Journal of Applied Genetics最新文献

Sweet corn has emerged as a favorite food item worldwide owing to its kernel sweetness. However, traditional sweet corn cultivars are poor in provitamin-A (proA) and essential amino acids, viz., lysine and tryptophan. So far, no sweet corn hybrid with high nutritional qualities has been commercialized elsewhere. Here, we analyzed accumulation of provitamin-A (proA), lysine, and tryptophan in a set of mutant versions of (i) crtRB1-, (ii) o2-, and (iii) crtRB1 + o2-based sweet corn inbreds and hybrids with (iv) traditional sweet corn (wild-type: O2 + CrtRB1). The crtRB1- and crtRB1 + o2-based genotypes possessed significantly higher proA (17.31 ppm) over traditional sweet corn (2.83 ppm), while o2- and crtRB1 + o2-based genotypes possessed significantly higher lysine (0.345%) and tryptophan (0.080%) over traditional sweet corn (lysine 0.169%, tryptophan 0.036%). Late sowing favored high kernel lysine, proA, and green cob yield among hybrids. Sweetness (17.87%) among the improved inbreds and hybrids was comparable to the original sweetcorn genotypes (17.84%). Among the four genotypic classes, crtRB1 + o2-based improved genotypes showed stronger association among traits over genotypes with o2 and crtRB1 genes alone. Significant association was observed among (i) proA and BC (r = 0.99), (ii) proA and BCX (r = 0.93), (iii) lysine and tryptophan (r = 0.99), and (iv) green cob yield with fodder yield (r = 0.73) in sweet corn hybrids. The study demonstrated that combining crtRB1 and o2 genes did not pose any negative impact on nutritional, yield, and agronomic performance. Sweet corn with crtRB1 + o2 assumes significance for alleviating malnutrition through sustainable and cost-effective approach.

Neoadjuvant chemotherapy is the foundation treatment for triple-negative breast cancer (TNBC) and frequently results in pathological complete response (pCR). However, there are large differences in clinical response and survival after neoadjuvant chemotherapy of TNBC patients. The aim was to identify genes whose expression significantly associates with the efficacy of neoadjuvant chemotherapy in patients with TNBC. Transcriptomes of 46 formalin-fixed paraffin-embedded (FFPE) tumor samples from TNBC patients were analyzed by RNA-seq by comparing 26 TNBCs with pCR versus 20 TNBCs with pathological partial remission (pPR). Subsequently, we narrowed down the list of genes to those that strongly correlated with drug sensitivity of 63 breast cancer cell lines based on Dependency Map Consortium data re-analysis. Furthermore, the list of genes was limited to those presenting specific expression in breast tumor cells as revealed in three large published single-cell RNA-seq breast cancer datasets. Finally, we analyzed which of the selected genes were significantly associated with overall survival (OS) in TNBC TCGA dataset. A total of 105 genes were significantly differentially expressed in comparison between pPR versus pCR. As revealed by PLSR analysis in breast cancer cell lines, out of 105 deregulated genes, 42 were associated with sensitivity to docetaxel, doxorubicin, paclitaxel, and/or cyclophosphamide. We found that 24 out of 42 sensitivity-associated genes displayed intermediate or strong expression in breast malignant cells using single-cell RNAseq re-analysis. Finally, 10 out of 24 genes were significantly associated with overall survival in TNBC TCGA dataset. Our RNA-seq-based findings suggest that there might be transcriptomic signature consisted of 24 genes specifically expressed in tumor malignant cells for predicting neoadjuvant response in FFPE samples from TNBC patients prior to treatment initiation. Additionally, nine out of 24 genes were potential survival predictors in TNBC. This group of 24 genes should be further investigated for its potential to be translated into a predictive test(s).

Background: The activation of TGF-β pathway can facilitate tumorigenesis. Understanding the TGF-related genes (TRGs) in oral cancer and determining their prognostic value is of utmost importance.

Methods: The TRGs were selected to develop a prognostic model based on lasso regression. Oral cancer patients were classified into high-risk and low-risk groups based on the risk model. Subsequently, multivariate COX regression was employed to identify the prognostic marker. Additionally, the expression of SMURF2 was validated using quantitative real-time polymerase chain reaction (qRT-PCR) and the Human Protein Atlas (HPA) database. To investigate the relationship between SMURF2 expression and immune cell infiltrations, we conducted single-sample Gene Set Enrichment Analysis (ssGSEA) analyses.

Results: We identified 16 differentially expressed TRGs in oral cancer, all of which showed upregulation. From these, we selected eight TRGs as prognostic signatures. Furthermore, the high-risk group demonstrated lower infiltration levels of immune cells, immune score, and higher tumor purity. Interestingly, we also found that SMURF2 serves as an independent prognostic biomarker. SMURF2 was upregulated in oral cancer, as confirmed by public databases and qRT-PCR analysis. Importantly, our results indicate a close association between SMURF2 expression and the immune microenvironment.

Conclusion: The 8-TRG signature prognosis model that we constructed has the ability to predict the survival rate and immune activity of oral cancer patients. SMURF2 could be effective in recognizing prognosis and evaluating immune efficacy for oral cancer.

Long noncoding RNAs (lncRNAs) play a role in the emergence and progression of several human tumors, including luminal B breast cancer (BC). The biological functions and potential mechanisms of lncRNA myocardial infarction-associated transcripts (MIAT) in luminal B BC, on the contrary, are unknown. In this work, we used UALCAN database analysis to find high expression of lncRNA MIAT in luminal BC tissues and also confirmed high levels of lncRNA MIAT expression in luminal B BC tissues and cells. In vitro knockdown of MIAT inhibited the proliferation, migration, and invasion of BT474 cells. In addition, we found that miR-150-5p levels were significantly reduced in luminal B BC specimens and cells, and miR-150-5p levels were significantly increased when MIAT was knocked down. And TIMER database analysis showed that MIAT was positively associated with PDL1. Through bioinformatic tools and in vitro experiments, lncRNA MIAT could function as a competitive endogenous RNA (CeRNA) to further regulate programmed cell death ligand 1 (PDL1) expression by directly sponging miR-150-5p. In conclusion, our data suggest that MIAT, an oncogene, may sponge miR-150-5p to regulate PDL1 expression and affect proliferation, migration, and invasion in luminal B BC in vitro.

Chromatinopathies (CPs), a group of rare inborn defects characterized by chromatin state imbalance, have evolved from initially resembling Cornelia de Lange syndrome to encompass a wide array of genetic diseases with diverse clinical presentations. The CPs classification now includes human developmental disorders caused by germline mutations in epigenes, genes that regulate the epigenome. Recent advances in next-generation sequencing have enabled the association of 154 epigenes with CPs, revealing distinctive DNA methylation patterns known as episignatures.It has been shown that episignatures are unique for a particular CP or share similarities among specific CP subgroup. Consequently, these episignatures have emerged as promising biomarkers for diagnosing and treating CPs, differentiating subtypes, evaluating variants of unknown significance, and facilitating targeted therapies tailored to the underlying epigenetic dysregulation.The following review was conducted to collect, summarize, and analyze data regarding CPs in such aspects as clinical evaluation encompassing long-term patient care, underlying epigenetic changes, and innovative molecular and bioinformatic methodologies that have been devised for the assessment of CPs. We have also shed light on promising novel treatment options that have surfaced in recent research and presented a synthesis of ongoing clinical trials, contributing to the current understanding of the dynamic and evolving nature of CPs investigation.

Deteriorating climatic conditions and increasing human population necessitate the development of robust plant varieties resistant to harsh environments. Manipulation of regulatory proteins such as transcription factors (TFs) and RNA-binding proteins (RBPs) would be a beneficial strategy in this regard. Further, understanding the complex interconnections between different classes of regulatory molecules would be essential for the identification of candidate genes/proteins for trait improvement. Most studies to date have analysed the roles of TFs or RBPs individually, in conferring stress resilience. However, it would be important to identify dominant/upstream TFs and RBPs inducing widespread transcriptomic alterations through other regulators (i.e., other TFs/RBPs targeted by the upstream regulators). To this end, the present study employed a transcriptome meta-analysis and computational approaches to obtain a comprehensive overview of regulatory interactions. This work identified dominant TFs and RBPs potentially influencing stress-mediated differential expression of other regulators, which could in turn influence gene expression, and consequently, physiological responses. Twenty transcriptomic studies [related to (i) UV radiation, (ii) wounding, (iii) salinity, (iv) cold, and (v) drought stresses in Arabidopsis thaliana] were analysed for differential gene expression, followed by the identification of differentially expressed TFs and RBPs. Subsequently, other TFs and RBPs which could be influencing these regulators were identified, and their interaction networks and hub nodes were analysed. As a result, an interacting module of Basic Leucine Zipper (bZIP) family TFs as well as Heterogeneous nuclear ribonucleoproteins (hnRNP) and Glycine-rich protein (GRP) family RBPs (among other TFs and RBPs) were shown to potentially influence the stress-induced differential expression of other TFs and RBPs under all the considered stress conditions. Some of the identified hub TFs and RBPs are known to be of major importance in orchestrating stress-induced transcriptomic changes influencing a variety of physiological processes from seed germination to senescence. This study highlighted the gene/protein candidates that could be considered for multiplexed genetic manipulation - a promising approach to develop robust, multi-stress-resilient plant varieties.

Noonan syndrome (NS; OMIM 163950) is an autosomal dominant RASopathy with variable clinical expression and genetic heterogeneity. Clinical manifestations include characteristic facial features, short stature, and cardiac anomalies. Variants in protein-tyrosine phosphatase, non-receptor-type 11 (PTPN11), encoding SHP-2, account for about half of NS patients, SOS1 in approximately 13%, RAF1 in 10%, and RIT1 each in 9%. Other genes have been reported to cause NS in less than 5% of cases including SHOC2, RASA2, LZTR1, SPRED2, SOS2, CBL, KRAS, NRAS, MRAS, PRAS, BRAF, PPP1CB, A2ML1, MAP2K1, and CDC42. Several additional genes associated with a Noonan syndrome-like phenotype have been identified. Clinical presentation and variants in patients with Noonan syndrome are this study's objectives. We performed Sanger sequencing of PTPN11 hotspot (exons 3, 8, and 13). We report molecular analysis of 61 patients with NS phenotype belonging to 58 families. We screened for hotspot variants (exons 3, 8, and 13) in PTPN11 gene by Sanger sequencing. Twenty-seven patients were carrying heterozygous pathogenic variants of PTPN11 gene with a similar frequency (41.4%) compared to the literature. Our findings expand the variant spectrum of Moroccan patients with NS phenotype in whom the analysis of hotspot variants showed a high frequency of exons 3 and 8. This screening test allowed us to establish a molecular diagnosis in almost half of the patients with a good benefit-cost ratio, with appropriate management and genetic counseling.

Best linear unbiased prediction (BLUP) is widely used in plant research to address experimental variation. For phenotypic values, BLUP accuracy is largely dependent on properly controlled experimental repetition and how variable components are outlined in the model. Thus, determining BLUP robustness implies the need to evaluate contributions from each repetition. Here, we assessed the robustness of BLUP values for simulated or empirical phenotypic datasets, where the BLUP value and each experimental repetition served as dependent and independent (feature) variables, respectively. Our technique incorporated machine learning and partial dependence. First, we compared the feature importance estimated with the neural networks. Second, we compared estimated average marginal effects of individual repetitions, calculated with a partial dependence analysis. We showed that contributions of experimental repetitions are unequal in a phenotypic dataset, suggesting that the calculated BLUP value is likely to be influenced by some repetitions more than others (such as failing to detect simulated true positive associations). To resolve disproportionate sources, variable components in the BLUP model must be further outlined.

Since its initial identification, the Forkhead Box P2 gene (FOXP2) has maintained its singular status as the archetypal monogenic determinant implicated in Mendelian forms of human speech and language impairments. Despite the passage of two decades subsequent to its discovery, extant literature remains disproportionately sparse with regard to case-specific instances and loci of mutational perturbations. The objective of the current investigation centers on furnishing an enriched delineation of both its clinical manifestations and its mutational heterogeneity. Clinical phenotypes and peripheral blood samples were assiduously amassed from familial subjects. Whole-exome sequencing and Sanger sequencing methodologies were deployed for the unambiguous identification of potential genetic variants and for corroborating their co-segregation within the family pedigree. An exhaustive review of published literature focusing on patients manifesting speech and language disorders consequent to FOXP2 genetic anomalies was also undertaken. The investigation yielded the identification of a novel heterozygous variant, c.661del (p.L221Ffs*41), localized within the FOXP2 gene in the proband, an inheritance from his symptomatic mother. The proband presented with an array of symptoms, encompassing dysarthric speech, deficits in instruction comprehension, and communicative impediments. In comparison, the mother exhibited attenuated symptoms, including rudimentary verbalization capabilities punctuated by pronounced stuttering and dysarthria. A comprehensive analysis of articles archived in the Human Gene Mutation Database (HGMD) classified under "DM" disclosed the existence of 74 patients inclusive of the subjects under current examination, sub-divided into 19 patients with null variants, 5 patients with missense variants, and 50 patients with gross deletions or complex genomic rearrangements. A conspicuous predominance of delayed speech, impoverished current verbal abilities, verbal comprehension deficits, and learning difficulties were observed in patients harboring null or missense FOXP2 variants, as compared to their counterparts with gross deletions or complex rearrangements. Developmental delays, hypotonia, and craniofacial aberrations were exclusive to the latter cohort. The elucidated findings augment the existing corpus of knowledge on the genetic architecture influencing both the proband and his mother within this specified familial context. Of critical importance, these discoveries furnish a robust molecular framework conducive to the prenatal diagnostic evaluations of prospective progeny within this familial lineage.