverage whole genome sequencing in sympatric populations of Acropora cf. secale and allopatric populations of Acropora millepora that reproduce in different seasons in Western Australia. Genetic diversity of Symbiodiniaceae populations in these two species was examined using principal coordinates analysis and permutational analysis of variance. This analysis revealed that while all colonies were dominated by Cladocopium, there was a significant genetic difference between Symbiodiniaceae populations in both species. In A. millepora, this variation could be due to the latitudinal variation between populations or differences in reproductive seasonality, but in sympatric populations of A. cf. secale, genetic differences between Symbiodiniaceae populations were clearly aligned with the reproductive seasonality of the coral host. The use of whole genome sequencing improved the sensitivity to detect Symbiodiniaceae genetic population structure between coral populations, which increases our ability to identify genetic and potentially functional differences associated with variation in Symbiodiniaceae populations.

Background Camellia nitidissima var. phaeopubisperma is a variety in the section Chrysantha of the genus Camellia of the family Theaceae which is native to Fangchenggang, Guangxi, China. To date, the genetic diversity and structure of this variety remains to be understood. Methods In the present study, eight simple sequence repeat (SSR) molecular markers previously screened were used to analyze the genetic diversity and structure of C. nitidissima var. phaeopubisperma natural populations from 14 growing areas in China, so as to determine the influence of environmental changes on genetic variations and provide the basis for introduction and selection of suitable growing sites of that variety. Results Our results show that, for the eight SSR loci, the observed numbers of alleles per locus (Na) and the effective numbers of alleles per locus (Ne) were nine and 3.206, respectively on average, and the Ne was lower than the Na for all loci; the observed heterozygosity (Ho) was lower than the expected heterozygosity (He). For all the eight loci, the fixation index (F) was greater than 0, and the intra-population inbreeding coefficient (Fis) for seven loci was positive. Three loci were moderately polymorphic (0.25 < polymorphism information content (PIC) 0.5); all eight loci had a moderate genetic differentiation level (0.05 < genetic differentiation coefficient (Fst)

ObjectiveThis research intends to examine the clinical characteristics and genetic diversity of a child experiencing epilepsy with myoclonic-atonic seizures (EMAS) attributed to a variant in the SLC6A1 gene.MethodsA male child diagnosed with EMAS underwent clinical and electroencephalographic evaluation. Peripheral blood samples were collected for DNA extraction and subsequent whole-exon gene sequencing. For previously identified patients, high-throughput sequencing was utilized, whereas Sanger sequencing was employed for the parents to determine the site of the gene mutation and examine the connection between genotype and phenotype.ResultsThe male child showed delays in intellectual and language development before the disease began. At 1 year and 2 months, he had a febrile seizures, which was succeeded by seizures at 2 years and 9 months; these seizures presented as generalized tonic-clonic, myoclonic, and myoclonic-atonic seizures, along with symptoms showing inattention and hyperactivity. After receiving treatment with levetiracetam (50 mg·kg·d−1), the child has been free of seizures for the last 8 months. Genetic analysis indicated a heterozygous missense variant of c.263T > C (p.L88P) in the SLC6A1 gene in the child, recognized as a spontaneous mutation that has not been previously documented in the literature.ConclusionThe variant in the SLC6A1 gene is implicated as one of the etiological factors contributing to EMAS coupled with neurodevelopmental abnormalities. The identification of this novel mutation enriches the spectrum of known SLC6A1 gene variants.

IntroductionSorghum bicolor: widely cultivated in Asia and Africa, faces increasing challenges from climate change, specifically from abiotic stresses like drought and salinity. This study evaluates how different sorghum genotypes respond to separate and combined stresses of drought and salinity.MethodsCarried out with three replications using a randomized complete block design, the experiment measured biochemical and physiological parameters, including stomatal conductance, chlorophyll content, and antioxidant enzyme activities. Molecular analysis focused on stress-responsive gene expression.ResultsResults indicated enhanced stress responses under combined conditions, with significant variation in antioxidant enzymatic activities among genotypes. Genotype-specific osmotic adjustments were observed through proline and glycine betaine accumulation. Physiological parameters such as chlorophyll content, cell membrane stability, stomatal conductance, and water potential were critical indicators of stress tolerance. Gene expression analysis revealed upregulation of stress-responsive genes, particularly under combined stress conditions.DiscussionCorrelation and principal component analysis analyses highlighted the interdependencies among traits, emphasizing their roles in oxidative stress mitigation. Samsorg-17 exhibited the highest resilience due to consistently high levels of catalase, superoxide dismutase, and glycine betaine, alongside superior physiological attributes. CRS-01 showed moderate resilience with the highest Na/K ratio and notable photosynthesis rate and relative water content, but was less consistent in biochemical markers under stress. Samsorg-42 demonstrated resilience under specific conditions but was generally less robust than Samsorg-17 across most indicators. These findings emphasize the importance of developing stress-resilient sorghum cultivars through targeted breeding programs to enhance tolerance to drought and salinity in sustainable agriculture.

Sub-Saharan Africa accounts for almost 70 % of people living with HIV (PLWH) worldwide, with the greatest numbers centred in South Africa where 98 % of infections are caused by subtype C (HIV-1C). However, HIV-1 subtype B (HIV-1B), prevalent in Europe and North America, has been the focus of most cure research and testing despite making up only 12 % of HIV-1 infections globally. Development of latency models for non-subtype B viruses is a necessary step to address this disproportionate focus. Furthermore, the impact of genetic variation between viral subtypes, specifically within the long terminal repeat (LTR) element of the viral transcriptional promoter on latency reversal, remains unclear. To address this scientific gap, we constructed a minimal genome retroviral vector expressing HIV-1C consensus transactivator of transcription protein (Tat) and green fluorescent protein (GFP) under the control of either HIV-1C consensus LTR (C731CC) or the transmitted/founder (T/F) LTRs derived from PLWH (CT/F731CC), produced corresponding LTR pseudotyped viruses using a vesicular stomatitis virus (VSV-G) pseudotyped Envelope vector and the pCMVΔR8.91 packaging vector containing HIV-1 accessory and rev genes. Viruses produced in this way were used to infect Jurkat E6 and primary CD4+ T cells in vitro. By enriching for latently infected cells, and treating them with different latency reversing agents, we developed an HIV-1C latency model that demonstrated that the HIV-1C consensus LTR has lower reactivation potential compared to its HIV-1B counterpart. Furthermore, HIV-1C T/F LTR pseudotyped proviral genetic variants exhibited a heterogenous reactivation response which was modulated by host cell (genetic) variation. Our data suggests that genetic variation both within and between HIV-1 subtypes influences latency reversal. Future studies should investigate the specific role of variation in host cellular environment on reactivation differences.

In the current study, we evaluated genetic variation and bottleneck analyses of Iraqi native cows in three locations of Babylon province. A total of 70 individuals of three cows' population were genotyped using ten the short tandem repeat markers (STR). The STR loci showed high variation of polymorphism. The average total number of alleles (TNA) and effective number of alleles (Ae) values were 5.30± 0.17 and 3.89± 0.11, respectively. The TNA at the marker level ranged from 3.00 (ETH3) to 8.00 (TGLA227), while the Ae ranged from 2.69 (ETH3) to 5.54 (TGLA227). The Shannon index (I) at the marker level ranged from 1.05 (ETH3) to 1.87 (TGLA227), with mean 1.48± 0.28. Also, the mean polymorphism information content (PIC) was 0.65±0.15, with a range of 0.54 (ETH3) to 0.81 (TGLA227). The average observed heterozygosity (Obs_Het) was 0.54 ± 0.18 and varied from 0.16 (ETH3) to 0.77 (TGLA53). The average expected heterozygosity (Exp_Het) was 0.75±0.25, with a range of 0.62 (ETH3) to 0.85 (TGLA227). The means HS unbiased gene diversity, and inbreeding coefficient (FIS) were 0.73±0.23, and 0.24±0.09, respectively. The mean Fis, Fit and Fst, and gene flow (Nm) were 0.296 ± 0.065, 0.314 ± 0.090, 0.032 ± 0.002, and 7.259 ± 2.113 respectively. The native cow's population is not at bottleneck, and normal L-shaped distribution of allele frequencies, that it has not experienced any recent decline in effective population size and has remained in equilibrium between mutation and drift. The Bayesian analysis showed that all animals were heterogeneous and formed three distinct clusters.

In the current study, we evaluated genetic variation and bottleneck analyses of Iraqi native cows in three locations of Babylon province. A total of 70 individuals of three cows' population were genotyped using ten the short tandem repeat markers (STR). The STR loci showed high variation of polymorphism. The average total number of alleles (TNA) and effective number of alleles (Ae) values were 5.30± 0.17 and 3.89± 0.11, respectively. The TNA at the marker level ranged from 3.00 (ETH3) to 8.00 (TGLA227), while the Ae ranged from 2.69 (ETH3) to 5.54 (TGLA227). The Shannon index (I) at the marker level ranged from 1.05 (ETH3) to 1.87 (TGLA227), with mean 1.48± 0.28. Also, the mean polymorphism information content (PIC) was 0.65±0.15, with a range of 0.54 (ETH3) to 0.81 (TGLA227). The average observed heterozygosity (Obs_Het) was 0.54 ± 0.18 and varied from 0.16 (ETH3) to 0.77 (TGLA53). The average expected heterozygosity (Exp_Het) was 0.75±0.25, with a range of 0.62 (ETH3) to 0.85 (TGLA227). The means HS unbiased gene diversity, and inbreeding coefficient (FIS) were 0.73±0.23, and 0.24±0.09, respectively. The mean Fis, Fit and Fst, and gene flow (Nm) were 0.296 ± 0.065, 0.314 ± 0.090, 0.032 ± 0.002, and 7.259 ± 2.113 respectively. The native cow's population is not at bottleneck, and normal L-shaped distribution of allele frequencies, that it has not experienced any recent decline in effective population size and has remained in equilibrium between mutation and drift. The Bayesian analysis showed that all animals were heterogeneous and formed three distinct clusters.

Diabetic nephropathy (DN), as the most serious minor vascular complication of diabetes, imposes a significant socioeconomic and medical cost around the world, and its prevention and treatment are a major challenge in the current medical community. Observational studies and randomized controlled trials have revealed protective and risk factors for some DN. However, the conclusions of these researches may be influenced by several types of confounding. Mendelian randomization is a new epidemiological method mainly used to infer the causal relationship between exposure and outcome. Many Mendelian randomization studies have found potential causal relationships between DN and some diseases and lifestyle habits, thus providing valuable data for future mechanistic studies as well as the development and implementation of clinical prevention strategies. As a result, the purpose of this review is to evaluate the published Mendelian randomization study of DN, using the bibliometric research method, analyze the current research status and hot spots, and further summarize the genetic evidence about the potential protection of DN and risk factors to provide new inspiration for the etiology of DN and as a reference for clinical intervention.

Grappling with climate change, and delving into variability among mung germplasm offers genetic stock. Therefore, harnessing RCB design, 16 mung genotypes were assessed in field & control environments through punctilious mixed models, and Duncan’s test (p ≤ 0.05) to assess stress indicators and yield attributes. This study divulges that 4 qualitative traits with a Shannon diversity index ranging from 0.41 to 0.74; 12 eigenvalues >1 contributed to 73% of variability. Likewise, the first 3 PCs accounted for variances: 19.25%, 8.39%, and 6.97%. From root architecture to yield attributes was captured in 3 PCs. Besides, elbow technique revealed that 4- clusters have a dissimilarity coefficient of 0.18; and disparate intra and inter-cluster distances, 440.6 (I) and 5959.402 (I-II), harbingering invaluable for hybridization. Path analysis revealed a positive association—post fertility traits & yield. Further, Duncan’s test elucidated that VC6370A, ideal in grain yield (2.432 tons/ha), subsequently CN95 (2.272 tons/ha). VC3960A-88 has the highest SPAD value (66.13), but Seedlings of VC6368 (46-40-3) is more apt to heat & drought-tolerant; in contrast, VC6370A has a deep root architecture, accentuating genes for water use efficiency & climate-resilient breeding. To add, MTSI disclose that VC6848, VC1973A(SC) were selected as stable & promising for improvement.

This study assessed the salt stress response of seventy soybean genotypes by exposing seedlings to sodium chloride (NaCl) concentrations of 0, 75, 100, and 125 mM. Salinity stress significantly reduced root length, shoot length, fresh and dry root/shoot weight, and root/shoot ratio. A total of 62 genotypes germinated at 125 mM, showing significant phenotypic variation in traits such as root length, shoot length, fresh shoot weight, and dry shoot weight. Pearson’s correlation analysis revealed a strong positive correlation between most morpho-physiological traits, suggesting their interdependence. Eight salinity tolerance indices i.e., Fresh Weight Stress Tolerance Index (FWSI), Dry Weight Stress Tolerance Index (DWSI), Root Length Salinity Index (RLSI), Shoot Length Salinity Index (SLSI), Salinity Tolerance Index (STI), Salinity Susceptibility Index (SSI), Tolerance Index (TI), and Percent Reduction (PR) were calculated to assess genotypes response. Na+ concentration and antioxidant activities significantly increased under salt stress compared to the control. The activities of antioxidant enzymes, as well as the levels of reactive oxygen species (ROS) such as H2O2 and O2−, were markedly higher under salt stress compared to the control. Hierarchical cluster analysis grouped genotypes into six clusters, with clusters V and VI comprising genotypes exhibiting higher salt tolerance based on high FWSI, DWSI, and STI values, and low PR, SSI, and TI values. Eight salinity tolerance indices, including Fresh Weight Stress Tolerance Index (FWSI), Dry Weight Stress Tolerance Index (DWSI), Root Length Salinity Index (RLSI), and Salinity Tolerance Index (STI), were used to evaluate the genotypes’ responses. The study revealed that the average FWSI value for all genotypes under treatments was 54.20 ± 12.93. The highest FWSI was recorded for the genotype Black (92.52), followed by NIBGE-224 (84.70) and NIBGE-183 (81.05). In contrast, Malakand-96 had the lowest FWSI (28.49), followed by SPS-10 (32.74) and SPS-08 (34.55). PGRA-91 had the highest STI (0.83), followed by SPS-9 (0.75) and NIBGE-115 (0.72), while NIBGE-335, SPS-24, and Malakand-96 had the lowest STI values. Positive correlations were observed between root length and shoot length (0.69**), shoot length and fresh shoot weight (0.63**), and other related traits. Overall, this study identified promising soybean genotypes with varying degrees of salt tolerance. These findings can be utilized in breeding programs to develop salt-tolerant soybean varieties for salinity-affected agricultural lands.

Abstract Thyroid dyshormonogenesis (TDH) is responsible for 15%–25% of congenital hypothyroidism (CH) cases. Pathogenetic variants of this common inherited endocrine disorders vary geographically. Unraveling the genetic underpinnings of TDH is essential for genetic counseling and precise therapeutic strategies. This study aims to identify genetic variants associated with TDH in Southern Taiwan using whole exome sequencing (WES). We included CH patients diagnosed through newborn screening at a tertiary medical center from 2011 to 2022. Permanent TDH was determined based on imaging evidence of bilateral thyroid structure and the requirement for continuous medication beyond 3 years of age. Genomic DNA extracted from blood was used for exome library construction, and pathogenic variants were detected using an in‐house algorithm. Of the 876 CH patients reviewed, 121 were classified as permanent, with 47 (40%) confirmed as TDH. WES was conducted for 45 patients, and causative variants were identified in 32 patients (71.1%), including DUOX2 (15 cases), TG (8 cases), TSHR (7 cases), TPO (5 cases), and DUOXA2 (1 case). Recurrent variants included DUOX2 c.3329G>A, TSHR c.1349G>A, TG c.1348delT, and TPO c.2268dupT. We identified four novel variants based on genotype, including TSHR c.1135C>T, TSHR c.1349G>C, TG c.2461delA, and TG c.2459T>A. This study underscores the efficacy of WES in providing definitive molecular diagnoses for TDH. Molecular diagnoses are instrumental in genetic counseling, formulating treatment, and developing management strategies. Future research integrating larger population cohorts is vital to further elucidate the genetic landscape of TDH.

Abstract Background As a result of the world population and climate change impact increases (especially in arid environments), there is a critical need for high-yield, drought-tolerant wheat. Synthetic hexaploid wheat derived lines (SHW-DL), were created artificially by crossing different durum wheat cultivars (AABB) with accessions of Aegilops tauschii (DD), a beneficial source of new genes for common bread wheat (Triticum aestivum L). Here, we studied the response of a panel of 91 SHW-DL for drought tolerance based on physiological, antioxidant enzyme activities, and drought tolerance indices. Results A wide range of variation and high values of heritability observed for grain yield, physiological and antioxidant traits indicating that the SHW-DL panel constitutes a valuable gene source for drought tolerance improvement of wheat. Despite decreases in grain yield (YLD), leaf area index (LAI), and relative water content (RWC) an increase in the content of malondialdehyde (MDA) was observed. Moreover, drought streass increased the antioxidant enzyme activities of ascorbate peroxidase (APX), catalase (CAT) and peroxidase (POD), and also photosynthetic pigments, proline (Pro), and MDA content. With higher values of grain yield, physiological and biochemical traits such as photosynthetic pigments, and RWC, and lower content of MDA, and peroxidase (H2O2) activity, SHW-DL performed better compared to common wheat lines under water stress conditions. Conclusions Different responses to water stress within the germplasm and between synthetic and common wheat suggest that selection for adaptive and suitable genotypes is possible for drought tolerance in synthetic wheat germplasm. Genotypes 54, 98, 102, 105, 122, 124, 143, 159, 196, and 198 were identified to be directly used in breeding programs or indirectly by crossing them with other wheat germplasm collections.

Abstract Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by social and communication difficulties, along with repetitive behaviors. While genetic factors play a significant role in ASD, the precise genetic landscape remains complex and not fully understood, particularly in non-syndromic cases. The study performed an in silico comparison of three genetic databases. ClinVar, SFARI Gene, and AutDB were utilized to identify relevant gene subset and genetic variations associated with non-syndromic ASD. Gene set enrichment analysis (GSEA) and protein–protein interaction (PPI) network analysis were conducted to elucidate the biological significance of the identified genes. The integrity of ASD-related gene subset and the distribution of their variations were statistically assessed. A subset of twenty overlapping genes potentially specific for non-syndromic ASD was identified. GSEA revealed enrichment of biological processes related to neuronal development and differentiation, synaptic function, and social skills, highlighting their importance in ASD pathogenesis. PPI network analysis demonstrated functional relationships among the identified genes. Analysis of genetic variations showed predominance of rare variants and database-specific distribution patterns. The results provide valuable insights into the genetic landscape of ASD and outline the genes and biological processes involved in the condition, while taking into account that the study relied exclusively on in silico analyses, which may be subject to biases inherent to database methodologies. Further research incorporating multi-omics data and experimental validation is warranted to enhance our understanding of non-syndromic ASD genetics and facilitate the development of targeted research, interventions and therapies.

Pinus oocarpa is a widely distributed species essential for resin production in Mexico, where demand surpasses supply. This study aimed to identify differences and variation levels of seedling emergence capacity and morphological traits in resin-producing high-yield P. oocarpa trees and estimate their genetic control. Seeds from 72 open-pollinated families were planted using a randomized complete block experimental design. Differences between families were determined and pooled using cluster analysis. We recorded wide differences in seed emergence capacity and morphological traits (cotyledon number and length, and hypocotyl length), allowing to establish three family groups. We also calculated the contribution of the variation sources to the total variance and genetic parameters involved. Our data evidenced high genetic control for all tested variables. We found a moderate and positive genetic correlation between cotyledon length, cotyledon number, and hypocotyl length. We also found a high negative genetic correlation between emergence capacity and hypocotyl length. At the phenotypic level, we found a high and significant correlation between cotyledon length and number. Grouping P. oocarpa into families should aid decision-making for sexual propagation since a high propagation capacity of the high-yield trees is essential for genetic improvement programs. Moreover, we demonstrate that the heritability of the emergence capacity and other morphological traits is high; these traits can be useful for the early selection of high-yield families.

Abstract Biogeographic barriers to gene flow are central to studies of plant phylogeography. There are many physical and geographic barriers in China, but few studies have used molecular ecological evidence to investigate the natural geographic isolation barrier of the Qinling Mountains-Huaihe River Line (QHL). Allium macrostemon is a precious Chinese perennial herb belonging to the Amaryllidaceae family. It is used as a food and medicine, with a variety of health and healing properties. Five SSR markers, three chloroplast DNA (cpDNA) markers (psbA-trnH, rps16 and trnL-F), one nuclear ribosomal DNA (nrDNA) marker (ITS), and simplified genome GBS sequencing were used to analyse the genetic diversity and structure of A. macrostemon. Combining SSR, cpDNA, nrDNA ITS data and GBS analysis results, we divided A. macrostemon populations into northern and southern groups, with the southern group further divided into southwestern and central-southeastern groups. Niche simulation results reveal that the distribution area of A. macrostemon will reach its maximum in the future. These data indicate that the regional separation of A. macrostemon has been maintained by the combined influence of a geographical barrier and Quaternary climate, and that the back-and-forth fluctuations of QHL and Quaternary climate have played an important role in this process. QHL acts as a north-south dividing line in phylogeography and population genetic structure, promoting physical geographic isolation. This study provides a theoretical basis for the conservation, development, and utilization of A. macrostemon resources. It further provides a reference for understanding the systematic geographical pattern of the large-scale spatial distribution of plants in China and enriches our understanding of Quaternary plant evolution in areas with complex terrain.

Abstract Background The globally transmitted avian malaria parasite Plasmodium relictum (lineage SGS1) has been found to infect hundreds of different bird species with differences in infection outcomes ranging from more or less latent to potentially mortal. However, to date basic knowledge about the links between genetic differentiation and variation in infection outcome within this single malaria parasite species is lacking. Methods In this study, two different isolates of SGS1, obtained in the wild from two different host species, were used to investigate differences in their development in the blood and virulence in the experimentally infected canaries. Simultaneously, 258 kb of the parasite genome was screened for genetic differences using parasite mRNA and compared between experimental groups. Results The two isolates showed differences in development and caused mortality as well as effects on the blood parameters of their hosts. Although previous studies using single genes have shown very limited within lineage genetic diversity in the European population of SGS1, 226 SNPs were found across 322 genes, which separated the two experimental groups with a total of 23 SNPs that were fixed in either of the experimental groups. Moreover, genetic variation was found within each experimental group, hinting that each avian malaria infection harbours standing genetic variation that might be selected during each individual infection episode. Conclusion These results highlight extensive genetic variation within the SGS1 population that is transferred into individual infections, thus adding to the complexity of the infection dynamics seen in these host–parasite interactions. Simultaneously, the results open up the possibility of understanding how genetic variation within the parasite populations is linked to the commonly observed differences in infection outcomes, both in experimental settings and in the wild. Graphical Abstract

Abstract Background Scopoletin and umbelliferone belong to coumarins, which are plant specialized metabolites with potent and wide biological activities, the accumulation of which is induced by various environmental stresses. Coumarins have been detected in various plant species, including medicinal plants and the model organism Arabidopsis thaliana. In recent years, key role of coumarins in maintaining iron (Fe) homeostasis in plants has been demonstrated, as well as their significant impact on the rhizosphere microbiome through exudates secreted into the soil environment. Several mechanisms underlying these processes require clarification. Previously, we demonstrated that Arabidopsis is an excellent model for studying genetic variation and molecular basis of coumarin accumulation in plants. Results Here, through targeted metabolic profiling and gene expression analysis, the gene-metabolite network of scopoletin and umbelliferone accumulation was examined in more detail in selected Arabidopsis accessions (Col-0, Est-1, Tsu-1) undergoing different culture conditions and characterized by variation in coumarin content. The highest accumulation of coumarins was detected in roots grown in vitro liquid culture. The expression of 10 phenylpropanoid genes (4CL1, 4CL2, 4CL3, CCoAOMT1, C3’H, HCT, F6’H1, F6’H2,CCR1 and CCR2) was assessed by qPCR in three genetic backgrounds, cultured in vitro and in soil, and in two types of tissues (leaves and roots). We not only detected the expected variability in gene expression and coumarin accumulation among Arabidopsis accessions, but also found interesting polymorphisms in the coding sequences of the selected genes through in silico analysis and resequencing. Conclusions To the best of our knowledge, this is the first study comparing accumulation of simple coumarins and expression of phenylpropanoid-related genes in Arabidopsis accessions grown in soil and in liquid cultures. The large variations we detected in the content of coumarins and gene expression are genetically determined, but also tissue and culture dependent. It is particularly important considering that growing plants in liquid media is a widely used technology that provides a large amount of root tissue suitable for metabolomics. Research on differential accumulation of coumarins and related gene expression will be useful in future studies aimed at better understanding the physiological role of coumarins in roots and the surrounding environments.

ABSTRACT: As the stress-inducible isoform of the heat-shock protein 90 (HSP90), the HSP90AA1 gene encodes HSP90α and plays an important role in heat stress (HS) response. Therefore, this study aimed to investigate the role of the HSP90AA1 gene in cellular responses during HS and to identify functional SNPs associated with thermotolerance in Holstein cattle. For the in vitro validation experiment of acute HS, cells from the Madin-Darby bovine kidney cell line were exposed to 42°C for 1 h, and various parameters were assessed, including cell apoptosis, cell autophagy, and the cellular functions of HSP90α by using its inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG). Furthermore, the polymorphisms identified in the HSP90AA1 gene and their functions related to HS were validated in vitro. Acute HS exposure induced cell apoptosis, cell autophagy, and upregulated expression of the HSP90AA1 gene. Inhibition of HSP90α by 17-AAG treatment had a significant effect on the expression of the HSP90α protein and increased cell apoptosis. However, autophagy decreased in comparison to the control treatment when cells were exposed to 42°C for 1 h. Five SNPs identified in the HSP90AA1 gene were significantly associated with rectal temperature and respiration score in Holstein cows, in which the rs109256957 SNP is located in the 3′ untranslated region (3′ UTR). Furthermore, we demonstrated that the 3′ UTR of HSP90AA1 is a direct target of bta-miR-1224 by cell transfection with exogenous microRNA (miRNA) mimic and inhibitor. The luciferase assays revealed that the SNP rs109256957 affects the regulation of bta-miR-1224 binding activity and alters the expression of the HSP90AA1 gene. Heat stress–induced HSP90AA1 expression maintains cell survival by inhibiting cell apoptosis and increasing cell autophagy. The rs109256957 located in the 3′ UTR region is a functional variation and it affects the HSP90AA1 expression by altering its binding activity with bta-miR-1224, thereby associating with the physiological parameters of Holstein cows.

Abstract Quinoa (Chenopodium quinoa, 2n = 4x = 36), a super pseudocereal crop, has been introduced into China nearly 60 years. Many excellent varieties have been developed through massive selection; however, few are developed through mutagenesis breeding. In this study, the ‘Longli-4’ variety, locally cultivated in Gansu province, Northwest China, was selected for experimentation. The grains of ‘Longli-4’ were treated with ethyl methanesulfonate (EMS) at a concentration of 0.8% for 8 h. Nine plants from independent M2 families were randomly selected to investigate the mutagenesis effect of EMS on the quinoa genome. The results indicated that the single nucleotide polymorphisms (SNPs) induced by EMS were unevenly distributed across all 18 chromosomes, with an average mutation frequency of 91.2 SNPs/Mb, ranging from 4.5 to 203.5 SNPs/Mb. A significant positive correlation between the number of SNPs and chromosome length was identified through linear model analysis. Transitions from G/C to A/T were the most predominated in all variant categories, accounting for 34.4–67.2% of the mutations, and SNPs were significantly enriched in intergenic regions, representing 69.2–75.1% of the total mutations. This study provides empirical support for the application of low concentration EMS treatment in quinoa breeding.

The basis for criteria of the taxonomic classification of DNA and RNA viruses based on data of the genomic sequencing are viewed in this review. The genomic sequences of viruses, which have genome represented by double-stranded DNA (orthopoxviruses as example), positive-sense single-stranded RNA (alphaviruses and flaviviruses as example), non-segmented negative-sense single-stranded RNA (filoviruses as example), segmented negative-sense single-stranded RNA (arenaviruses and phleboviruses as example) are analyzed. The levels of genetic variability that determine the assignment of compared viruses to taxa of various orders are established for each group of viruses.

Abstract Background Enhancing crops’ drought resilience is necessary to maintain productivity levels. Plants interact synergistically with microorganisms like Beauveria bassiana to improve drought tolerance. Therefore, the current study investigates the effects of biopriming with B. bassiana on drought tolerance in Malva parviflora plants grown under regular irrigation (90% water holding capacity (WHC)), mild (60% WHC), and severe drought stress (30% WHC). Results The results showed that drought stress reduced the growth and physiological attributes of M. parviflora. However, those bioprimed with B. bassiana showed higher drought tolerance and enhanced growth, physiological, and biochemical parameters: drought stress enriched malondialdehyde and H2O2 contents. Conversely, exposure to B. bassiana reduced stress markers and significantly increased proline and ascorbic acid content under severe drought stress; it enhanced gibberellic acid and reduced ethylene. Bioprimed M. parviflora, under drought conditions, improved antioxidant enzymatic activity and the plant’s nutritional status. Besides, ten Inter-Simple Sequence Repeat primers detected a 25% genetic variation between treatments. Genomic DNA template stability (GTS) decreased slightly and was more noticeable in response to drought stress; however, for drought-stressed plants, biopriming with B. bassiana retained the GTS. Conclusion Under drought conditions, biopriming with B. bassiana enhanced Malva’s growth and nutritional value. This could attenuate photosynthetic alterations, up-regulate secondary metabolites, activate the antioxidant system, and maintain genome integrity.

Von Hippel-Lindau disease (VHL disease) is a hereditary tumor syndrome caused by VHL mutations. VHL disease-related tumors are often multiple and mostly treated by surgery. However, they often relapse after surgery. The VHL gene functions as a tumor suppressor through both hypoxia-inducible factor (HIF) dependent and HIF-independent pathway. Research on the genetic mechanisms of VHL disease has laid the foundation for the treatment of the disease. In recent years, the targeted drugs based on the genetic mechanism of VHL disease have provided a new approach for the treatment of the disease. Small molecule targeted drugs such as belzutifan and tyrosine kinase inhibitors, which act on the hypoxia signaling pathway, have shown excellent prospects for the treatment of VHL disease.The study aimed to summarize the genetic mechanisms and advances in related treatment of VHL disease. More in-depth clinical research on targeted drugs for VHL disease will provide more treatment options for the patients.

Abstract Whole genome and exome sequencing are reporting on hundreds of thousands of missense mutations. Taking a pan-disease approach, we explored how mutations in intrinsically disordered regions (IDRs) break or generate protein interactions mediated by short linear motifs. We created a peptide-phage display library tiling ~57,000 peptides from the IDRs of the human proteome overlapping 12,301 single nucleotide variants associated with diverse phenotypes including cancer, metabolic diseases and neurological diseases. By screening 80 human proteins, we identified 366 mutation-modulated interactions, with half of the mutations diminishing binding, and half enhancing binding or creating novel interaction interfaces. The effects of the mutations were confirmed by affinity measurements. In cellular assays, the effects of motif-disruptive mutations were validated, including loss of a nuclear localisation signal in the cell division control protein CDC45 by a mutation associated with Meier-Gorlin syndrome. The study provides insights into how disease-associated mutations may perturb and rewire the motif-based interactome.

Abstract Background Individuals born with cleft lip and/or palate who receive corrective surgery regularly have abnormal growth in the midface region such that they exhibit premaxillary hypoplasia. However, there are also genetic contributions to craniofacial morphology in the midface region, so although these individuals appear to have Class III skeletal discrepancy, their molar relationship may be Class I. Past genome-wide association studies (GWASs) on skeletal Class II and III malocclusion suggested that multiple genetic markers contribute to these phenotypes via a multifactorial inheritance model, but research has yet to examine the genetic markers associated with dental Class I malocclusion. Thus, our goal was to conduct a family based GWAS to identify genes across the genome that are associated with Class I malocclusion, as defined by molar relations, in humans with and without clefts. Methods Our cohort consisted of 739 individuals from 47 Filipino families originally recruited in 2006 to investigate the genetic basis of orofacial clefts. All individuals supplied blood samples for DNA extraction and genotyping, and a 5,766 single nucleotide polymorphism (SNP) custom panel was used for the analyses. We performed a transmission disequilibrium test for participants with and without clefts to identify genetic contributors potentially involved with Class I malocclusion. Results In the total cohort, 13 SNPs had associations that reached the genomic control threshold (p

Abstract Background Respiratory Syncytial Virus (RSV) disease in young children ranges from mild cold symptoms to severe symptoms that require hospitalization and sometimes result in death. Studies have shown a statistical association between RSV subtype or phylogenic lineage and RSV disease severity, although these results have been inconsistent. Associations between variation within RSV gene coding regions or residues and RSV disease severity has been largely unexplored. Methods Nasal swabs from children (

The conservation of endemic plant species has come into the global spotlight, not only because of their contribution to biodiversity but also their vulnerability and high extinction risk due to environmental and anthropogenic threats. Based on these developments, it is now essential to monitor and protect these species by applying integrated conservation strategies, especially in view of climate change, which is one of the most severe threats to plants. Genetic and genomic tools provide new potential in assessing and quantifying genetic diversity and thus can be utilized to devise conservation strategies and contribute to biodiversity conservation efforts. Greece comprises a plant biodiversity hotspot in the Mediterranean Basin with a wide variety of rare, threatened, and endemic plant taxa. In this review, we examine several cases where a broad spectrum of genetic tools has been utilized so far in the diversity assessment and conservation management of Greek Endemic Plants (GEPs). Following an extensive database search, we have identified and included in our final data collection 19 studies concerning 32 GEPs for which molecular markers have been used for the determination of population genetic structure and diversity assessment, while at the same time, the research outcomes have been taken into consideration for conservation management. The limited application of genetic and genomic tools in GEP management is demonstrated, while the significance of implementing a comprehensive conservation strategy that will integrate genetic analyses and the data derived therein is also highlighted.

Targeted therapy is crucial for advanced colorectal cancer (CRC) positive for genetic drivers. With advances in deep sequencing technology and new targeted drugs, existing standard molecular pathological detection systems and therapeutic strategies can no longer meet the requirements for careful management of patients with advanced CRC. Thus, rare genetic variations require diagnosis and targeted therapy in clinical practice. Rare gene mutations, amplifications, and rearrangements are usually associated with poor prognosis and poor response to conventional therapy. This review summarizes the clinical diagnosis and treatment of rare genetic variations, in genes including erb-b2 receptor tyrosine kinase 2 (ERBB2), B-Raf proto-oncogene, serine/threonine kinase (BRAF), ALK receptor tyrosine kinase/ROS proto-oncogene 1, receptor tyrosine kinase (ALK/ROS1), neurotrophic receptor tyrosine kinases (NTRKs), ret proto-oncogene (RET), fibroblast growth factor receptor 2 (FGFR2), and epidermal growth factor receptor (EGFR), to enhance understanding and identify more accurate personalized treatments for patients with rare genetic variations.