Single Gene Research Articles

Identification and Fine Mapping of a Mutant pv‐nts Gene Responsible for Dwarf and Thin Stem of Snap Bean (Phaseolus vulgaris L.)

ABSTRACTPlant height is one of the most important traits in the breeding of snap bean, which determines the planting density and the resistance to failure, which in turn affects its yield and quality. Therefore, studying the molecular mechanism of plant height in snap bean is an important measure to realize the improvement of snap bean. We obtained a dwarf, thin‐stemmed mutant nts (normal to slim) from a dwarf variety of snap bean A18 via 60CO‐γ‐ray treatment. We conducted phenotypic observations, endogenous hormone content measurements and genetic analyses of the dwarfing thin‐stemmed mutant nts and explored gene localization and candidate gene screening for the mutant trait in snap bean. Compared with wild‐type A18, nts mutant exhibited various abnormal phenotypes such as dwarfing, reduced branching, thinner top stem, reduced plant width, reduced number of leaf area and thousand grain weight and increased content of hormones such as indole‐3‐acetic acid (IAA) in the top stem. Genetic analysis indicated that the mutant trait was controlled by a single recessive nuclear gene, and the mutant gene was named pv‐nts. pv‐nts was localized to a 361.1‐kb segment on chromosome 8 as revealed by bovine serum albumin (BSA) hybrid pool sequencing and simple sequence repeat (SSR) molecular markers. Phvul.008G106300 (encoding LAX2 protein) was identified as a candidate gene corresponding to pv‐nts via gene function annotation. Phvul.008G106300 was significantly upregulated in nts mutant compared with wild‐type A18, which was consistent with the results of endogenous IAA levels. Sequence analysis showed that the Phvul.008G106300 gene in nts had a base mutation that altered the protein structure, thus causing the dwarfed, thin‐stemmed phenotype of cauliflower. Taken together, these results contribute to a better understanding of the genetic basis of dwarfing traits in snap bean.

Identifying cooperating cancer driver genes in individual patients through hypergraph random walk

ObjectiveIdentifying cancer driver genes, especially rare or patient-specific cancer driver genes, is a primary goal in cancer therapy. Although researchers have proposed some methods to tackle this problem, these methods mostly identify cancer driver genes at single gene level, overlooking the cooperative relationship among cancer driver genes. Identifying cooperating cancer driver genes in individual patients is pivotal for understanding cancer etiology and advancing the development of personalized therapies. MethodsHere, we propose a novel Personalized Cooperating cancer Driver Genes (PCoDG) method by using hypergraph random walk to identify the cancer driver genes that cooperatively drive individual patient cancer progression. By leveraging the powerful ability of hypergraph in representing multi-way relationships, PCoDG first employs the personalized hypergraph to depict the complex interactions among mutated genes and differentially expressed genes of an individual patient. Then, a hypergraph random walk algorithm based on hyperedge similarity is utilized to calculate the importance scores of mutated genes, integrating these scores with signaling pathway data to identify the cooperating cancer driver genes in individual patients. ResultsThe experimental results on three TCGA cancer datasets (i.e., BRCA, LUAD, and COADREAD) demonstrate the effectiveness of PCoDG in identifying personalized cooperating cancer driver genes. These genes identified by PCoDG not only offer valuable insights into patient stratification correlating with clinical outcomes, but also provide an useful reference resource for tailoring personalized treatments. ConclusionWe propose a novel method that can effectively identify cooperating cancer driver genes for individual patients, thereby deepening our understanding of the cooperative relationship among personalized cancer driver genes and advancing the development of precision oncology.

Compensatory mutations potentiate constructive neutral evolution by gene duplication.

The functions of proteins generally depend on their assembly into complexes. During evolution, some complexes have transitioned from homomers encoded by a single gene to heteromers encoded by duplicate genes. This transition could occur without adaptive evolution through intermolecular compensatory mutations. Here, we experimentally duplicated and evolved a homodimeric enzyme to determine whether and how this could happen. We identified hundreds of deleterious mutations that inactivate individual homodimers but produce functional enzymes when coexpressed as duplicated proteins that heterodimerize. The structure of one such heteromer reveals how both losses of function are buffered through the introduction of asymmetry in the complex that allows them to subfunctionalize. Constructive neutral evolution can thus occur by gene duplication followed by only one deleterious mutation per duplicate.

Host and venom evolution in parasitoid wasps: does independently adapting to the same host shape the evolution of the venom gland transcriptome?

BackgroundVenoms have repeatedly evolved over 100 occasions throughout the animal tree of life, making them excellent systems for exploring convergent evolutionary novelty. Growing evidence supports that venom evolution is predominantly driven by prey or host-related selection pressures, and the expression patterns of venom glands reflect adaptive evolution. However, it remains elusive whether the evolution of expression patterns in venom glands is likewise a convergent evolution driven by their prey/host species.ResultsWe utilized parasitoid wasps that had independently adapted to Drosophila hosts as models to investigate the convergent evolution of venom gland transcriptomes in 19 hymenopteran species spanning ~ 200 million years of evolution. Comparative transcriptome analysis reveals that the global expression patterns among the venom glands of Drosophila parasitoid wasps do not achieve higher similarity compared to non-Drosophila parasitoid wasps. Further evolutionary analyses of expression patterns at the single gene, orthogroup, and Gene Ontology (GO) term levels indicate that some orthogroups/GO terms show correlation with the Drosophila parasitoid wasps. However, these groups rarely include genes highly expressed in venom glands or putative venom genes in the Drosophila parasitoid wasps.ConclusionsOur study suggests that convergent evolution may not play a predominant force shaping gene expression levels in the venom gland of the Drosophila parasitoid wasps, offering novel insights into the co-evolution between venom and prey/host.

Identification of HTRA1, DPT and MXRA5 as potential biomarkers associated with osteoarthritis progression and immune infiltration

BackgroundOur study aimed to identify potential specific biomarkers for osteoarthritis (OA) and assess their relationship with immune infiltration.MethodsWe utilized data from GSE117999, GSE51588, and GSE57218 as training sets, while GSE114007 served as a validation set, all obtained from the GEO database. First, weighted gene co-expression network analysis (WGCNA) and functional enrichment analysis were performed to identify hub modules and potential functions of genes. We subsequently screened for potential OA biomarkers within the differentially expressed genes (DEGs) of the hub module using machine learning methods. The diagnostic accuracy of the candidate genes was validated. Additionally, single gene analysis and ssGSEA was performed. Then, we explored the relationship between biomarkers and immune cells. Lastly, we employed RT-PCR to validate our results.ResultsWGCNA results suggested that the blue module was the most associated with OA and was functionally associated with extracellular matrix (ECM)-related terms. Our analysis identified ALB, HTRA1, DPT, MXRA5, CILP, MPO, and PLAT as potential biomarkers. Notably, HTRA1, DPT, and MXRA5 consistently exhibited increased expression in OA across both training and validation cohorts, demonstrating robust diagnostic potential. The ssGSEA results revealed that abnormal infiltration of DCs, NK cells, Tfh, Th2, and Treg cells might contribute to OA progression. HTRA1, DPT, and MXRA5 showed significant correlation with immune cell infiltration. The RT-PCR results also confirmed these findings.ConclusionsHTRA1, DPT, and MXRA5 are promising biomarkers for OA. Their overexpression strongly correlates with OA progression and immune cell infiltration.

Immunogenic cell death (ICD) genes predict immunotherapy response and therapeutic targets in acute myeloid leukemia (AML).

Numerous studies have demonstrated acute myeloid leukemia (AML) is one of the malignancies with high mortality worldwide. Immunogenic cell death (ICD) is a form of cell death that is specialised in that it triggers the body's immune response, particularly the adaptive immune response. Recent evidence has confirmed that pseudogenes are implicated in multiple human tumorigenesis and progression although lacking the function of coding protein. However, the roles of ICD-associated genes in AML remain largely unascertained. TCGA-AML and GSE71014 cohorts were picked out and we combined them into a merged dataset by removing the batch effect using the sva package in the R project. A consensus clustering analysis of the ICD genes in AML was performed to define subgroups. Based on the expression of 15 prognostic-related pseudogenes, we developed a prognostic model and categorized AML samples into low and high-risk groups. AML was differentiated into two subgroups (C1 and C2 clusters). Most ICD-related genes were significantly up-regulated in the C2 cluster. The single sample gene set enrichment analysis (ssGSEA) revealed that the immune cell infiltration and immune checkpoint gene expression of the C2 cluster was strongly high, suggesting that the C2 population responded well to immune checkpoint blockade (ICB) therapy and had better survival. The C1 group was sensitive to chemotherapy, including Cytarabine, Midostaurin, and Doxorubicin. On the other hand, 15 ICD-related pseudogenes were identified to be associated with AML prognosis. The receiver operator curve (ROC) analysis and nomogram manifested that our prognostic model had high accuracy in predicting survival. However, the high-risk group was sensitive to ICB therapy and chemotherapy such as Methotrexate, Cytarabine, and Axitinib while the low-risk group benefited from 5-Fluorouracil, Talazoparib, and Navitoclax therapy. In summary, we defined two subgroups relying on 33 ICD-related genes and this classification exerted a decisive role in assessing immunotherapy and chemotherapy benefit. Significantly, a prognostic signature identified by critical ICD-related pseudogene was created. The pseudogene prognostic signature had a powerful performance in predicting prognosis and therapeutic efficacy, including immunotherapy and chemotherapy to AML. Our research points out novel implications of ICD in cancer prognosis and treatment approach choice.

Triple gene mutations boost amylose and resistant starch content in rice: insights from sbe2b/sbe1/OE-Wxa mutants.

Previous studies have modified rice's resistant starch (RS) content by mutating single and double genes. These mutations include knocking out or reducing the expression of sbe1 or sbe2b genes, as well as overexpressing Wxa . However, the impact of triple mutant sbe2b/sbe1/OE-Wxa on RS contents remained unknown. Here, we constructed a double mutant with sbe2b/RNAi-sbe1, based on IR36ae with sbe2b, and a triple mutant with sbe2b/RNAi-sbe1/OE-Wxa , based on the double mutant. The results showed that the amylose and RS contents gradually increased with an increase in the number of mutated genes. The triple mutant exhibited the highest amylose and RS contents, with 41.92% and 4.63%, respectively, which were 2- and 5-fold higher than those of the wild type, which had 22.19% and 0.86%, respectively. All three mutants altered chain length and starch composition compared to the wild type. However, there was minimal difference observed among the mutants. The Wxa gene contributed to the improvement of 1000-grain weight and seed-setting rate, in addition to the highest amylose and RS contents. Thus, our study offers valuable insight for breeding rice cultivars with a higher RS content and yields.

Identification and Validation of Aging- and Endoplasmic Reticulum Stress-Related Genes in Periodontitis Using a Competing Endogenous RNA Network.

Periodontitis is a multifactorial chronic inflammatory disease that destroy periodontium. Apart from microbial infection and host immune responses, emerging evidence shows aging and endoplasmic reticulum stress (ER stress) play a key role in periodontitis pathogenesis. The aim of this study is to identify aging-related genes (ARGs) and endoplasmic reticulum stress-related genes (ERGs) in periodontitis. Data were obtained from the Gene Expression Omnibus (GEO), Human Ageing Genomic Resources (HAGR) and GeneCards databases to identify differentially expressed mRNAs/miRNAs/lncRNAs (DEmRNAs/DEmiRNAs/DElncRNAs), ARGs and ERGs, respectively. We used the MultiMiR database for the reverse prediction of miRNAs and predicted miRNA-lncRNA interactions using the STARBase database. Afterwards, we constructed a mRNA-miRNA-lncRNA ceRNA network. A total of 10 hub genes, namely LCK, LYN, CXCL8, IL6, HCK, IL1B, BTK, CXCL12, GNAI1 and FCER1G, and 5 DEmRNAs-ARGs-ERGs were then discovered. Further, weighted gene co-expression network analysis (WGCNA) and single sample gene set enrichment analysis (ssGSEA) were performed to explore co-expression modules and immune infiltration respectively. Finally, we used transmission electron microscope (TEM), inverted fluorescence microscopy, quantitative real-time polymerase chain reaction (qRT-PCR) and Western Blot to verify the bioinformatic results in periodontal ligament stem cells (PDLSCs) infected with Porphyromonas gingivalis (P. gingivalis). The experimental results broadly confirmed the accuracy of bioinformatic analysis. The present study established an aging- and ER stress-related ceRNA network in periodontitis, contributing to a deeper understanding of the pathogenesis of periodontitis.

Single cell RNA-sequencing identifies the effect of Normothermic ex vivo liver perfusion on liver-resident T cells

BackgroundNormothermic ex vivo liver perfusion (NEVLP) is an exciting strategy to preserve livers prior to transplant, however, the effects of NEVLP on the phenotype of tissue-resident immune cells is largely unknown. The presence of tissue-resident memory T cells (TRM) in the liver may protect against acute rejection and decrease allograft dysfunction. Therefore, we investigated the effects of NEVLP on liver TRMs and assessed the ability of anti-inflammatory cytokines to reduce TRM activation during NEVLP. MethodsRat livers underwent NEVLP with or without the addition of IL-10 and TGF-β. Naïve and cold storage livers served as controls. Following preservation, TRM T cell gene expression profiles were assessed through single cell RNA sequencing (scRNA-seq). Differential gene expression analysis was performed with Wilcoxon rank sum test to identify differentially expressed genes (DEGs) associated with a specific treatment group. Using the online Database for Annotation, Visualization and Integrated Discovery (DAVID), gene set enrichment was then conducted with Fisher's exact test on DEGs to highlight differentially regulated pathways and functional terms associated with treatment groups. ResultsThrough scRNA-seq analysis, an atlas of liver-resident memory T cell subsets was created for all livers. TRM T cells could be identified in all livers, and through scRNA-seq, DEG was identified with Wilcoxon rank sum test at FDR < 0.05. Based on the gene set enrichment analysis of DEGs using Fisher's exact test, NEVLP is associated with downregulation of multiple gene enrichment pathways associated with surface proteins. Furthermore, NEVLP with anti-inflammatory cytokines was associated with down regulation of 52 genes in TRM T cells when compared to NEVLP alone (FDR <0.05), most of which are pro-inflammatory. ConclusionThis is the first study to create an atlas of liver TRM T cells in the rat liver undergoing NEVLP and demonstrate the effects of NEVLP on liver TRM T cells at the single cell gene expression level.

MODY Only Monogenic? A Narrative Review of the Novel Rare and Low-Penetrant Variants.

Maturity-onset diabetes of the young (MODY) represents the most frequent form of monogenic diabetes mellitus (DM), currently classified in 14 distinct subtypes according to single gene mutations involved in the differentiation and function of pancreatic β-cells. A significant proportion of MODY has unknown etiology, suggesting that the genetic landscape is still to be explored. Recently, novel potentially MODY-causal genes, involved in the differentiation and function of β-cells, have been identified, such as RFX6, NKX2.2, NKX6.1, WFS1, PCBD1, MTOR, TBC1D4, CACNA1E, MNX1, AKT2, NEUROG3, EIF2AK3, GLIS3, HADH, and PTF1A. Genetic and clinical features of MODY variants remain highly heterogeneous, with no direct genotype-phenotype correlation, especially in the low-penetrant subtypes. This is a narrative review of the literature aimed at describing the current state-of-the-art of the novel likely MODY-associated variants. For a deeper understanding of MODY complexity, we also report some related controversies concerning the etiological role of some of the well-known pathological genes and MODY inheritance pattern, as well as the rare association of MODY with autoimmune diabetes. Due to the limited data available, the assessment of MODY-related genes pathogenicity remains challenging, especially in the setting of rare and low-penetrant subtypes. In consideration of the crucial importance of an accurate diagnosis, prognosis and management of MODY, more studies are warranted to further investigate its genetic landscape and the genotype-phenotype correlation, as well as the pathogenetic contribution of the nongenetic modifiers in this cohort of patients.

Metabolism of 2,4-D in plants: comparative analysis of metabolic detoxification pathways in tolerant crops and resistant weeds.

The commercialization of 2,4-D (2,4-dichlorophenoxyacetic acid) latifolicide in 1945 marked the beginning of the selective herbicide market, with this active ingredient playing a pivotal role among commercial herbicides due to the natural tolerance of monocots compared with dicots. Due to its intricate mode of action, involving interactions within endogenous auxin signaling networks, 2,4-D was initially considered a low-risk herbicide to evolve weed resistance. However, the intensification of 2,4-D use has contributed to the emergence of 2,4-D-resistant broadleaf weeds, challenging earlier beliefs. This review explores 2,4-D tolerance in crops and evolved resistance in weeds, emphasizing an in-depth understanding of 2,4-D metabolic detoxification. Nine confirmed 2,4-D-resistant weed species, driven by rapid metabolism, highlight cytochrome P450 monooxygenases in Phase I and glycosyltransferases in Phase II as key enzymes. Resistance to 2,4-D may also involve impaired translocation associated with mutations in auxin/indole-3-acetic acid (Aux/IAA) co-receptor genes. Moreover, temperature variations affect 2,4-D efficacy, with high temperatures increasing herbicide metabolism rates and reducing weed control, while drought stress did not affect 2,4-D efficacy. Research on 2,4-D resistance has primarily focused on non-target-site resistance (NTSR) mechanisms, including 2,4-D metabolic detoxification, with limited exploration of the inheritance and genetic basis underlying these traits. Resistance to 2,4-D in weeds is typically governed by a single gene, either dominant or incompletely dominant, raising questions about gain-of-function or loss-of-function mutations that confer resistance. Future research should unravel the physiological and molecular-genetic basis of 2,4-D NTSR, exploring potential cross-resistance patterns and assessing fitness costs that may affect future evolution of auxin-resistant weeds. © 2024 Society of Chemical Industry.

Genomic and functional determinants of host spectrum in Group B Streptococcus.

Group B Streptococcus (GBS) is a major human and animal pathogen that threatens public health and food security. Spill-over and spill-back between host species is possible due to adaptation and amplification of GBS in new niches but the evolutionary and functional mechanisms underpinning those phenomena are poorly known. Based on analysis of 1,254 curated genomes from all major GBS host species and six continents, we found that the global GBS population comprises host-generalist, host-adapted and host-restricted sublineages, which are found across host groups, preferentially within one host group, or exclusively within one host group, respectively, and show distinct levels of recombination. Strikingly, the association of GBS genomes with the three major host groups (humans, cattle, fish) is driven by a single accessory gene cluster per host, regardless of sublineage or the breadth of host spectrum. Moreover, those gene clusters are shared with other streptococcal species occupying the same niche and are functionally relevant for host tropism. Our findings demonstrate (1) the heterogeneity of genome plasticity within a bacterial species of public health importance, enabling the identification of high-risk clones; (2) the contribution of inter-species gene transmission to the evolution of GBS; and (3) the importance of considering the role of animal hosts, and the accessory gene pool associated with their microbiota, in the evolution of multi-host bacterial pathogens. Collectively, these phenomena may explain the adaptation and clonal expansion of GBS in animal reservoirs and the risk of spill-over and spill-back between animals and humans.

Overlapping hearing and communication profiles for the deletion and the RAI1 variant form of Smith-Magenis Syndrome (SMS)

Smith-Magenis syndrome (SMS), a rare, genetically linked complex developmental disorder is associated with hearing loss and delays in speech-language development. Approximately 70 % of those with SMS have a genetic deletion within chromosome 17p11.2 and 10 % have a single gene mutation in the same area, known as the RAI1 variant form of SMS. Previous studies presented preliminary comparisons of the phenotype of those with deletion versus the mutation form of SMS, but none focused on hearing, speech-language, and communication profiles. The current study examined patient registry data and compared two groups of individuals with SMS to determine if genetic differences influence the communication phenotype and to determine the importance of the RAI1 gene in hearing, speech, and language abilities in children. Speech-language and hearing data from the international SMS Patient Registry for 33 subjects with SMS were analyzed: 23 with a genetic deletion (SMS (del)) and 10 with an RAI1 mutation (SMS (RAI1)). Hearing status, otopathology findings, early speech-language milestones, mode of communication, intelligibility, vocal quality, language abilities, and literacy skills were analyzed. There were small differences between the groups for hearing status, otopathological findings, mode of communication, voice quality, intelligibility, speech-language abilities, and literacy. Overlap in the speech-language phenotype between groups confirms previous hypotheses that suggest haploinsufficiency of the RAI1 gene is responsible for the SMS phenotype and that the RAI1 gene is critical for speech-language development. Future studies should include direct testing of receptive and expressive language abilities, including analyses of language samples, with larger groups of individuals to replicate and extend the current findings.

The Mitochondrial Genome of Ylistrum japonicum (Bivalvia, Pectinidae) and Its Phylogenetic Analysis.

The Ylistrum japonicum is a commercially valuable scallop known for its long-distance swimming abilities. Despite its economic importance, genetic and genomic research on this species is limited. This study presents the first complete mitochondrial genome of Y. japonicum. The mitochondrial genome is 19,475 bp long and encompasses 13 protein-coding genes, three ribosomal RNA genes, and 23 transfer RNA genes. Two distinct phylogenetic analyses were used to explore the phylogenetic position of the Y. japonicum within the family Pectinidae. Based on one mitochondrial phylogenetic analysis by selecting 15 Pectinidae species and additional outgroup taxa and one single gene phylogenetic analysis by 16S rRNA, two phylogenetic trees were constructed to provide clearer insights into the evolutionary placement of Y. japonicum within the family Pectinidae. Our analysis reveals that Ylistrum is a basal lineage to the Pectininae clade, distinct from its previously assigned tribe, Amusiini. This study offers critical insights into the genetic makeup and evolutionary history of Y. japonicum, enhancing our knowledge of this economically vital species.

Associations between historical and contemporary measures of structural racism and leukocyte telomere length: The Multi-Ethnic Study of Atherosclerosis (MESA)

BackgroundWe assessed the link between two manifestations of structural racism—historical redlining and contemporary racial residential segregation—and baseline and 10-year changes in leukocyte telomere length (LTL). MethodsWe used data on Black and Hispanic/Latinx participants from Exams I and V of the Multi-Ethnic Study of Atherosclerosis Stress Ancillary Study (N = 741, age range = 45–84 years). LTL was defined as the ratio of telomeric DNA to a single copy gene (T/S), and 10-year changes were adjusted for regression to the mean. We used 1930s Home Owners' Loan Corporation maps to assign three historical redlining grades (A&B: best/still desirable, C: declining, D: hazardous/redlined) to participants’ neighborhoods (census-tracts) at baseline. The Getis-Ord Gi∗ statistic was used to evaluate census-tract level baseline residential segregation (low/moderate/high). ResultsIn mixed-effects regression models accounting for neighborhood clustering, individual characteristics, and current neighborhood environments, those living in highly segregated Black neighborhoods had 0.08 shorter baseline LTL (95% CI: −0.13, −0.04), than those residing in the least segregated neighborhoods. We did not find a relationship between residing in segregated neighborhoods and 10-year LTL changes, and associations between residing in historically redlined neighborhoods and both baseline LTL and 10-year changes in LTL were null. Across discriminatory disinvestment trajectories examined, individuals residing in highly segregated but non-redlined neighborhoods had 0.6 shorter baseline LTL than individuals residing in non-redlined neighborhoods with low/moderate segregation (95% CI: −0.12, −0.01). ConclusionsOur results highlight the impact of racial segregation on cellular aging and underscore the need to ameliorate structural inequities within segregated neighborhoods.

How exome sequencing improves the diagnostics and management of men with non-syndromic infertility.

Male infertility affects approximately 17% of all men and represents a complex disorder in which not only semen parameters such as sperm motility, morphology, and number of sperm are highly variable, but also testicular phenotypes range from normal spermatogenesis to complete absence of germ cells. Genetic factors significantly contribute to the disease but chromosomal aberrations, mostly Klinefelter syndrome, and microdeletions of the Y-chromosome have remained the only diagnostically and clinically considered genetic causes. Monogenic causes remain understudied and, thus, often unidentified, leaving the majority of the male factor couple infertility pathomechanistically unexplained. This has been changing mostly because of the introduction of exome sequencing that allows the analysis of multiple genes in large patient cohorts. As a result, pathogenic variants in single genes have been associated with non-syndromic forms of all aetiologic sub-categories in the last decade. This review highlights the contribution of exome sequencing to the identification of novel disease genes for isolated (non-syndromic) male infertility by presenting the results of a comprehensive literature search. Both, reduced sperm count in azoospermic and oligozoospermic patients, and impaired sperm motility and/or morphology, in asthenozoospermic and/or teratozoospermic patients are highly heterogeneous diseases with well over 100 different candidate genes described for each entity. Applying the standardized evaluation criteria of the ClinGen gene curation working group, 70 genes with at least moderate evidence to contribute to the disease are highlighted. The implementation of these valid disease genes in clinical exome sequencing is important to increase the diagnostic yield in male infertility and, thus, improve clinical decision-making and appropriate genetic counseling. Future advances in androgenetics will continue to depend on large-scale exome and genome sequencing studies of comprehensive international patient cohorts, which are the most promising approaches to identify additional disease genes and provide reliable data on the gene-disease relationship.

A large-scale in vivo screen to investigate the roles of human genes in Drosophila melanogaster.

Understanding the signaling pathways in which genes participate is essential for discovering the etiology of diseases in humans. The model organism, Drosophila melanogaster, has been crucial in understanding the signaling pathways in humans, given the evolutionary conservation of a significant number of genes between the two species. Genetic screens using Drosophila are a useful way of testing large number of genes to study their function and roles within signaling pathways. We conducted a large-scale genetic screen to identify which human genes cause an alteration in the morphology of the Drosophila eye. The GMR-Gal4 was employed to activate a single UAS-human gene in the eye tissue. In total, we screened 802 UAS-human gene stocks, corresponding to 787 human protein-coding genes, for the ability to influence eye development. We found that overexpression of 64 human genes were capable of disrupting eye development, as determined by phenotypic changes in eye texture, size, shape, bristle morphology, and ommatidia organization. Subsequent analysis revealed that the fly genome encodes proteins that are homologous to a majority of the 64 human genes, raising the possibility that overexpression of these transgenes altered eye development by altering the activity of evolutionarily conserved developmental signaling pathways. Consistent with this hypothesis, a secondary screen demonstrated that overexpression of fly homologs produced phenotypes that mimicked those produced by overexpression of the human gene. Our screening has identified 64 human genes capable of inducing phenotypes in the fly, offering a foundation for ongoing research aimed at understanding functionally conserved pathways across species.

Non-Thermal Effects of Terahertz Radiation on Gene Expression: Systematic Review and Meta-Analysis.

With the advancement of terahertz technology, unveiling the mysteries of terahertz has had a profound impact on the field of biomedicine. However, the lack of systematic comparisons for gene expression signatures may diminish the effectiveness and efficiency of identifying common mechanisms underlying terahertz effects across diverse research findings. We performed a comprehensive review and meta-analysis to compile patterns of gene expression profiles associated with THz radiation. Thorough bibliographic reviews were conducted, utilizing the PubMed, Embase, Web of Science, and ProQuest databases to extract references from published articles. Raw CEL files were obtained from Gene Expression Omnibus and preprocessed using Bioconductor packages. This systematic review (Registration No. CDR42024502937) resulted in a detailed analysis of 13 studies (14 papers). There are several possible mechanisms and pathways through which THz radiation could cause biological changes. While the established gene expression results are largely associated with immune response and inflammatory markers, other genes demonstrated transcriptional outcomes that may unravel unknown functions. The enrichment of genes primarily found networks associated with broader stress responses. Altogether, the findings showed that THz can induce a distinct transcriptomic profile that is not associated with a microthermal cellular response. However, it is impossible to pinpoint a single gene or family of genes that would accurately and reliably justify the patterns of gene expression response under THz exposure.

Identification of stripe rust resistance gene YrBDT in Chinese landrace wheat Baidatou using BSE-seq and BSR-seq.

A new stripe rust resistance gene YrBDT in Chinese landrace wheat Baidatou was mapped to a 943.6-kb interval on chromosome arm 6DS and co-segregated with a marker CAPS3 developed from candidate gene TraesCS6D03G0027300. Stripe rust caused by Puccinia striiformis f. sp. tritici (Pst) is a devastating foliar disease of wheat. Chinese landrace wheat Baidatou has shown high resistance to a broad spectrum of Pst races at both the seedling and adult-plant stages for decades in the Longnan region of Gansu province, a hot spot for stripe rust epidemics. Here, we report fine mapping and candidate gene analysis of stripe rust resistance gene YrBDT in Baidatou. Analysis of F1, F2 plants and F2:3 lines indicated that resistance in Baidatou to Pst race CYR31 was conferred by a single dominant gene, temporarily designated YrBDT. Bulked segregant exome capture sequencing (BSE-seq) analysis revealed 61 high-confidence polymorphic SNPs concentrated in a 5.4-Mb interval at the distal of chromosome arm 6DS. Several SNPs and InDels were also identified by genome mining of DNA sampled from the parents and contrasting bulks. The YrBDT locus was mapped to a 943.6-kb (4,658,322-5,601,880bp) genomic region spanned by markers STS2 and STS3 based on IWGSC RefSeq v2.1, including five putative disease resistance genes. There was high collinearity of the target interval among Chinese Spring RefSeq v2.1, Ae. tauschii AL8/78 and Fielder genomes. The expression level of TraesCS6D03G0027300 showed significant association with Pst infection, and a gene-specific marker CAPS3 developed from TraesCS6D03G0027300 co-segregated with YrBDT suggesting this gene as a candidate of YrBDT. The resistance gene and flanking markers can be used in marker-assisted selection for improvement of stripe rust resistance.

Single gene mutations and prognosis in limited-stage follicular lymphoma treated with radiation therapy.

Radiotherapy is routinely used for management of limited-stage follicular lymphoma (FL), yet half of patients ultimately relapse. We hypothesized that the presence of specific gene mutations may predict outcomes. We performed targeted sequencing of a 69-gene panel in 117 limited-stage FL patients treated with radiotherapy and identified recurrently mutated genes. CREBBP was most frequently mutated, and mutated CREBBP was associated with inferior progression-free survival, though not after false discovery rate adjustment. This association failed to validate in an independent cohort. We conclude that recurrent gene mutations do not predict outcomes in this setting. Alternative biomarkers may offer better prognostic insight.