Candidate Genes For Investigation Research Articles

Characterization of genetic diversity and identification of genetic loci associated with carbon allocation in N2 fixing soybean

BackgroundEfficient capture and use of resources is critical for optimal plant growth and productivity. Both shoot and root growth are essential for resource acquisition, namely light and CO2 by the shoot and water and mineral nutrients by roots. Soybean [Glycine max (L.) Merr.], one of the most valuable crops world-wide, uses an additional strategy, symbiotic N fixation (SNF), for N acquisition. SNF relies on development of specialized root organs known as nodules, which represent a distinct C sink. The genetic diversity of C partitioning in N fixing soybean to shoots, roots, and nodules has not been previously investigated but is valuable to better understand consequences of differential C allocation and to develop genetic resources, including identification of quantitative trait loci (QTLs).ResultsA diversity panel of 402 soybean genotypes was phenotyped outdoors in a deep-tube system without addition of mineral N to measure allocation of biomass to the shoot, root, and nodules, as well as to determine nodule number, mean nodule biomass, and total shoot N accumulation. Wide ranges in phenotypes were observed for each of these traits, demonstrating extensive natural diversity in C partitioning and SNF in soybean. Using a set of 35,647 single nucleotide polymorphism (SNP) markers, we identified 121 SNPs tagging 103 QTLs that include both 84 novel and 19 previously identified QTLs for the eight examined traits. A candidate gene search identified 79 promising gene models in the vicinity of these QTLs. Favorable alleles of QTLs identified here may be used in breeding programs to develop elite cultivars with altered C partitioning.ConclusionsThis study provides novel insights into the diversity of biomass allocation in soybean and illustrates that the traits measured here are heritable and quantitative. QTLs identified in this study can be used in genomic prediction models as well as for further investigation of candidate genes and their roles in determining partitioning of fixed C. Enhancing our understanding of C partitioning in plants may lead to elite cultivars with optimized resource use efficiencies.

Circulating YKL-40 levels but not CHI3L1 or TRIB1 gene variants predict long-term outcomes in patients with angiographically confirmed multivessel coronary artery disease

YKL-40 is significantly associated with the prevalence and severity of coronary artery disease (CAD). YKL-40 levels are significantly associated with variations in the CHI3L1 and TRIB1 genes. We investigated candidate genes for YKL-40 levels and evaluated the prognostic value of this biomarker and corresponding variants for long-term outcomes in patients with CAD. We included 4664 and 521 participants from the Taiwan Biobank (TWB) and CAD cohorts, respectively. Candidate variants for circulating YKL-40 levels were investigated using genome-wide association study (GWAS) data from the TWB cohort, and the results were validated in the CAD cohort. The primary endpoint was all-cause mortality. The secondary endpoint was major adverse cardiac events (MACEs), which included the composite endpoints of all-cause mortality, nonfatal acute coronary syndrome, hospitalization for heart failure, and nonfatal stroke. According to the GWAS data from the TWB cohort, three CHI3L1 variants (rs4950928, rs10399931, and rs872129) and one TRIB1 variant (rs6982502) were independently associated with YKL-40 levels. These findings were validated in the CAD cohort. The combined CHI3L1 and TRIB1 weighted genetic risk scores (WGRSs) were not associated with the long-term outcomes (median follow-up period of 3.7 years) in patients with CAD. Conversely, patients with YKL-40 levels in the upper tertile had the highest rates of all-cause mortality and MACEs (log-rank p = 9.58 × 10−8 for all-cause mortality and 1.34 × 10−7 for MACEs). Furthermore, YKL-40 levels predicted poor clinical outcomes only in patients with multivessel CAD (log-rank p = 3.0 × 10−6 for all-cause mortality and 1.10 × 10−5 for MACEs) and not in patients with single-vessel CAD. This study revealed that YKL-40 levels but not the combined CHI3L1 and TRIB1 WGRSs were found to be independent predictors of poor clinical outcomes in patients with multivessel CAD.

Metabolomic and transcriptomic analyses reveals candidate genes and pathways involved in secondary metabolism in Bergenia purpurascens

Bergenia purpurascens is an important medicinal, edible and ornamental plant. The lack of omics information hinders the study of its metabolic pathways and related genes. In order to investigate candidate genes and pathways involved in secondary metabolism in B. purpurascens, roots, stems and leaves of B. purpurascens were subjected to metabolomic and transcriptomic analyses in this study. A total of 351 differentially accumulated secondary metabolites were identified. We identified 120 candidate genes involved in phenylpropanoid and flavonoid biosynthesis pathway, from which 29 key candidate genes were obtained by WGCNA. Five UDP-Glycosyltransferases and four O-methyltransferases were suggested to be the candidate enzymes involved in synthetic pathway from gallic acid to bergenin by correlation analysis between transcriptional and metabolic levels and phylogenetic analysis. This study provides data resources and new insights for further studies on the biosynthesis of major active components in B. purpurascens.

Sex dimorphism and tissue specificity of gene expression changes in aging mice

BackgroundAging is a complex process that involves all tissues in an organism and shows sex dimorphism. While transcriptional changes in aging have been well characterized, the majority of studies have focused on a single sex and sex differences in gene expression in aging are poorly understood. In this study, we explore sex dimorphism in gene expression in aging mice across three tissues.MethodsWe collected gastrocnemius muscle, liver and white adipose tissue from young (6 months, n = 14) and old (24 months, n = 14) female and male C57BL/6NIA mice and performed RNA-seq. To investigate sex dimorphism in aging, we considered two levels of comparisons: (a) differentially expressed genes between females and males in the old age group and (b) comparisons between females and males across the aging process. We utilized differential expression analysis and gene feature selection to investigate candidate genes. Gene set enrichment analysis was performed to identify candidate molecular pathways. Furthermore, we performed a co-expression network analysis and chose the gene module(s) associated with aging independent of sex or tissue-type.ResultsWe identified both tissue-specific and tissue-independent genes associated with sex dimorphism in aged mice. Unique differentially expressed genes between old males and females across tissues were mainly enriched for pathways related to specific tissue function. We found similar results when exploring sex differences in the aging process, with the exception that in the liver genes enriched for lipid metabolism and digestive system were identified in both females and males. Combining enriched pathways across analyses, we identified amino acid metabolism, digestive system, and lipid metabolism as the core mechanisms of sex dimorphism in aging. Although the vast majority of age-related genes were sex and tissue specific, we identified 127 hub genes contributing to aging independent of sex and tissue that were enriched for the immune system and signal transduction.ConclusionsThere are clear sex differences in gene expression in aging across liver, muscle and white adipose. Core pathways, including amino acid metabolism, digestive system and lipid metabolism, contribute to sex differences in aging.

Genome-Wide Selection Sweep Analysis to Identify Candidate Genes with Black and Brown Color in Tibetan Sibu Yaks.

Although coat color is an important economic phenotype in domesticated yaks (Bos grunniens), its genetic basis is not yet fully understood. In this study, a genome-wide selective sweep and high-frequency runs of homozygosity (ROH) identification were performed on 50 yaks with different coat colors to investigate candidate genes (CDGs) related to coat color. The results suggested that 2263 CDGs were identified from the 5% interaction windows of the FST and θπ ratio, along with 2801 and 2834 CDGs from black and brown yaks with iHS, respectively. Furthermore, 648 and 691 CDGs from black and brown yaks, which were widely enriched in pathways related to melanogenesis, melanocyte differentiation, and melanosome organization via GO and KEGG functional enrichment, respectively, were confirmed on the basis of the intersection of three parameters. Additionally, the genome of brown yaks presented more ROH, longer ROH fragments, and higher inbreeding levels than those of black yaks. Specifically, a large number of genes related to melanin synthesis and regulation (e.g., UST, TCF25, and AHRR) from the ROH islands were confirmed to be under strong selection. In summary, the results of this study enhance the understanding of the genetic basis for determining yak coat color.

The Domestication of Wild Boar Could Result in a Relaxed Selection for Maintaining Olfactory Capacity.

Domesticated animals are artificially selected to exhibit desirable traits, however not all traits of domesticated animals are the result of deliberate selection. Loss of olfactory capacity in the domesticated pig (Sus scrofa domesticus) is one example. We used whole transcriptome analysis (RNA-Seq) to compare patterns of gene expression in the olfactory mucosa of the pig and two subspecies of wild boar (Sus scrofa), and investigate candidate genes that could be responsible for the loss of olfactory capacity. We identified hundreds of genes with reductions in transcript abundance in pig relative to wild boar as well as differences between the two subspecies of wild boar. These differences were detected mainly in genes involved in the formation and motility of villi, cilia and microtubules, functions associated with olfaction. In addition, differences were found in the abundances of transcripts of genes related to immune defenses, with the highest levels in continental wild boar subspecies. Overall, the loss of olfactory capacity in pigs appears to have been accompanied by reductions in the expression of candidate genes for olfaction. These changes could have resulted from unintentional selection for reduced olfactory capacity, relaxed selection for maintaining olfactory capacity, pleiotropic effects of genes under selection, or other non-selective processes. Our findings could be a cornerstone for future researches on wild boars, pigs, feral populations, and their evolutionary trajectories, aimed to provide tools to better calibrate species management as well as guidelines for breeders.

Exploring Candidate Gene Studies and Alexithymia: A Systematic Review.

Alexithymia is a trait involving difficulties in processing emotions. Genetic association studies have investigated candidate genes involved in alexithymia's pathogenesis. Therefore, the aim of the present study was to perform a systematic review of the genetic background associated with alexithymia. A systematic review of genetic studies of people with alexithymia was conducted. Electronic databases including PubMed, Scopus, and Web of Science were searched for the study purpose. We used the words "Alexithymia", "gene", "genetics", "variants", and "biomarkers". The present systematic review was performed following the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement. We found only candidate gene studies. A total of seventeen studies met the eligibility criteria, which comprised 22,361 individuals. The candidate genes associated with alexithymia were the serotoninergic pathway genes solute carrier family 6 member 4 (SLC6A4), serotonin 1A receptor (HTR1A), and serotonin 1A receptor (HTR2A); the neurotransmitter metabolism genes dopamine receptor D2 (DRD2), ankyrin repeat and kinase domain containing 1 (ANKK1), catechol-o-methyltransferase (COMT), brain-derived neurotrophic factor (BDNF), and oxytocin receptor (OXTR); and other pathway genes, vitamin D-binding protein (VDBP), tumor protein P53 regulated apoptosis inducing protein 1 (TP53AIP1), Rho GTPase Activating Protein 32 (ARHGAP32), and transmembrane protein 88B (TMEM88B). The results of this study showed that only case-control gene studies have been performed in alexithymia. On the basis of our findings, the majority of alexithymia genes and polymorphisms in this study belong to the serotoninergic pathway and neurotransmitter metabolism genes. These data suggest a role of serotoninergic neurotransmission in alexithymia. Nevertheless, more and future research is required to learn about the role of these genes in alexithymia.

Genetic analysis of yield components in buckwheat using high-throughput sequencing analysis and wild resource populations.

Fagopyrum tataricum, an important medicinal and edible crop, possesses significant agricultural and economic value. However, the development of buckwheat varieties and yields has been hindered by the delayed breeding progress despite the abundant material resources in China. Current research indicates that quantitative trait loci (QTLs) play a crucial role in controlling plant seed type and yield. To address these limitations, this study constructed recombinant inbred lines (RILs) utilizing both cultivated species and wild buckwheat as raw materials. In total, 84,521 Single Nucleotide Polymorphism (SNP) markers were identified through Genotyping-by-Sequencing (GBS) technology, and high-resolution and high-density SNP genetic maps were developed, which had significant value for QTL mapping, gene cloning and comparative mapping of buckwheat. In this study, we successfully identified 5 QTLs related to thousand grain weight (TGW), 9 for grain length (GL), and 1 for grain width (GW) by combining seed type and TGW data from 202 RIL populations in four different environments, within which one co-located QTL for TGW were discovered on the first chromosome. Transcriptome analysis during different grain development stages revealed 59 significant expression differences between the two materials, which can serve as candidate genes for further investigation into the regulation of grain weight and yield enhancement. The mapped major loci controlling TGW, GL and GW will be valuable for gene cloning and reveal the mechanism underlying grain development and marker-assisted selection in Tartary buckwheat.

EPEN-27. GAINING A CLUE FROM 1Q: A HIGH-RISK CHROMOSOMAL GAIN IN PEDIATRIC POSTERIOR FOSSA EPENDYMOMA

Abstract BACKGROUND Ependymomas are neuroepithelial tumours that can be classified into distinct molecular subgroups, each exhibiting a unique clinical outcome. Therapeutic efforts against the most aggressive and abundant subgroup of pediatric ependymoma (posterior fossa group A, PFA) have traditionally been hampered by a lack of known recurrent driver mutations. However, approximately 25% of PFA tumours exhibit gains of the chromosome arm 1q which is associated with an extremely poor prognosis despite aggressive treatment. By interrogating the multi-omic landscape of PFAs harbouring this copy number variation, we aimed to uncover genetic dependencies from which actionable therapeutics could be derived. METHODS Transcriptomic (bulk/single-cell RNA sequencing), proteomic (LC-MS/MS) and phosphoproteomic analyses were conducted on patient tissues and primary patient-derived cell lines to gain insight into the pathways that drive 1q gain pathogenesis. Chromatin immunoprecipitation sequencing of H3K27me3 and H3K27ac marked histones was carried out to profile the epigenetic landscape of these tumours, and whole genome CRISPR knockout screens were performed to reveal the contribution of essential genes unique to tumours harboring 1q gains. RESULTS Through the comparison of 1q gain and balanced PFA samples, our multi-omic analyses identified the up-regulation and essentiality of known glioma oncogenic drivers previously uncharacterized in PFA. The investigation of essential candidate genes showed a convergence on pathways related to ciliogenesis, with genetic vulnerabilities informing in vitro drug screening. Candidate genes were further validated by in vivo knockdown using established xenograft mouse models for pre-clinical testing. CONCLUSIONS This combined approach has allowed for the derivation of a functional cancer signature underlying 1q gains in PFA and presents novel therapeutic targets for this high-risk subgroup. PFA ependymoma is a deadly malignancy whose complex biology has so far eluded therapy, and new insights from this project will help to identify the first effective therapies for this vulnerable patient population.

Proteome Analysis Related to Unsaturated Fatty Acid Synthesis by Interfering with Bovine Adipocyte ACSL1 Gene.

Unsaturated fatty acids (UFAs) in beef play a vital role in promoting human health. Long-chain fatty acyl-CoA synthase 1 (ACSL1) is a crucial gene for UFA synthesis in bovine adipocytes. To investigate the protein expression profile during UFA synthesis, we performed a proteomic analysis of bovine adipocytes by RNA interference and non-interference with ACSL1 using label-free techniques. A total of 3558 proteins were identified in both the NC and si-treated groups, of which 1428 were differentially expressed proteins (DEPs; fold change ≥ 1.2 or ≤ 0.83 and p-value < 0.05). The enrichment analysis of the DEPs revealed signaling pathways related to UFA synthesis or metabolism, including cAMP, oxytocin, fatty acid degradation, glycerol metabolism, insulin, and the regulation of lipolysis in adipocytes (p-value < 0.05). Furthermore, based on the enrichment analysis of the DEPs, we screened 50 DEPs that potentially influence the synthesis of UFAs and constructed an interaction network. Moreover, by integrating our previously published transcriptome data, this study established a regulatory network involving differentially expressed long non-coding RNAs (DELs), highlighting 21 DEPs and 13 DELs as key genes involved in UFA synthesis. These findings present potential candidate genes for further investigation into the molecular mechanisms underlying UFA synthesis in bovines, thereby offering insights to enhance the quality of beef and contribute to consumer health in future studies.

Combined analysis of Polygonum cuspidatum transcriptome and metabolome revealed that PcMYB62, a transcription factor, responds to methyl jasmonate and inhibits resveratrol biosynthesis

A comparative transcriptomic and metabolomic analysis of Polygonum cuspidatum leaves treated with MeJA was carried out to investigate the regulatory mechanisms of its active compounds. A total of 692 metabolites and 77,198 unigenes were obtained, including 200 differentially accumulated metabolites and 6819 differentially expressed genes. We screened potential regulatory transcription factors involved in resveratrol and flavonoids biosynthesis, and successfully identified an MYB transcription factor, PcMYB62, which could significantly decrease the resveratrol content in P. cuspidatum leaves when over-expressed. PcMYB62 could directly bind to the MBS motifs in the promoter region of stilbene synthase (PcSTS) gene and repress its expression. Besides, PcMYB62 could also repress PcSTS expression and resveratrol biosynthesis in transgenic Arabidopsis thaliana. Our results provide abundant candidate genes for further investigation, and the new finding of the inhibitory role of PcMYB62 on the resveratrol biosynthesis could also potentially be used in metabolic engineering of resveratrol in P. cuspidatum.

Gene expression profiles of white bass (Morone chrysops) and hybrid striped bass (M. chrysops x M. saxatilis) gill tissue following Flavobacterium covae infection

Columnaris disease is a prevalent disease in freshwater environments caused by the ubiquitous aquatic pathogen Flavobacterium species. Adhesion to the external mucosal surfaces of fishes is the initial stage of infection, and the gills specifically have been identified as both a primary target and release site for this pathogen. Demonstrated here and in previous research, the hybrid striped bass (Morone chrysops x M. saxatilis), a prominent United States aquaculture product, is more susceptible to infection with F. covae than the maternal white bass (M. chrysops) parental species. To further elucidate the mechanisms underlying differences in resistance between these fish we examined gill gene expression profiles using RNA sequencing at different timepoints after F. covae infection. Patterns of differential gene expression and association with key enrichment terms indicate the effective immune response observed in white bass includes the up-regulation of multiple cytokines (IL-1β, IL-17C, TNF-α, G-CSF, IL-8, CCL16, CXCL9), hepcidins (HAMP and HAMP2), ribosomal subunit components (e.g., RPL13), and, interestingly, the down-regulation of leptin (LEPA) during initial (1 – 4 h) stages of infection. Conversely, up-regulation of the same genes was not detected in hybrid striped bass until 24 h after infection, indicating a delay in immune response mechanisms that is ultimately ineffective in protecting the host, as this was concurrent with the onset of mortality in these fish. Collectively, the presented results include several putative pathways and candidate genes for further investigation toward characterizing immune defense mechanisms underlying the resistance (white bass) and susceptibility (hybrid striped bass) for selective breeding efforts and/or biotechnological intervention.

Genetic insights into superior grain number traits: a QTL analysis of wheat-Agropyron cristatum derivative pubing3228

BackgroundAgropyron cristatum (L.) is a valuable genetic resource for expanding the genetic diversity of common wheat. Pubing3228, a novel wheat-A. cristatum hybrid germplasm, exhibits several desirable agricultural traits, including high grain number per spike (GNS). Understanding the genetic architecture of GNS in Pubing3228 is crucial for enhancing wheat yield. This study aims to analyze the specific genetic regions and alleles associated with high GNS in Pubing3228.MethodsThe study employed a recombination inbred line (RIL) population derived from a cross between Pubing3228 and Jing4839 to investigate the genetic regions and alleles linked to high GNS. Quantitative Trait Loci (QTL) analysis and candidate gene investigation were utilized to explore these traits.ResultsA total of 40 QTLs associated with GNS were identified across 16 chromosomes, accounting for 4.25–17.17% of the total phenotypic variation. Five QTLs (QGns.wa-1D, QGns.wa-5 A, QGns.wa-7Da.1, QGns.wa-7Da.2 and QGns.wa-7Da.3) accounter for over 10% of the phenotypic variation in at least two environments. Furthermore, 94.67% of the GNS QTL with positive effects originated from Pubing3228. Candidate gene analysis of stable QTLs identified 11 candidate genes for GNS, including a senescence-associated protein gene (TraesCS7D01G148000) linked to the most significant SNP (AX-108,748,734) on chromosome 7D, potentially involved in reallocating nutrients from senescing tissues to developing seeds.ConclusionThis study provides new insights into the genetic mechanisms underlying high GNS in Pubing3228, offering valuable resources for marker-assisted selection in wheat breeding to enhance yield.

Abstract 6148: Multiple new Ewing sarcoma susceptibility loci expand knowledge of germline genetic etiology and nominate mechanisms of risk

Abstract Ewing sarcoma (EwS) is a rare and aggressive pediatric cancer with peak incidence in the second decade of life. EwS occurs primarily in children of European ancestry suggesting a genetic component to susceptibility. Prior investigations identified six susceptibility loci associated with EwS, with evidence for additional signals not reaching the commonly accepted threshold for genome-wide significance (i.e., p&amp;lt;5×10−8). At least two of these loci demonstrate evidence of tagging variation in length of nearby GGAA microsatellites, which alter binding of the pathognomonic EWSR1::FLI1 fusion resulting in downstream dysregulation of target genes promoting sarcomagenesis. To identify additional susceptibility loci, we performed the largest genome-wide association study (GWAS) to date consisting of 1,640 EwS cases and 8,457 cancer-free individuals of European ancestry from 8 studies and matched by principal components. Genotype imputation was carried out by study/array using TOPMed data as the reference and each set was analyzed using PLINK 1.9 adjusting for significant principal components. Variants were included in each study if minor allele count was greater than five in each set of cases. Individual study results were combined using fixed effects meta-analysis in Metasoft with variants demonstrating evidence for heterogeneity excluded.For previously reported EwS loci (i.e., 1p36.22, 6p25.1, 10q21.3, 15q15.1, 20p11.22 and 20p11.23), odds ratios (OR) remained high for GWAS (OR=1.5-2.4) and the -log10 p-values grew by several orders of magnitude, providing strong evidence for replication in the additional 907 EwS cases and 7,111 cancer-free controls. Our analysis identified five novel loci reaching genome-wide significance (P-valuemeta&amp;lt; 5×10−8) at 5q32, 7q32.3, 8q24.2, 13q32.3, and 17q23.2. Risk allele frequency of newly identified loci ranged from 0.001 to 0.75with estimated ORs ranging from 1.31-4.30. eQTL analyses nominated nearby biologically plausible candidate genes for future functional investigation including LARS1, a gene implicated in osteosarcoma and skeletal muscle dysgenesis, at the 5q32 locus and COX5BP6, a gene implicated in age at menarche and testosterone levels, at 13q32.3.Our results add to evidence supporting a strong inherited genetic component to EwS risk and particularly a genetic architecture harboring a substantial number of common variants with moderate effect. Ongoing work is focusing on enrichment analyses of GGAA microsatellite repeat sequences in identified risk loci to search for evidence for germline-somatic interactions with EWSR1::FLI1. Citation Format: Aubrey K. Hubbard, Weiyin Zhou, Carrie Boyce, Javed Khan, Melissa M. Hudson, Kirsten K. Ness, Zhaoming Wang, Katherine A. Janeway, Philip J. Lupo, Lindsay M. Morton, Stephen J. Chanock, Thomas G. Grünewald, Olivier Delattre, Mitchell J. Machiela, Ewing Sarcoma Germline Genetics Group. Multiple new Ewing sarcoma susceptibility loci expand knowledge of germline genetic etiology and nominate mechanisms of risk [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 6148.

The Role of Genes and Genetic Variation in Human Tuberculosis Susceptibility: A Population Perspective

Tuberculosis (TB) is a serious infectious disease caused by Mycobacterium tuberculosis (Mtb) bacteria that affected many people around the world. However, not everyone who was exposed to Mtb got sick, which implied that some genetic factors influenced how people responded to TB infection. The question of whether TB was influenced more by genes or by the environment had been a topic of research for a long time. In this review paper, we examined the findings and difficulties of the studies on the genetic determinants of human TB susceptibility and how much genetic variation contributed to it, from twin and candidate gene studies to genome-wide association studies. This comprehensive review developed into the then-current state of knowledge and the intricate challenges inherent in researching the genetic underpinnings of human susceptibility to TB. The exploration of this genetic aspect spanned a spectrum, from classical twin studies and candidate gene investigations to more contemporary approaches like genome-wide association studies and genetic variation in noncoding RNA analysis.&#x0D; Within this evolving landscape, we highlighted the genes such as TNF, NRAMP, IFN-γ, NOS2, IGR, VDR, TYK2, TLR, MBL, IGRM, ASAP1, AGMO, FOXP1, P2X7, SP110, and UBLCP1 and the mechanisms involved in the development of TB. Furthermore, we explored the role of genetic variation in regulating the immune response to MTB infection collectively with environmental factors. Hence, we also reviewed how environmental factors, such as diet, living conditions, and co-infections, affected the likelihood and severity of TB. Understanding the interplay of genetic and environmental factors allowed us to identify the people who were most vulnerable to TB and design better strategies to prevent and treat it.

Linkage mapping and genomic prediction of grain quality traits in tropical maize (Zea mays L.).

The suboptimal productivity of maize systems in sub-Saharan Africa (SSA) is a pressing issue, with far-reaching implications for food security, nutrition, and livelihood sustainability within the affected smallholder farming communities. Dissecting the genetic basis of grain protein, starch and oil content can increase our understanding of the governing genetic systems, improve the efficacy of future breeding schemes and optimize the end-use quality of tropical maize. Here, four bi-parental maize populations were evaluated in field trials in Kenya and genotyped with mid-density single nucleotide polymorphism (SNP) markers. Genotypic (G), environmental (E) and G×E variations were found to be significant for all grain quality traits. Broad sense heritabilities exhibited substantial variation (0.18-0.68). Linkage mapping identified multiple quantitative trait loci (QTLs) for the studied grain quality traits: 13, 7, 33, 8 and 2 QTLs for oil content, protein content, starch content, grain texture and kernel weight, respectively. The co-localization of QTLs identified in our research suggests the presence of shared genetic factors or pleiotropic effects, implying that specific genomic regions influence the expression of multiple grain quality traits simultaneously. Genomic prediction accuracies were moderate to high for the studied traits. Our findings highlight the polygenic nature of grain quality traits and demonstrate the potential of genomic selection to enhance genetic gains in maize breeding. Furthermore, the identified genomic regions and single nucleotide polymorphism markers can serve as the groundwork for investigating candidate genes that regulate grain quality traits in tropical maize. This, in turn, can facilitate the implementation of marker-assisted selection (MAS) in breeding programs focused on improving grain nutrient levels.

Molecular Investigation and Preliminary Validation of Candidate Genes Associated with Neurological Damage in Heat Stroke.

Heat stroke (HS) is a severe medical condition characterized by a systemic inflammatory response that may precipitate multi-organ dysfunction, with a particular predilection for inducing profound central nervous system impairments. We aim to employ bioinformatics techniques for the retrieval and analysis of genes associated with heat stroke-induced neurological damage. We performed a comprehensive analysis of the GSE64778 dataset from the Sequence Read Archive, resulting in the identification of 1178 significantly differentially expressed genes (DEGs). We retrieved 2914 genes associated with heat stroke from the GeneCards database and 2377 genes associated with heat stroke from the Comparative Toxicogenomics Database (CTD). The intersection of the top 300 DEGs in the GSE64778 dataset intersected with the search results of GeneCards and CTD, yielding 25 final candidates for DEGs associated with heat stroke. Gene Ontology functional annotation results indicated that the target genes were mainly involved in apoptosis, stress response, and negative regulation of cellular processes and function in processes such as protein dimerization and protein binding. The Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed a predominant enrichment of candidate target genes within the PI3K-AKT signaling pathway. Subsequent protein-protein interaction network analysis highlighted HSP90aa1 as a central gene, indicating its pivotal role by possessing the highest number of edges among the genes enriched in the PI3K-AKT signaling pathway. Quantitative reverse transcription-polymerase chain reaction analysis performed on blood samples from patients validated the expression of Hsp90aa1 in individuals exhibiting early neurological damage in HS, consistent with the findings from the mRNA bioinformatics analysis. Additionally, the bioinformatics analysis of the upstream microRNAs (miRNAs) regulating HSP90aa1 and the target miRNAs associated with candidate long non-coding RNAs (lncRNAs) identified three lncRNAs, eight miRNAs, and one mRNA in the regulatory network. The DIANA Tools database and algorithms were employed for pathway enrichment and correlation analysis, revealing a significant association between LOC102547734 and MIR-206-3p, with the latter being identified as a target binding site Moreover, the analysis unveiled a correlation between MIR-206-3p and HSP90aa1, implicating the latter as a potential target binding site within the regulatory network.

OsCSD2 and OsCSD3 Enhance Seed Storability by Modulating Antioxidant Enzymes and Abscisic Acid in Rice.

Seed deterioration during storage poses a significant challenge to rice production, leading to a drastic decline in both edible quality and viability, thereby impacting overall crop yield. This study aimed to address this issue by further investigating candidate genes associated with two previously identified QTLs for seed storability through genome association analysis. Among the screened genes, two superoxide dismutase (SOD) genes, OsCSD2 (Copper/zinc Superoxide Dismutase 2) and OsCSD3, were selected for further study. The generation of overexpression and CRISPR/Cas9 mutant transgenic lines revealed that OsCSD2 and OsCSD3 play a positive regulatory role in enhancing rice seed storability. Subsequent exploration of the physiological mechanisms demonstrated that overexpression lines exhibited lower relative electrical conductivity, indicative of reduced cell membrane damage, while knockout lines displayed the opposite trend. Furthermore, the overexpression lines of OsCSD2 and OsCSD3 showed significant increases not only in SOD but also in CAT and POD activities, highlighting an augmented antioxidant system in the transgenic seeds. Additionally, hormone profiling indicated that ABA contributed to the improved seed storability observed in these lines. In summary, these findings provide valuable insights into the regulatory mechanisms of OsCSDs in rice storability, with potential applications for mitigating grain loss and enhancing global food security.

Transcriptome identification of differential mammary genes of Kazakh horses during early pregnancy

Kazakh mares have attracted widespread attention with their outstanding lactation traits. Lactation is a complex dynamic process regulated by multiple factors. The extensive application of transcriptome sequencing technology enables researchers to further explore this biological issue. This study selected three pregnant and three non-pregnant Kazakh mares as the research subject. Their mammary glands were taken for transcriptome sequencing. The results show that there are 9 lncRNAs and 122 mRNAs differentially expressed between the two groups. GO enrichment analysis shows that there are 175 molecular functions, 59 cellular components, and 555 biological processes, including cellular hormone metabolic process, hormone catabolic process, and I-kappaB kinase/NF-kappaB signaling. KEGG enrichment analysis exhibits that these differential genes are mainly enriched in the NF-kappa B signaling pathway, steroid hormone biosynthesis, breast cancer, ECM-receptor interaction, and MAPK signaling pathway. WNT4, DPP4, and NFKBIA are key nodes regulating breast activation. Conclusions: Through the comparative analysis of the transcriptome data of mammary tissues of pregnant and non-pregnant mares, relevant differentially expressed genes are screened and analyzed. This study provides valuable fundamental data for investigating candidate genes related to the lactation regulation and mammogenesis of Kazakh horses.

Conditionally mutant animal model for investigating the invasive trophoblast cell lineage.

Placental development involves coordinated expansion and differentiation of trophoblast cell lineages possessing specialized functions. Among the differentiated trophoblast cell lineages are invasive trophoblast cells, which exit the placenta and invade the uterus, where they restructure the uterine parenchyma and facilitate remodeling of uterine spiral arteries. The rat exhibits deep intrauterine trophoblast cell invasion, a feature shared with human placentation, and is also amenable to gene manipulation using genome-editing techniques. In this investigation, we generated a conditional rat model targeting the invasive trophoblast cell lineage. Prolactin family 7, subfamily b, member 1 (Prl7b1) is uniquely and abundantly expressed in the rat invasive trophoblast cell lineage. Disruption of Prl7b1 did not adversely affect placental development. We demonstrated that the Prl7b1 locus could be effectively used to drive the expression of Cre recombinase in invasive trophoblast cells. Our rat model represents a new tool for investigating candidate genes contributing to the regulation of invasive trophoblast cells and their roles in trophoblast-guided uterine spiral artery remodeling.