Genetic Groups Research Articles

Population connectivity and size reductions in the Anthropocene: the consequence of landscapes and historical bottlenecks in white forsythia fragmented habitats

BackgroundWhite forsythia (Abeliophyllum distichum) is an endangered Korean Peninsula endemic that has been subjected to recent population genomics studies using SNPs via RAD sequencing. Here, we primarily employed the often underutilized haplotype information from RAD loci to further describe the species’ previously uninvestigated haplotype-based genomic variation and structure, and genetic-geographic characteristics and gene flow patterns among its five earlier identified genetic groups. We also inferred the time of past events that may have impacted the effective population size of these groups, as well as the species’ potential future distribution amidst the warming climate and anthropogenic threats.ResultsOur findings emphasized the recognition of the species’ regional patterns of genetic structure, and the role of topography and its associated gene flow patterns as some of the possible factors that may have influenced the species’ present-day fragmented population distribution. The inferred bottleneck events during the Anthropocene, some of which aligned with the time of historical catastrophic events on the Peninsula (e.g., the Korean War), were revealed to have contributed to the generally low effective population size of its five lineages, particularly those with marginal distributional range. Future distribution under both optimistic and pessimistic climatic scenarios suggests unlikely suitable habitats for these populations to expand from their current range limits, at least in the next 80 years.ConclusionsThe small effective population size and landscape-driven limited gene flow among white forsythia populations will remain a big challenge for the conservation management of the species’ already fragmented population distribution. To help mitigate these impacts, the merging of various research approaches and the use of genomic data to their full potential is recommended to provide the optimized knowledge-based tools for the conservation of this endangered species, and other similar plants under pressure.

Genetic characterisation of Annona crassiflora as basis for conservation and breeding

Abstract Annona crassiflora is a fruit-bearing tree species native to the Cerrado that has ecological and economic potential, mainly due to the production of attractive and useful fruits for a number of species, including humans. To provide a basis for its conservation and breeding, the objective was to assess the diversity and genetic structure of natural populations of the species using inter-simple sequence repeat (ISSR) molecular markers. Eight populations were analysed in the state of Minas Gerais, Brazil, with 24 individuals randomly sampled in each population, reaching a total of 192 trees. Ten ISSR primers were used, resulting in high genetic diversity for the combined data (H* = 0.35 and I* = 0.52). However, a wide range of representative values was observed in the individual assessment of populations, with JAN, GM and MC standing out for their low genetic diversity, resulting in H* of 0.19, 0.23 and 0.24 and I* of 0.28, 0.34 and 0.35, respectively. An analysis of molecular variance showed greater variation within populations, indicating gene flow (Nm), but genetic differentiation between populations was moderate. Bayesian analysis, although resulting in four genetic groups, revealed the presence of a majority group for the GM and JAN populations. We propose measures to maintain these populations, such as raising awareness of local extractivism and planting genetically divergent seedlings. Furthermore, we recommend including of all populations in conservation and breeding programmes, aiming to cover the maximum genetic variation for the species.

Effectiveness of vigabatrin for infantile epileptic spasm syndrome categorized by etiologies

PurposeWe aimed to assess the effectiveness of vigabatrin (VGB) in patients diagnosed with infantile epileptic spasm syndrome (IESS) and categorize these patients based on their etiologies. MethodsThis retrospective study included patients diagnosed with IESS who exhibited epileptic spasms before the age of 2 years between January 1, 2015, and October 31, 2023 at Saitama Children's Medical Center. Patients with tuberous sclerosis as the identified etiology were excluded. The effectiveness of VGB was assessed based on the resolution of ES for three months with the absence of hypsarrhythmia on interictal electroencephalogram. ResultsThis study analyzed 41 patients (26 boys). The etiologies included genetic, congenital structural, acquired structural, and unknown in 12, 11, 10, and 8 patients, respectively. Patient characteristics did not significantly differ among the four groups. The overall effectiveness of VGB for IESS was 39.0 % (16/41). Categorized based on etiology, VGB was effective in 41.7 % (5/12), 9.1 % (1/11), 50 % (5/10), and 75 % (6/8) in the genetic, congenital structural, acquired structural, and unknown groups, respectively. Statistical analysis revealed a significant difference in effectiveness among the four groups (p = 0.03). Categorized based on diseases, VGB was effective in 28.6 % (2/7) and 50 % (4/8) in trisomy 21 and perinatal brain injury, respectively. ConclusionThe effectiveness of VGB in patients with IESS varied with etiology. Further investigations into the effectiveness of VGB in etiological subtypes of IESS could facilitate the development of tailored treatment algorithms for each etiology, representing valuable guidelines for future medical practice.

Association of Polygenic Risk Score With Lifetime Risk of Developing Multiple Sclerosis in a Population-Based Birth-Year Cohort.

More than 200 genetic variants have been associated with multiple sclerosis (MS) susceptibility. However, it is unclear to what extent genetic factors influence lifetime risk of MS. Using a population-based birth-year cohort, we investigate the effect of genetics on lifetime risk of MS. In the Project Y study, we tracked down almost all persons with MS (pwMS) from birth year 1966 in the Netherlands. As control participants, we included non-MS participants from the Project Y cohort (born 1965-1967 in the Netherlands) and non-MS participants from the Amsterdam Dementia Cohort born between 1963 and 1969. Genetic variants associated with MS were determined in pwMS and control participants using genotyping or imputation methods. Polygenic risk scores (PRSs) based on variants and weights from the largest genetic study in MS were calculated for each participant and assigned into deciles based on the PRS distribution in the control participants. We examined the lifetime risk for each decile and the association between PRS and MS disease variables, including age at onset and time to secondary progression. MS-PRS was calculated for 285 pwMS (mean age 53.0 ± 0.9 years, 72.3% female) and 267 control participants (mean age 51.8 ± 3.2 years, 58.1% female). Based on the lifetime risk estimation, we observed that 1:2,739 of the women with the lowest 30% genetic risk developed MS, whereas 1:92 of the women with the top 10% highest risk developed MS. For men, only 1:7,900 developed MS in the lowest 30% genetic risk group, compared with 1:293 men with the top 10% genetic risk. The PRS was not significantly associated with age at onset and time to secondary progression in both sexes. Our results show that the lifetime risk of MS is strongly influenced by genetic factors. Our findings have the potential to support diagnostic certainty in individuals with suspected MS: a high PRS could strengthen a diagnosis, but especially a PRS from the lowest tail of the PRS distribution should be considered a red flag and could prevent misdiagnosing conditions that mimic MS.

Whole-Genome Resequencing Reveals Significant Genetic Differentiation Between Exserohilum turcicum Populations from Maize and Sorghum and Candidate Effector Genes Related to Host Specificity.

Exserohilum turcicum is a devastating fungal pathogen that infects both maize and sorghum, leading to severe leaf diseases of the two crops. According to host specificity, pathogenic isolates of E. turcicum are divided into two formae speciales, namely E. turcicum f. sp. zeae and E. turcicum f. sp. sorghi. To date, the molecular mechanism underlying the host specificity of E. turcicum is marginally known. In this study, the whole genomes of 60 E. turcicum isolates collected from both maize and sorghum were resequenced, which enabled identification of 233,022 single-nucleotide polymorphisms (SNPs) in total. Phylogenetic analysis indicated that all isolates are clustered into four genetic groups that have a close relationship with host source. This observation is validated by the result of principal component analysis. Analysis of population structure revealed that there is obvious genetic differentiation between two populations from maize and sorghum. Further analysis showed that 5,431 SNPs, including 612 nonsynonymous SNPs, are completely co-segregated with the host source. These nonsynonymous SNPs are located in 539 genes, among which 18 genes are predicted to encode secretory proteins, including six putative effector genes named SIX13-like, Ecp6, GH12, GH28-1, GH28-2, and CHP1. Sequence polymorphism analysis revealed various numbers of SNPs in the coding regions of these genes. These findings provide new insights into the molecular basis of host specificity in E. turcicum.

Correlation between the etiology of severe hearing loss and endolymphatic hydrops.

This study aimed to investigate correlation between the presence of endolymphatic hydrops(EH) and factors such as causes of hearing loss, patient age, duration of deafness, and results of vestibular function tests. We retrospectively reviewed medical charts of 128 ears of cochlear implantees who were not considered relevant to Meniere's disease. When comparing group with genetic variants of GJB2, SLC26A4, LMX1A and other genetic mutation group, the proportion of vestibular EH and cochlear EH found in group with genetic variants of GJB2, SLC26A4, LMX1A was significantly higher than group with other genetic etiology (p < 0.01) or the group with all the other causes of hearing loss (p < 0.01). The rate of vestibular and cochlear EH detection was higher in younger patients (41.5% and 35.4%) than in older patients (25.4% and 20.6%). A higher ratio of vestibular and cochlear EH was observed in patients with a longer duration of deafness (37.5% and 31.3%) than those with a shorter duration of deafness (29.7% and 25.0%). The group with vestibular EH showed a higher incidence of abnormal findings in the caloric test (42.9%) than the group without vestibular EH (28.2%). Patients with genetic variants of GJB2, SLC26A4, LMX1A, younger patients, those with longer deaf durations showed a higher prevalence of vestibular and cochlear EH, implying EH appears to be formed as a developmental disorder in association with a certain set of genetic variants, rather than a phenotypic marker as a result of severe to profound hearing loss.

Chromosome-scale genome assembly of acerola (Malpighia emarginata DC.).

Acerola (Malpighia emarginata DC.) is a tropical evergreen shrub that produces vitamin C-rich fruits. Increasing fruit nutrition is one of the main targets of acerola breeding programs. Genomic tools have been shown to accelerate plant breeding even in fruiting tree species, which generally have a long life cycle; however, the availability of genomic resources in acerola, so far, has been limited. In this study, as a first step toward developing an efficient breeding technology for acerola, we established a chromosome-scale genome assembly of acerola using high-fidelity long-read sequencing and genetic mapping. The resultant assembly comprises 10 chromosome-scale sequences that span a physical distance of 1,032.5Mb and contain 35,892 predicted genes. Phylogenetic analysis of genome-wide SNPs in 60 acerola breeding materials revealed three distinct genetic groups. Overall, the genomic resource of acerola developed in this study, including its genome and gene sequences, genetic map, and phylogenetic relationship among breeding materials, will not only be useful for acerola breeding but will also facilitate genomic and genetic studies on acerola and related species.

Genetic diversity and population structure of superior shea trees (Vitellaria paradoxa subsp. paradoxa) using SNP markers for the establishment of a core collection in Côte d'Ivoire.

The shea tree is a well-known carbon sink in Africa that requires a sustainable conservation of its gene pool. However, the genetic structure of its population is not well studied, especially in Côte d'Ivoire. In this study, 333 superior shea tree genotypes conserved in situ in Côte d'Ivoire were collected and genotyped with the aim of investigating its genetic diversity and population structure to facilitate suitable conservation and support future breeding efforts to adapt to climate change effects. A total of 7,559 filtered high-quality single nucleotide polymorphisms (SNPs) were identified using the genotyping by sequencing technology. The gene diversity (HE) ranged between 0.1 to 0.5 with an average of 0.26, while the polymorphism information content (PIC) value ranged between 0.1 to 0.5 with an average of 0.24, indicating a moderate genetic diversity among the studied genotypes. The population structure model classified the 333 genotypes into three genetic groups (GP1, GP2, and GP3). GP1 contained shea trees that mainly originated from the Poro, Tchologo, and Hambol districts, while GP2 and GP3 contained shea trees collected from the Bagoué district. Analysis of molecular variance (AMOVA) identified 55% variance within populations and 45% variance within individuals, indicating a very low genetic differentiation (or very high gene exchange) between these three groups (FST = 0.004, gene flow Nm = 59.02). Morphologically, GP1 displayed spreading tree growth habit, oval nut shape, higher mean nut weight (10.62g), wide leaf (limb width = 4.63cm), and small trunk size (trunk circumference = 133.4cm). Meanwhile, GP2 and GP3 showed similar morphological characteristics: erect and spreading tree growth habit, ovoid nut shape, lower mean nut weight (GP2: 8.89g; GP3: 8.36g), thin leaf (limb width = 4.45cm), and large trunk size ( GP2: 160.5cm, GP3: 149.1cm). A core set of 100 superior shea trees, representing 30% of the original population size and including individuals from all four study districts, was proposed using the "maximum length sub-tree function" in DARwin v. 6.0.21. These findings provide new knowledge of the genetic diversity and population structure of Ivorian shea tree genetic resources for the design of effective collection and conservation strategies for the efficient use of inbreeding.

Circulating ketone bodies, genetic susceptibility, with left atrial structure, function and atrial fibrillation: A prospective study from the UK Biobank

BackgroundKetone bodies (KBs) are an important cardiac metabolic energy source. Metabolic remodeling has recently been found to play an important role in the pathological process of atrial fibrillation (AF). ObjectiveThe purpose of this study was to evaluate the associations of circulating KB levels with incident AF risk in the general population. MethodsWe studied 237,163 participants (mean age 56.5 ± 8.1 years; 55% women) from the UK Biobank who were free of AF at baseline and had data on circulating β-hydroxybutyrate (β-OHB), acetoacetate, and acetone. The associations of KB with new-onset AF were evaluated using Cox regression in the general population and across the 3 genetic risk groups: low, moderate, and high polygenic risk score of AF. ResultsDuring a median follow-up of 14.8 years, 16,638 participants (7.0%) developed AF. There was a U-shaped association of total KB and β-OHB with incident AF, with nadirs at 60.6 and 40.8 μmol/L, respectively (Pnonlinear < .05), whereas there was a positive association of acetoacetate and acetone with AF (Poverall < .001; Pnonlinear > .05). Consistently, there was a U-shaped association of total KB and β-OHB with left atrial (LA) volume parameters, including LA maximum volume, LA minimum volume, and their body surface area–indexed counterparts, and there was an inverted U-shaped association of total KB with LA ejection fraction (Pnonlinear < .05 for all). The association of KB with AF was stronger in individuals with low genetic risk (Pinteraction < .05), while the highest AF risk was in those with high genetic risk with high KB levels. Significant mediation effects of inflammatory markers on the associations between KB and AF were identified. ConclusionThere was a U-shaped association of circulating total KB and β-OHB with incident AF as well as a positive association of acetoacetate and acetone levels with AF risk in the general population.

Assessment of Genetic Parameters and Diversity Organization of Ginger Accessions Cultivated in Burkina Faso as Revealed by Microsatellite Markers

Rhizomes of Ginger (Zingiber officinale Rosc.) are widely used as a spice across the world. It has originated from South-east Asia and introduced to many parts of the world, and has been cultivated as a spice and for medicinal purpose. Ginger is a high value crop in Burkina Faso. The genetic diversity organization in ginger species is not well-known in Burkina Faso. Genetic resources are imperative for varietal selection. The importance of genetic resources depends on the levels of their diversity. The present investigation aims to assess the diversity of ginger accessions collected from Burkina Faso. Forty-seven ginger accessions collected from three provinces, Comoé (03), Léraba (14), Kénédougou (30), located in the southwestern zone of Burkina Faso were genotyped for their molecular traits using microsatellite markers. A total of 24 alleles were revealed by electrophoresis. All the simple-sequence repeats (SSR) set primers used revealed high polymorphic rate (100%) with the expected heterozygosity (0.499), showing their ability in assessment of the diversity levels and genetic organization of ginger accessions due to their codominance. The dendrogram obtained by the Neighbor-Joining method revealed three main genetic groups. The genetic differentiation index value (0.313) showed that the accessions of the three provinces were different, with an interesting diversity observed from kénédougou ginger accessions. Information from this study could be used in the development of effective management strategies for the conservation and effective use of the genetic resources within ginger accessions grown in Burkina Faso.

Local adaptation of Dromiciops marsupials (Microbiotheriidae) from southern South America: Implications for species management facing climate change.

The two species of the microbiotheriid marsupial genus Dromiciops (Dromiciops bozinovici: "Panchos's monito del monte" and Dromiciops gliroides: "monito del monte") exhibit a marked latitudinal genetic differentiation. Nevertheless, it is unclear whether this differentiation results from neutral processes or can be explained, to some extent, by local adaptation to different environmental conditions. Here, we used an SNP panel gathered by Rad-seq and searched for footprints of local adaptation (putative loci under selection) by exploring genetic associations with environmental variables in the two species of Dromiciops in Chilean and Argentinean populations. We applied three methods for detecting outlier SNPs and two genotype-environment associations approaches to quantify associations between allelic frequencies and environmental variables. Both species display strong genetic structure. D. bozinovici exhibited three distinct genetic groups, marking the first report of such structuring in this species using SNPs. In contrast, D. gliroides displayed four genetic clusters, consistent with previous studies. Both species exhibited an association of their genetic structure with environmental variables. D. bozinovici exhibited significant associations of allelic frequencies with elevation, precipitation during the warmest periods, and seasonality in the thermal regime. For D. gliroides, genetic variation appeared to be associated with more variables than D. bozinovici, including precipitation and temperature-related variables, isothermality, and elevation. All the outlier SNPs were mapped to the D. gliroides reference genome to explore if they fell within functionally known genes. These results represent a necessary first step toward identifying the genome regions that harbor genes associated with climate adaptations in Dromiciops. Notably, we identified genes involved in various functions, including carbohydrate synthesis (ALG8), muscle and neuronal regulation (MEF2D), and stress responses (PTGES3). Ultimately, this study contributes valuable insights that can inform targeted conservation strategies aimed at preserving the genetic diversity of Dromiciops in the face of environmental challenges.

Combined genomic evaluation of Merino and Dohne Merino Australian sheep populations.

The Dohne Merino sheep was introduced to Australia from South Africa in the 1990s. It was primarily used in crosses with the Merino breed sheep to improve on attributes such as reproduction and carcass composition. Since then, this breed has continued to expand in Australia but the number of genotyped and phenotyped purebred individuals remains low, calling into question the accuracy of genomic selection. The Australian Merino, on the other hand, has a substantial reference population in a separate genomic evaluation (MERINOSELECT). Combining these resources could fast track the impact of genomic selection on the smaller breed, but the efficacy of this needs to be investigated. This study was based on a dataset of 53,663 genotypes and more than 2 million phenotypes. Its main objectives were (1) to characterize the genetic structure of Merino and Dohne Merino breeds, (2) to investigate the utility of combining their evaluations in terms of quality of predictions, and (3) to compare several methods of genetic grouping. We used the 'LR-method' (Linear Regression) for these assessments. We found very low Fst values (below 0.048) between the different Merino lines and Dohne breed considered in our study, indicating very low genetic differentiation. Principal component analysis revealed three distinct groups, identified as purebred Merino, purebred Dohne, and crossbred animals. Considering the whole population in the reference led to the best quality of predictions and the largest increase in accuracy (from 'LR-method') from pedigree to genomic-based evaluations: 0.18, 0.14 and 0.16 for yearling fibre diameter (YFD), yearling greasy fleece weight (YGFW) and yearling liveweight (YWT), respectively. Combined genomic evaluations showed higher accuracies than the evaluation based on the Dohne reference only (accuracies increased by 0.16, 0.06 and 0.07 for YFD, YGFW, and YWT, respectively). For the combined genomic evaluations, metafounder models were more accurate than Unknown Parent Groups models (accuracies increased by 0.04, 0.04 and 0.06 for YFD, YGFW and YWT, respectively). We found promising results for the future transition of the Dohne breed from pedigree to genomic selection. A combined genomic evaluation, with the MERINOSELECT evaluation in addition to using metafounders, is expected to enhance the quality of genomic predictions for the Dohne Merino breed.

Demographic history of Platypus quercivorus (Coleoptera: Curculionidae), a beetle causing mass mortality of oak trees, in eastern Japan

Abstract In recent years, Japanese oak wilt causing mass mortality of oak trees has exhibited a significant geographical expansion. Understanding the formation history of current local populations of Platypus quercivorus Murayama, a vector of Japanese oak wilt, is important foundational knowledge for effectively preventing forest damage. In this study, we used genome-wide single nucleotide polymorphism data to infer the population genetic structure and historical demography of P. quercivorus populations in eastern Japan, where Japanese oak wilt is rapidly expanding. We found at least 3 distinct genetic groups, each of which caused Japanese oak wilt in different areas. The supported scenario suggests that 1 of 2 genetic groups in the northeast first diverged from the ancestral population, then the other group diverged from the southwestern population, followed by gene flow between the 2 groups. Recent admixtures of the 2 northeastern groups were identified at certain sites. The geographic genetic structure of the populations suggested that each genetic group experienced recent range expansion. Although genetically independent populations had caused oak tree mass mortality in their original distribution range, our results support the hypothesis that the recent geographic expansion of Japanese oak wilt outbreaks is attributed to the range expansion of these P. quercivorus groups.

The involvement of proinflammatory cytokines in the pathogenesis of audiogenic epilepsy

Epilepsy is a heterogeneous disease, which determines the relevance of investigating the mechanisms of pathogenesis of its various types, including reflex epilepsy. Pharmacotherapy is common for the treatment of patients with epilepsy, however, despite the significant recent achievements, 20-30% of patients remain resistant to the ongoing treatment. The urgency of creating new antiepileptic drugs, in particular, immune ones is due not only to a significant proportion of pharmacoresistant cases, but also to the struggle for the quality of life of patients. The neuroinflammation system in animals with different genetically determined audiogenic epilepsy proneness was investigated. These genetic groups were Krushinsky–Molodkina rats (tonic seizures of maximum intensity in response to the action of sound) and “0” strain (control group, non-convulsive phenotype). The main proinflammatory cytokines levels in the dorsal striatum and brain stem in rats of these genetic groups were measured by multiplex immunofluorescence assay. Background levels of IL-1â, IL-6 and TNFá in the dorsal striatum of KM rats were significantly lower than in the control “0” strain rats, whereas in the brain stem in the “background” levels of these metabolites did not differ. Four hours after the sound exposure, the TNFá level in the dorsal striatum of KM rats was significantly lower than in “0” rats. In KM rats, after the sound exposure and subsequent tonic seizures, the levels of IL-1â and IL-6 in the dorsal striatum were significantly higher than in the background. The IL-2 content was not detected in the background in KM rats, whereas after audiogenic seizures its level was 14.01 pg/ml. In the brain stem of KM rats, the levels of IL-1â and TNFá after audiogenic seizures were significantly lower than in the background. In rats of the “0” strain, cytokine levels in the dorsal striatum after the sound exposure did not differ from those in the background, while IL-1ß levels in their brain stem were significantly lower than the background state. Particular modulating role of the studied proinflammatory cytokines in the pathogenesis of audiogenic epilepsy is assumed, as well as certain possibility of anti-inflammatory and immune drugs application in anticonvulsant and antiepileptic therapy.

Effects of Aqueous Extracts of Neem Leaf and Ginger Rhizome on Growth Performance and Haematological Parameters of Pure and Crossbred Chickens

Neem leaf and ginger rhizome contain numerous chemical components that are biologically active and are widely utilized in medications to treat various illnesses. The purpose of the current study was to assess the effect of aqueous neem leaf and ginger rhizome extracts on the growth performance and hematological parameters in the three breeds of chicken. A total of 360 one-day-old chicks from 3 genetic groups consisting of 120 Noiler chicks, 120 Heavy Ecotype chicks, and 120 main cross chicks were considered for this study. Each breed of chickens was randomly distributed into four groups, with three replications per group. Each replication consisted of eight females and two males, raised in a deep litter system. A 3×4 factorial arrangement was employed, involving four levels of plant extracts: a control group receiving the basal diet without any extract, a group receiving 200 ml of neem extract (NE200), a group receiving 200 ml of ginger extract (GE200), and a group receiving 100 ml of neem + 100 ml of ginger extract (NE100+GE100). The chickens were evaluated for growth parameters such as initial weight (IW), final weight (FW), average daily gain (ADG), average feed intake (AFI), feed conversion ratio (FCR) as well as some haematological parameters such as haemoglobin (Hb), packed cell volume (PCV), white blood cell (WBC), red blood cell (RBC), platelet (P), mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), and mean corpuscular haemoglobin concentration (MCHC). Noiler chickens receiving NE100+GE100 and GE200 showed the highest final body weight and daily weight gain. The results of the haematological indices revealed that the interaction effect of genotype and plant extracts on all the treatment groups were significantly different for haemoglobin (Hb), packed cell volume (PCV), white blood cell (WBC), and platelet (P). Some haematological indices such as Hb, PCV, WBC, and platelet were better for chickens receiving GE200 and NE100+GE100 compared to NE200 and control groups. In conclusion, the interaction of GE200 and NE100+GE100 with Noiler and main cross chickens was beneficial, with no adverse effects on the physiological traits and health status of the chickens 16 weeks of age. Keywords: Haematology, Heavy ecotype, Heterosis, Noiler, Performance, Plant extracts

Genetic characteristics of influenza A and B viruses circulating in Russia in 2019-2023.

Relevance. Influenza viruses have a high potential for genetic change. These viruses are monitored annually around the world, including Russia, to determine the dominant genetic groups and select the strains to be included in influenza vaccines. Aims of the study include: analysis of the circulation of influenza viruses in Russia in 2019-2023, phylogenetic and molecular analysis of hemagglutinin (HA) sequences of influenza virus strains, detection of drug resistance mutations to neuraminidase (NA) inhibitors and M2-protein (M2) ion channel inhibitors. Materials and methods. Biological samples containing RNA of influenza viruses were studied: 417 A(H1N1)pdm09, 147 A(H3N2) and 167 B(Victoria). Sequencing of the PCR fragments was performed on the 3500xL Genetic Analyzer (Applied Biosytems). Data processing and analysis were carried out using DNASTAR, Nextclade, FluSurver and BioNumerics v.6.6 software. Results. Influenza A(H1N1)pdm09, A(H3N2), B(Victoria) viruses circulating in 2019-2023 were investigated. The highest variability of HA was observed in A(H3N2) viruses. 3% of A(H1N1)pdm09 viruses had the D222N mutation in the receptor-binding site of HA, which is associated with more severe disease. The oseltamivir and zanamivir resistance mutation H275Y in NA was detected in 2% of influenza A(H1N1)pdm09 viruses. No oseltamivir and zanamivir resistance mutations in NA were detected in all influenza A(H3N2) and B viruses tested. In all investigated influenza A(H1N1)pdm09 and A(H3N2) viruses the adamantane resistance mutation S31N in M2 was identified. Conclusions. The detection of amino acid substitutions in HA antigenic sites and resistance mutations in NA and M2 confirms the evolution of influenza viruses and the need for continuous genetic surveillance.

GEOCHEMICAL ANALYSES OF EOCENE OILS IN DEEPLY BURIED SANDSTONE RESERVOIRS IN THE DONGYING DEPRESSION, BOHAI BAY BASIN, NE CHINA

We report the results of organic geochemical analyses of 19 crude oil samples from reservoir sandstones in the 4th Member of the Eocene Shahejie Formation from wells in the Minfeng Sag, Dongying Depression, Bohai Bay Basin (NE China). In addition, 42 Shahejie Formation core samples of dark‐coloured mudstones, including 28 extracts, were analysed. Geochemical data included Rock‐Eval measurements, gas chromatography, GC‐MS and diamondoid analyses.Maceral analyses showed that mudstones in the 4th Member of the Shahejie Formation (“Es4”) contain Types I and II1 kerogen. The member can be divided into upper (Es4s) and lower (Es4x) intervals. Oil‐prone Es4s rock samples have good to excellent hydrocarbon‐generating potential based on calculated initial TOC values; Rock‐Eval Tmax values indicate that they are sufficiently mature for hydrocarbon generation. Analytical results suggest that both Es4s and Es4x mudrocks are potential source rocks for oils produced at fields in the Minfeng Sag.Analysed crude oils from the Minfeng Sag were classified into three genetic groups. Group I oils are mature to highly mature and have undergone a moderate degree of thermal cracking. They are characterized by a low β‐carotane/nC25 ratio and C30 4‐methylsterane index (4MI); high values of oleanane index (oleanane /C30‐hopane), C27 diasterane/C27 regular sterane (C27Dia/C27), regular sterane/17α hopane and gammacerane/C30 hopane (G/H); and medium pristane/phytane ratios (Pr/Ph). This suggests that Group I oils are mostly derived from source rocks in the upper part of the Es4x unit which are interbedded with evaporites. Group II oils are mature and have high 4MI and Pr/Ph ratios, low oleanane index, regular sterane/17α hopane and C27Dia/C27 ratios, and mediumβ‐carotane/nC25 and G/H. These features are similar to those of Es4s source rocks, indicating their genetic correlation. Group III oils show the lowest maturity and highβ‐carotane/nC25 and regular sterane/17α hopane, and low oleanane index, Pr/Ph and 4MI. Previously‐published data indicates that oils similar to those in Group III were mainly sourced by Es4s mudstones.

Exploring and Accounting for Genetically Driven Effect Heterogeneity in Mendelian Randomization

ABSTRACTMendelian randomization (MR) is a framework to estimate the causal effect of a modifiable health exposure, drug target or pharmaceutical intervention on a downstream outcome by using genetic variants as instrumental variables. A crucial assumption allowing estimation of the average causal effect in MR, termed homogeneity, is that the causal effect does not vary across levels of any instrument used in the analysis. In contrast, the science of pharmacogenetics seeks to actively uncover and exploit genetically driven effect heterogeneity for the purposes of precision medicine. In this study, we consider a recently proposed method for performing pharmacogenetic analysis on observational data—the Triangulation WIthin a STudy (TWIST) framework—and explore how it can be combined with traditional MR approaches to properly characterise average causal effects and genetically driven effect heterogeneity. We propose two new methods which not only estimate the genetically driven effect heterogeneity but also enable the estimation of a causal effect in the genetic group with and without the risk allele separately. Both methods utilise homogeneity‐respecting and homogeneity‐violating genetic variants and rely on a different set of assumptions. Using data from the ALSPAC study, we apply our new methods to estimate the causal effect of smoking before and during pregnancy on offspring birth weight in mothers whose genetics mean they find it (relatively) easier or harder to quit smoking.

Exome sequencing of 20,979 individuals with epilepsy reveals shared and distinct ultra-rare genetic risk across disorder subtypes.

Identifying genetic risk factors for highly heterogeneous disorders like epilepsy remains challenging. Here, we present the largest whole-exome sequencing study of epilepsy to date, with >54,000 human exomes, comprising 20,979 deeply phenotyped patients from multiple genetic ancestry groups with diverse epilepsy subtypes and 33,444 controls, to investigate rare variants that confer disease risk. These analyses implicate seven individual genes, three gene sets, and four copy number variants at exome-wide significance. Genes encoding ion channels show strong association with multiple epilepsy subtypes, including epileptic encephalopathies, generalized and focal epilepsies, while most other gene discoveries are subtype-specific, highlighting distinct genetic contributions to different epilepsies. Combining results from rare single nucleotide/short indel-, copy number-, and common variants, we offer an expanded view of the genetic architecture of epilepsy, with growing evidence of convergence among different genetic risk loci on the same genes. Top candidate genes are enriched for roles in synaptic transmission and neuronal excitability, particularly postnatally and in the neocortex. We also identify shared rare variant risk between epilepsy and other neurodevelopmental disorders. Our data can be accessed via an interactive browser, hopefully facilitating diagnostic efforts and accelerating the development of follow-up studies.

Oral Problems in Brazilian Individuals with Rare Genetic Diseases That Affect Skeletal Development.

The present study aimed to compare the prevalence of oral problems between individuals with rare genetic diseases that affect skeletal development and individuals without rare diseases. A cross-sectional study was conducted with 210 individuals between two and fifty-four years of age: 105 with rare genetic diseases (27 with mucopolysaccharidosis [MPS] and 78 with osteogenesis imperfecta [OI]) and 105 without rare diseases. The rare genetic disease group was recruited from hospital units that provide care for patients with MPS and OI in five states of Brazil, and the other group was recruited from the same location. The participants were examined with regards to malocclusion, dental anomalies, dental caries, and gingivitis. A questionnaire was administered addressing individual, sociodemographic, and behavioral characteristics as well as dental history. A descriptive analysis was performed, followed by unadjusted and adjusted binary logistic regression analyses. The mean age was 14.1 ± 12.2 years. Individuals with a rare disease were 12.9-fold more likely to have some type of oral problem (95% CI: 3.7-44.7) compared to the group without rare diseases. The prevalence of oral problems was higher among Brazilians with MPS and OI compared to normotypical individuals.