Informative Markers Research Articles

A New Genus of the Microascaceae (Ascomycota) Family from a Hypersaline Lagoon in Spain and the Delimitation of the Genus Wardomyces.

The Saladas de Sástago-Bujaraloz is an endorheic and arheic complex of lagoons located in the Ebro Basin and protected by the Ramsar Convention on Wetlands. Due to the semi-arid climate of the region and the high salinity of their waters, these lagoons constitute an extreme environment. We surveyed the biodiversity of salt-tolerant and halophilic fungi residents of the Laguna de Pito, a lagoon belonging to this complex. Therefore, we collected several samples of water, sediments, and soil of the periphery. Throughout the study, we isolated 21 fungal species, including a strain morphologically related to the family Microascaceae. However, this strain did not morphologically match any of genera within this family. After an in-depth morphological characterization and phylogenetic analysis using a concatenated sequence dataset of four phylogenetically informative molecular markers (the internal transcribed spacer region (ITS) of the nuclear ribosomal DNA (nrDNA); the D1-D2 domains of the 28S gene of the nuclear ribosomal RNA (LSU); and a fragment of the translation elongation factor 1-alpha (EF-1α) and the β-tubulin (tub2) genes), we established the new genus Dactyliodendromyces, with Dactyliodendromyces holomorphus as its species. Additionally, as a result of our taxonomic study, we reclassified the paraphyletic genus Wardomyces into three different genera: Wardomyces sensu stricto, Parawardomyces gen. nov., and Pseudowardomyces gen. nov., with Parawardomyces ovalis (formerly Wardomyces ovalis) and Pseudowardomyces humicola (formerly Wardomyces humicola) as the type species of their respective genera. Furthermore, we propose new combinations, including Parawardomyces giganteus (formerly Wardomyces giganteus) and Pseudowardomyces pulvinatus (formerly Wardomyces pulvinatus).

Abstract 3409: AGEing and lifestyle after a cancer diagnosis: A balanced equilibrium for survivorship

Abstract In the US, over 18 million people are living with a cancer diagnosis and that number may double by 2050. There is a need to unite research across the cancer continuum to address the needs of cancer survivors to ensure optimal quality of life and improve mortality outcomes. Health constructs that influence cancer survivorship are multifactorial, highly dynamic, and vary across the lifespan. This makes assigning their impact on the well-being and future outcomes of cancer survivors challenging. As a pathophysiological process that lies at the intersection between societal, environmental, and biological constructs, it is proposed that the irreversible accumulation of metabolites called advanced glycation end products (AGEs) can inform on quality of life and mortality outcomes for cancer survivors. It is proposed that AGE accumulation as a result of societal, environmental, and biological constructs overwhelm the fragile equilibrium that maintains AGE homoeostasis to impact tumor biology and cancer outcomes. The relationships between health constructs and AGE exposure are epitomized by nutritional behavior. The consumption of cheaper unhealthier often ultra-processed foods are inherently AGE laden and the excessive consumption of foods high in fats and sugars that promote obesity and increase cancer risk readily provide reactive intermediates that fuel AGE formation in cells and tissues. Our collaborative epidemiological studies assign high levels of AGE consumption with increased breast cancer risk, aggressiveness, and mortality, which is supported by translational studies showing that circulating AGE levels in breast cancer patients correlate with worse disease-free survival and other poor prognosis indicators. Critically, this group has also shown that chronic AGE consumption by mice increases prostate tumor growth (p<0.001), and causes a rapid progression through prostate intra-epithelial neoplasia (p=0.049), adenocarcinoma (p=0.042) and metastasis (p=0.001). Consumption of the high AGE diet caused a regulatory program of stromal activation conducive for tumor growth. As a bio-social determinant of health AGE accumulation and its pathogenic effects serve as informative and/or functional markers indicative of the current health status and well-being of cancer survivors and may inform of potential future outcomes. Our studies show that physical activity and dietary intervention (cardiac rehabilitation) reduced systemic AGE levels in breast cancer survivors. Therefore, prevention and control interventions aimed at reducing AGE exposure represent viable strategies for improving quality of life and disease recurrence for cancer survivors. This research was made possible in part by Grant Numbers R01-CA259415, R01-CA245143, R21-CA194469, and U54-CA210962 from NIH-NCI. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of NIH. Citation Format: David P. Turner, Bradley A. Krisanits, Marvella E. Ford, Lindsay L. Peterson, Susan E. Steck, Paula D. Bos, Victoria J. Findlay. AGEing and lifestyle after a cancer diagnosis: A balanced equilibrium for survivorship [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3409.

Abstract 4801: Clinical polygenic model to stratify risk of any, metastatic, and fatal prostate cancer in a randomized controlled trial of precision screening

Abstract Introduction: Lifetime risk of prostate cancer (PCa) is strongly associated with three factors: ancestry, family history, and genetics. We previously developed a polygenic hazard score (PHS) for PCa comprised of 290 common genetic variants (PHS290). When accounting for family history and ancestry (self-reported or genetically determined), PHS290 remained a powerful independent predictor of age at PCa diagnosis, metastatic PCa diagnosis, and PCa death. Additional variants associated with PCa susceptibility or benign elevation of prostate-specific antigen (PSA) have since been published. Here, we evaluate their impact on lifetime risk predictions for metastatic and fatal PCa and develop an updated polygenic score. This score will inform the design of the Prostate Cancer, Genetic Risk, and Equitable Screening Study (ProGRESS, ClinicalTrials.gov ID NCT05926102), a nationwide randomized controlled trial evaluating precision PCa screening in the VA healthcare system. Methods: We utilized a machine learning approach to update the PHS. Over 450 variants associated with PCa, aggressive PCa, benign prostatic hyperplasia, or benign PSA elevation were evaluated for inclusion. First, we identified pairs of variants with highly correlated genotype (defined as R2 > 0.95) and utilized univariable Cox proportional hazards models (using age at diagnosis of PCa) to exclude one variant from each pair. We then evaluated all remaining candidate variants for inclusion in a new PHS using a LASSO-regularized Cox proportional hazards model. We combined the new PHS with clinical predictors (ancestry and family history) to create a comprehensive, quantitative polygenic score in a diverse, population-based cohort of n=590,750 (Million Veteran Program). Both self-reported and genetic ancestry (based on 2,309 ancestry informative markers) were assessed. We estimated hazard ratios (HRs) to compare men with high versus low polygenic score and evaluated absolute predictions of any, metastatic, and fatal PCa. Results: The updated polygenic score included 356 variants, as well as family history and genetic ancestry. When comparing the highest to the lowest quintile of the population for polygenic score, the HRs for any PCa, metastatic PCa, and fatal PCa were 5.6, 5.8, and 5.2 respectively. These HRs are all greater than those achieved with PHS290, which yielded 5.2, 4.9, and 4.4 respectively. Risk stratification improved within each ancestry group, including within the >100,000 participants of African ancestry—a group known to have elevated risk of fatal PCa. Absolute risk prediction was accurate for both metastatic and fatal PCa. Conclusion: The polygenic score accurately predicts risk of metastatic and fatal PCa in multiple ancestry groups. A clinical polygenic model has potential utility for precision PCa screening and will now be evaluated prospectively in the ProGRESS trial. Citation Format: Anna M. Dornisch, Roshan Karunamuni, Kara N. Maxwell, Julie Lynch, Isla P. Garraway, Adam Kibel, Charles A. Brunette, Morgan E. Danowski, Kyung M. Lee, Scott L. DuVall, J M. Gaziano, Brent S. Rose, Richard L. Hauger, Jason L. Vassy, Tyler M. Seibert. Clinical polygenic model to stratify risk of any, metastatic, and fatal prostate cancer in a randomized controlled trial of precision screening [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4801.

Abstract 7129: DNA polymerase beta expression in head & neck cancer modulates the poly-ADP-ribose-mediated replication checkpoint

Abstract Head and Neck Squamous Cell Carcinoma (HNSCC) impose a significant health burden, necessitating innovative therapeutic strategies to enhance treatment efficacy. Current standard treatments, including surgery, radiation therapy, and chemotherapy, often exhibit limited effectiveness and cause substantial side effects. This underscores the critical need for novel therapies that selectively target cancer cells, sparing normal tissue. Survival from HNSCC is poor, and importantly, a racial disparity between African Americans (AfAm) and European Americans (EuAm) has been known for some time. Ancestry Informative Markers (AIMs) are associated with altered mRNA expression of Polβ where higher expression of Polβ was observed among AfAm patients in comparison to EuAm patients. Our research focuses on DNA polymerase beta (Polβ) and its role in replication stress and response to chemotherapy and DNA damage response modifiers. Elevated expression of Polβ is linked to increased DNA damage and genomic instability, contributing to treatment resistance. In this regard, our investigations reveal a regulatory role for base excision repair (BER) proteins, including Polβ, in the cellular response to inhibitors of poly(ADP-ribose) glycohydrolase (PARG), an enzyme involved in poly(ADP-ribose) (PAR) degradation. Inhibition of PARG triggers a robust intra-S phase response, activating ATR and CHK1 signaling. Exploiting the synthetic lethality between PARG inhibition and ATR/CHK1 inhibition, we have demonstrated the ability to overcome Polβ overexpression mediated treatment resistance in HNSCC cells. Specifically, our in vitro studies demonstrate that the response to a combination of an ATR inhibitor and PARG inhibitor is impacted by Polβ expression in HNSCC cells, with synergistic effects surpassing the efficacy of the individual inhibitors. Similarly, the combination of a CHK1 inhibitor and PARG inhibitor proves effective in cells with elevated Polβ expression, offering a potential dual therapeutic strategy. These combinations exhibit promising potential for HNSCC treatment when Polβ expression is elevated. In conclusion, our findings propose a novel therapeutic paradigm for HNSCC, employing combination therapy with ATR or CHK1 inhibitors and PARG inhibitors. This approach offers a targeted strategy, presenting a promising avenue for the development of more effective and less toxic treatment modalities in the management of HNSCC and may help overcome resistance from elevated expression of Polβ. Citation Format: Md Maruf Khan, Anusha Angajala, Denise Y. Gibbs, Jeffrey C. Liu, Camille Ragin, Robert W. Sobol. DNA polymerase beta expression in head & neck cancer modulates the poly-ADP-ribose-mediated replication checkpoint [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7129.

Genetic evaluations of dairy goats with few pedigree data: different approaches to use molecular information.

One of the limitations of implementing animal breeding programs in small-scale or extensive production systems is the lack of production records and genealogical records. In this context, molecular markers could help to gain information for the breeding program. This study addresses the inclusion of molecular data into traditional genetic evaluation models as a random effect by molecular pedigree reconstruction and as a fixed effect by Bayesian clustering. The methods were tested for lactation curve traits in 14 dairy goat herds with incomplete phenotypic data and pedigree information. The results showed an increment of 37.3% of the relationships regarding the originals with MOLCOAN and clustering into five genetic groups. Data leads to estimating additive variance, error variance, and heritability with four different models, including pedigree and molecular information. Deviance Information Criterion (DIC) values demonstrate a greater fitting of the models that include molecular information either as fixed (genetic clusters) or as random (molecular matrix) effects. The molecular information of simple markers can complement genetic improvement strategies in populations with little information.

Generation and genetic analysis of a rainbow trout (Oncorhynchus mykiss) clonal line produced by gynogenesis

The efficiency of heat-shock treatments for producing gynogenetic double haploids was evaluated using a rainbow trout (Oncorhynchus mykiss) strain locally adapted in Brazil (2002 broodstock). Eleven and 15 females produced by conventional reproduction (FC) or meiotic gynogenesis (FG) were used as egg donors, respectively. Oocytes from each female were randomly divided into five uneven lots which were submitted to different treatments: (C2n) Normal diploid control, (H) Haploid control, (G-Me) Meiotic gynogenetic, (G-Mi) Mitotic gynogenetic, and (4 n) Control of suppression of the 1st cell cleavage. Homozygous yellow-colored (Dominant albino - DA) males were used as semen donors. Gynogenesis was induced by insemination of eggs with DA semen genetically inactivated by ultraviolet irradiation. Diploidization of gynogenic individuals was induced by an early heat shock to block 2nd polar body extrusion (G-Me), or a late heat shock to suppress first mitosis (G-Mi). Overall mean survival rates to eyed-egg and first feeding stages of treated groups, relative to respective C2n control group were: 19.21 and 14.90%, 13.02 and 8.09%, and 29.94 and 16.48%, for treatments G-Me, G-Mi and 4 n, respectively. When compared with C2n, all treatments showed lower survival rates at both stages. Survival of G-Me and G-Mi progeny from FG females were significantly higher when compared to progeny from FC females for both stages. Progenies from two different females observed to be 100% homozygous in analyzed informative microsatellite markers were used in subsequent cycles of gynogenic reproduction. One line originally derived from a single gynogenic female was reproduced for nine successive generations of meiotic gynogenetic reproduction. Forty animals from the ninth successive generation of gynogenetic reproduction were analyzed with a low-density SNP (Single Nucleotide Polymorphism) panel. All individuals were observed to be homozygous for identical alleles at all SNPs, therefore indicating that the established mitotic gynogenetic line is composed of 100% clonal individuals.

Detection of QTLs controlling flowering in a cross-pollinated F1 population of Miscanthus sinensis

Miscanthus is a perennial rhizomatous grass belonging to Andropogoneae, which is now used as lignocellulosic biomass crop. Miscanthus has a short history of domestication, so further breeding effort for improved biomass production is needed. Flowering plays a critical role in controlling vegetative growth and physiology of plant, so this study focused on finding quantitative trait locus controlling flowering of Miscanthus for use in marker assisted breeding. A cross-pollinated M. sinensis F1 population consisted of 278 progenies was produced, transplanted to the field and assessed in their flowering traits. Julian dates of flag leaf extension, first heading, half heading, first flowering, and half flowering were assessed in 2019, the third year after transplanting when Miscanthus was well established. The average Julian dates of the flowering traits were 198±9, 224±14, 233±14, 239±15 and 253±12, respectively, and showed a proximal normal distribution. Genotype by sequencing conducted by Illumina-hiseq using leaf DNA samples revealed the genetic map consisted of 1988 SNPs with average distance of 1.35 cM. Nine QTLs controlling flowering were detected exceeded 60% of LOD score threshold. These QTLs were neighboring 16 SNP markers, 5 of which were contained in known functional genes including RGL2 (gibberellin pathway regulation). Genetic map and marker information acquired through this study, including either annotated or not annotated markers, are expected to help understand and help breeding new Miscanthus in the future with desired flowering.

An Adaptive Radon-Transform-Based Marker Detection and Localization Method for Displacement Measurements Using Unmanned Aerial Vehicles.

UAVs have been widely used in deformation monitoring because of their high availability and flexibility. However, the quality of UAV images is affected by changing attitude and surveying environments, resulting in a low monitoring accuracy. Cross-shaped markers are used to improve the accuracy of UAV monitoring due to their distinct center contrast and absence of eccentricity. However, existing methods cannot rapidly and precisely detect these markers in UAV images. To address these problems, this paper proposes an adaptive Radon-transform-based marker detection and localization method for UAV displacement measurements, focusing on two critical detection parameters, namely, the radius of marker information acquisition and the edge width of the cross-shaped scoring template. The experimental results show that the marker detection rate is 97.2% under different combinations of flight altitudes, radius ratios of marker information acquisition, and marker sizes. Furthermore, the root mean square error of detection and localization is 0.57 pixels, significantly surpassing the performance and accuracy of other methods. We also derive the critical detection radius and appropriate parameter combinations for different heights to further improve the practicality of the method.

Analysis of the relationship of various pathologies with the degree of multifractality of electrical activity of the brain

The review is devoted to the analysis of the relationship between dynamic changes in patterns of electrical activity of the brain during the occurrence of mental disorders in the form of paranoid schizophrenia and depression and in patterns of brain activity in cardiovascular pathology associated with permanent atrial fibrillation, as well as indicators of multifractality of the studied patterns. To assess these indicators of electroencephalographic patterns, we describe a method of multifractal analysis based on the search for maxima of wavelet coefficient modules, and to isolate the fractal component of the signal in the power spectrum we describe a method of autospectral analysis with irregular resampling. It has been shown that the main differences between the multifractal properties of the electrical activity of the brain in health and in pathology are the different widths of the multifractality spectrum and its location, associated with different types of sequential pattern values. In this regard, the multifractality indicators can serve as informative markers of neuronal disorders and can be included in a set of tests for studying various pathologies.

Association study of morpho-phenological traits in quinoa (Chenopodium quinoa Willd.) using SSR markers.

In this study, the genetic and molecular diversity of 60 quinoa accessions was assessed using agronomically important traits related to grain yield as well as microsatellite (SSR) markers, and informative markers linked to the studied traits were identified using association study. The results showed that most of the studied traits had a relatively high diversity, but grain saponin and protein content showed the highest diversity. High diversity was also observed in all SSR markers, but KAAT023, KAAT027, KAAT036, and KCAA014 showed the highest values for most of the diversity indices and can be introduced as the informative markers to assess genetic diversity in quinoa. Population structure analysis showed that the studied population probably includes two subclusters, so that out of 60 quinoa accessions, 29 (48%) and 23 (38%) accessions were assigned to the first and second subclusters, respectively, and eight (13%) accessions were considered as the mixed genotypes. The study of the population structure using Structure software showed two possible subgroups (K = 2) in the studied population and the results of the bar plot confirmed it. Association study using the general linear model (GLM) and mixed linear model (MLM) identified the number of 35 and 32 significant marker-trait associations (MTAs) for the first year (2019) and 37 and 35 significant MTAs for the second year (2020), respectively. Among the significant MTAs identified for different traits, the highest number of significant MTAs were obtained for grain yield and 1000-grain weight with six and five MTAs, respectively.

Mapping the genetic architecture of low-temperature stress tolerance in citron watermelon.

Sweet-fleshed watermelon (Citrullus lanatus) is an important vegetable crop of the tropical origin. It is widely grown and consumed around the world for its hydration and nutritional quality values. Low-temperature stress can affect early planting, seedling establishment, and expansion of crop production to new areas. A collection of 122 citron watermelon (Citrullus amarus) accessions were obtained from the USDA's National Plant Germplasm Repository System gene bank in Griffin, GA. The accessions were genotyped using whole genome resequencing to generate single nucleotide polymorphisms (SNPs) molecular markers and screened under cold-stressed and non-stressed control conditions. Four low-temperature stress tolerance related traits including shoot biomass, vine length, maximum quantum efficiency of photosystem II, and chlorophyll content were measured under cold-stressed and non-stressed control treatment conditions. Correlation analysis revealed the presence of positive relationships among traits. Broad-sense heritability for all traits ranged from 0.35 to 0.73, implying the presence of genetic contributions to the observed phenotypic variation. Genomic regions underlying these traits across several citron watermelon chromosomes were identified. Four low-temperature stress tolerance related putative candidate genes co-located with the peak SNPs from genome-wide association study. These genomic regions and marker information could potentially be used in molecular breeding to accelerate genetic improvements for low-temperature stress tolerance in watermelon.

Evaluation of serum and urine biomarkers for severe COVID-19.

The new coronavirus disease, COVID-19, poses complex challenges exacerbated by several factors, with respiratory tissue lesions being notably significant among them. Consequently, there is a pressing need to identify informative biological markers that can indicate the severity of the disease. Several studies have highlighted the involvement of proteins such as APOA1, XPNPEP2, ORP150, CUBN, HCII, and CREB3L3 in these respiratory tissue lesions. However, there is a lack of information regarding antibodies to these proteins in the human body, which could potentially serve as valuable diagnostic markers for COVID-19. Simultaneously, it is relevant to select biological fluids that can be obtained without invasive procedures. Urine is one such fluid, but its effect on clinical laboratory analysis is not yet fully understood due to lack of study on its composition. Methods used in this study are as follows: total serum protein analysis; ELISA on moderate and severe COVID-19 patients' serum and urine; bioinformatic methods: ROC analysis, PCA, SVM. The levels of antiAPOA1, antiXPNPEP2, antiORP150, antiCUBN, antiHCII, and antiCREB3L3 exhibit gradual fluctuations ranging from moderate to severe in both the serum and urine of COVID-19 patients. However, the diagnostic value of individual anti-protein antibodies is low, in both blood serum and urine. On the contrary, joint detection of these antibodies in patients' serum significantly increases the diagnostic value as demonstrated by the results of principal component analysis (PCA) and support vector machine (SVM). The non-linear regression model achieved an accuracy of 0.833. Furthermore, PCA aided in identifying serum protein markers that have the greatest impact on patient group discrimination. The study revealed that serum serves as a superior analyte for describing protein quantification due to its consistent composition and lack of organic salts and drug residues, which can otherwise affect protein stability.

Diagnostic value of clinical-instrumental and hematological indicators in predicting complications of the hospital period of STEMI in conditions of chronic stress caused by wartime

The aim – to develop a diagnostic system that takes into account the peculiarities of clinical, instrumental and laboratory indicators in patients with STEMI against the background of wartime and will allow to objectify a tendency to a more difficult hospital course of ACS.Materials and methods. We studied a cohort of patients (n=133 individuals, 77.4 % men, average age 61.8±0.9 years) with STEMI, part of which (group 1) was hospitalized from February to May 2019 (n=87), while another part of which (group 2) was hospitalized in the period from February 24, 2022 to March 2023 (n=46) within the first 24 hours from the development of symptoms of the disease (average time of admission 5.2±0.4 hours). The groups were compared according to the clinical and anamnestic and laboratory parameters of the first day.Results and discussion. It was found that in the Ukrainian population during wartime, patients with STEMI are admitted to the hospital later, have a more burdensome history of cerebrovascular diseases, a greater number of significant coronary stenoses, a higher percentage of smokers, and also have higher heart rate levels upon admission, ESR, triglycerides, leukocytes (at the expense of lymphocytes and monocytes), as well as platelets (with lower indicators of their size inhomogeneity). Also, invasive treatment of these lesions leads to slightly worse results on the TIMI and MBG scales. Informativeness of hematology analysis indicators and other markers of inflammation/stress on the first day of STEMI in wartime was evaluated for predicting the risk of an complicated course of the hospital period (development of cardiac death, signs of LVEF, ventricular tachyarrhythmias, stent thrombosis, acute renal dysfunction, recurrence of ACS/angina). It was found that predictors of the undesirable course of STEMI during wartime are: heart rate > 70/min, ESR > 10 mm/h, glucose level > 8.5 mmol/l, leukocytes > 13 · 109/l, lymphocytes > 2 · 109/l, platelets > 270 · 109/l, large (>12 fl) platelets < 27 %, triglycerides > 1.3 mmol/l, as well as combined criteria made up of these indicators. Thus, the 6-component score (heart rate, ESR, glucose, levels of leukocytes, lymphocytes, and platelets) had an area under the ROC curve of 0.87 (for values ​​> 30 units – BP 6.39 (2.16–18.9), p<0.0001) when determining the risk of an undesirable course of ACS in patients during wartime. These predictors are specific to the stress-induced effects of war and are not informative in peacetime STEMI patients.Conclusions. The coexistence of acute stress caused by STEMI with chronic exposure to stress-associated wartime factors can worsen the course of the hospital period of STEMI, which is associated with an increase in heart rate, ESR, glucose level, leukocytes, lymphocytes, triglycerides, platelets with a decrease in their inhomogeneity in size. Taking into account these features allows predicting the risk of a complicated course of the hospital period of the STEMI in wartime.

Validation of sorghum quality control (QC) markers across African breeding lines.

Sorghum [Sorghum bicolor (L.) Moench] is a cereal crop of critical importance in the semi-arid tropics, particularly in Africa where it is second only to maize (Zea mays L.) by area of cultivation. The International Crops Research Institute for the Semi-Arid Tropics sorghum breeding program for Eastern and Southern Africa is the largest in the region and develops improved varieties for target agro-ecologies. Varietal purity and correct confirmation of new crosses are essential for the integrity and efficiency of a breeding program. We used 49 quality control (QC) kompetitive allele-specific PCR single nucleotide polymorphism (SNP) markers to genotype 716 breeding lines. Note that 46 SNPs were polymorphic with the top 10 most informative revealing polymorphism information content (PIC), minor allele frequency (MAF), and observed heterozygosity (Ho ) of 0.37, 0.43, and 0.02, respectively, and explaining 45% of genetic variance within the first two principal components (PC). Thirty-nine markers were highly informative across 16 Burkina Faso breeding lines, out of which the top 10 revealed average PIC, MAF, and Ho of 0.36, 0.39, and 0.05, respectively. Discriminant analysis of principal components done using top 30 markers separated the breeding lines into five major clusters, three of which were distinct. Six of the top 10 most informative markers successfully confirmed hybridization of crosses between genotypes IESV240, KARIMTAMA1, F6YQ212, and FRAMIDA. A set of 10, 20, and 30 most informative markers are recommended for routine QC applications. Future effort should focus on the deployment of these markers in breeding programs for enhanced genetic gain.

Патогенетические аспекты рецидивирующей эндометриальной гиперплазии без атипии у женщин репродуктивного возраста

Aim: to determine the most informative immunohistochemical markers of recurrent endometrial hyperplasia without atypia in women of childbearing age. Methods. Prospective analysis of 89 patients of childbearing age was performed at the Department of Obstetrics and Gynecology with Perinatology, Medical Institute of the Peoples' Friendship University of Russia. During the study the patients were divided into two cohorts based on the EH course: the index group (n=45) was represented by patients with the morphologically verified recurrent endometrial hyperplasia without atypia (one or more episodes within a year), the control group (n=44) was represented by patients with the newly diagnosed endometrial hyperplasia without atypia. The average age of patients in the studied cohort was 44±3.0 years (comparison group – 42±2.0 years). Results. Immunohistochemical markers of recurrence were identified during the study: high Ki-67 expression (p<0.05), low Bcl-2 expression (p<0.05) that enhanced proliferative and reduce antiproliferative processes in the endometrium. Immunohistochemical signs of chronic endometritis (СD138+) were found in 40% of patients suffering from recurrent endometrial hyperplasia (in 18.2% of controls). It should be also noted that there was local hyperestrogenism associated with high expression of estrogen in the glandular epithelium and stroma. Conclusion. Thus, the Ki-67 marker expression and low Bcl-2 expression contribute to recurrence of endometrial hyperplasia without atypia. Furthermore, the combination of endometrial hyperplasia and morphologically verified chronic endometritis provides a further predictor of the endometrial proliferative process recurrence. Immunohistochemistry makes it possible to predict not only the risk of recurrent endometrial hyperplasia, but also the disease course. However, there is currently no universal marker allowing one to predict the chance of hyperplasia diagnosis and recurrence. Design: a comparative prospective study.

Identification and genetic diversity analysis of broomrape in Xinjiang, China

BackgroundAs a holoparasitic weed, broomrape has seriously threatened the production of economically important crops, such as melon, watermelon, processed tomato, and sunflower, in Xinjiang in recent years. However, the distribution and genetic diversity of broomrape populations in Xinjiang are not clear at present, which hinders their prevention and control. The purpose of this study was to identify the main species and the genetic differentiation structure of the broomrape population in Xinjiang.Methods and resultsIn the present study, 93 samples from different geographic regions of Xinjiang were collected to identify the species based on ITS and plastid rps2 regions, and the samples were also used to analyze the genetic diversity based on ISSR markers. The results showed that broomrape is not monophyletic in Xinjiang and consists of two major clades (Orobanche cf. aegyptiaca and O. cernua) and three subclades (O. cf. aegyptiaca var. tch, O. cf. aegyptiaca var. klz, and O. cernua.var. alt) based on phylogenetic analysis. Furthermore, the results of the genetic diversity analysis indicated that the average polymorphic information content and marker index were high values of 0.58 and 7.38, respectively, showing the efficiency of the ISSR markers in detecting polymorphism among the broomrape population studied. Additionally, the 11 selected primers produced 154 repeatable polymorphic bands, of which 150 were polymorphic. The genetic diversity of the samples was 37.19% within populations and 62.81% among the populations, indicating that the main genetic differentiation occurred among the populations. There was less gene exchange between populations, with a gene flow index (Nm) of 0.2961 (< 1). The UPGMA dendrogram indicated that most populations with similar geographical conditions and hosts were clustered first, and then all samples were separated into two major groups and seven subclusters.ConclusionThe broomrapes are mainly O. cf. aegyptiaca and O. cernua in Xinjiang, which were separated into two major groups and seven subclusters based on ISSR markers. Our results provide a theoretical basis for breeding broomrape-resistant varieties.

Accurate identification of Helicoverpa armigera-Helicoverpa zea hybrids using genome admixture analysis: implications for genomic surveillance.

Helicoverpa armigera, the cotton bollworm moth, is one of the world's most important crop pests, and is spreading throughout the New World from its original range in the Old World. In Brazil, invasive H. armigera has been reported to hybridize with local populations of Helicoverpa zea. The correct identification of H. armigera-H. zea hybrids is important in understanding the origin, spread and future outlook for New World regions that are affected by outbreaks, given that hybridization can potentially facilitate H. zea pesticide resistance and host plant range via introgression of H. armigera genes. Here, we present a genome admixture analysis of high quality genome sequences generated from two H. armigera-H. zea F1 hybrids generated in two different labs. Our admixture pipeline predicts 48.8% and 48.9% H. armigera for the two F1 hybrids, confirming its accuracy. Genome sequences from five H. zea and one H. armigera that were generated as part of the study show no evidence of hybridization. Interestingly, we show that four H. zea genomes generated from a previous study are predicted to possess a proportion of H. armigera genetic material. Using unsupervised clustering to identify non-hybridized H. armigera and H. zea genomes, 8511 ancestry informative markers (AIMs) were identified. Their relative frequencies are consistent with a minor H. armigera component in the four genomes, however its origin remains to be established. We show that the size and quality of genomic reference datasets are critical for accurate hybridization prediction. Consequently, we discuss potential pitfalls in genome admixture analysis of H. armigera-H. zea hybrids, and suggest measures that will improve such analyses.

Identification of environment-insensitive genes for oil content by combination of transcriptome and genome-wide association analysis in rapeseed.

The primary objective of rapeseed breeding is to enhance oil content, which is predominantly influenced by environmental factors. However, the molecular mechanisms underlying the impact of these environmental factors on oil accumulation remain inadequately elucidated. In this study, we used transcriptome data from two higher (HOC) and two lower oil content (LOC) inbred lines at 35days after pollination (DAP) to investigate genes exhibiting stable expression across three different environments. Meanwhile, a genome-wide association study (GWAS) was utilized to detect candidate genes exhibiting significant associations with seed oil content across three distinct environments. The study found a total of 405 stable differentially expressed genes (DEGs), including 25 involved in lipid/fatty acid metabolism and 14 classified as transcription factors. Among these genes, BnBZIP10-A09, BnMYB61-A06, BnAPA1-A08, BnPAS2-A10, BnLCAT3-C05 and BnKASIII-C09 were also found to exhibit significant associations with oil content across multiple different environments based on GWAS of 50 re-sequenced semi-winter rapeseed inbred lines and previously reported intervals. Otherwise, we revealed the presence of additive effects among BnBZIP10-A09, BnKASIII-C09, BnPAS2-A10 and BnAPA1-A08, resulting in a significant increase in seed oil content. Meanwhile, the majority of these stable DEGs are interconnected either directly or indirectly through co-expression network analysis, thereby giving rise to an elaborate molecular network implicated in the potential regulation of seed oil accumulation and stability. The combination of transcription and GWAS revealed that natural variation in six environment-insensitive gene regions exhibited significant correlations with seed oil content phenotypes. These results provide important molecular marker information for us to further improve oil content accumulation and stability in rapeseed.

Development of a novel five dye insertion/deletion (INDEL) panel for ancestry determination.

The use of genetic markers, specifically Short Tandem Repeats (STRs), has been a valuable tool for identifying persons of interest. However, the ability to analyze additional markers including Single Nucleotide Polymorphisms (SNPs) and Insertion/Deletion (INDELs) polymorphisms allows laboratories to explore other investigative leads. INDELs were chosen in this study because large panels can be differentiated by size, allowing them to be genotyped by capillary electrophoresis. Moreover, these markers do not produce stutter and are smaller in size than STRs, facilitating the recovery of genetic information from degraded samples. The INDEL Ancestry Informative Markers (AIMs) in this study were selected from the 1000 Genomes Project based on a fixation index (FST) greater than 0.50, high allele frequency divergence, and genetic distance. A total of 25 INDEL-AIMs were optimized and validated according to SWGDAM guidelines in a five-dye multiplex. To validate the panel, genotyping was performed on 155 unrelated individuals from four ancestral groups (Caucasian, African, Hispanic, and East Asian). Bayesian clustering and principal component analysis (PCA) were performed revealing clear separation among three groups, with some observed overlap within the Hispanic group. Additionally, the PCA results were compared against a training set of 793 samples from the 1000 Genomes Project, demonstrating consistent results. Validation studies showed the assay to be reproducible, tolerant to common inhibitors, robust with challenging casework type samples, and sensitive down to 125 pg. In conclusion, our results demonstrated the robustness and effectiveness of a 25 loci INDEL system for ancestry inference of four ancestries commonly found in the United States.

Specifics of determination of human biological age by blood samples using epigenetic markers

Our research focused on the selection of already known markers, as well as the search for other informative markers based on data made publicly available on the GEO NCBI platform (genome-wide DNA methylation projects using the Infinium Human Methylation 450K BeadChip (Illumina ©)). The main objective of the study was to demonstrate that the accuracy of determining the biological age of a person in the presence of chronic diseases using linear-dependent methylation markers is comparable to the accuracy of determining the biological age of a healthy person. Criminologists, as a rule, do not have information about the chronic diseases of a person who has left a biological trace at the scene (blood, for example). However, the lack of this information, as we have shown for some diseases, does not play a critical role in the precise determination of biological age. Additionally, an obstacle was removed when transferring the information content of markers from Infinium Human Methylation 450K BeadChip chips to SNaPshot technology. The analysis was carried out on a sample of 236 Belarusians, for whom the methylation profile for 7 Cpg markers is presented. It is shown that the information content of markers is preserved Our analysis shows the possibility of creating a universal test system for predicting biological age according to marker methylation. The system can be used in the work of most criminalists in the world with the same task.