Journal of Applied Genetics最新文献

Head and neck squamous cell carcinoma (HNSC) is a diverse group of tumors arising from oral cavity, oropharynx, larynx, and hypopharynx squamous epithelium, posing significant morbidity. Aquaporins (AQPs) are membrane proteins forming water channels, some associated with carcinomas. Chromobox (CBX) family is known to modulate physiological and oncological processes. In our study, we analyzed AQPs and CBXs having significant expression followed by their prognostic and mutational assessment. Next, we performed enrichment and tumor infiltration analysis followed by HPA validation. Lastly, we established a 3-node miRNA-TF-mRNA regulatory network and performed protein-protein docking of the highest-degree subnetwork motif between TF and mRNA. Significant upregulation of CBX3/2 and downregulation of AQP3/5/7 correlated with poor overall survival (OS) in HNSC patients. The most significant pathway, GO-BP, GO-MF, and GO-CC terms associated with AQP3 and CBX3 were passive transport by aquaporins, response to vitamin, glycerol channel activity, and condensed chromosome, centromeric region. AQP3 negatively correlated with ${\text{CD}4}^{+}$ T cells, positively with ${\text{CD}8}^{+}$ T cells and B cells, and negatively with tumor purity, whereas CBX3 positively correlated with ${\text{CD}4}^{+}$ T cells, negatively with ${\text{CD}8}^{+}$ T cells and B cells, and positively with tumor purity. Three-node miRNA-TF-mRNA regulatory network revealed a highest-degree subnetwork motif comprising one TF (SMAD3), one miRNA (miR-423-5p), and one mRNA (AQP3). Protein-protein interaction studies suggested a direct interaction between AQP3 and Smad3 proteins. We concluded that AQP3 and CBX3 hold potential as treatment strategies and individual prognostic biomarkers, while further protein-protein interaction studies of AQP3 could offer insights into its interactions with Smad3 proteins.

This case study illustrates a multidisciplinary diagnostic and therapeutic model of care for a 7-year-old male with Lamb-Shaffer syndrome (LAMSHF). LAMSHF is an ultra-rare genetic neurodevelopmental disorder, caused by heterozygous alterations in the SOX5 gene. An integrative model of therapy of cognitive functions and speech is described. The presented approach allows the development of language competences through stimulation of basic cognitive functions, which allows the learning of the abstract rules of an inflected language. A surprising, unexpected improvement in the cognitive functioning of the child was observed (both in terms of reasoning and speech), as well as an increase in his independence. The clinically important problem of the need for continued stimulation of cognitive development, in spite of the unfavourable prognosis associated with LAMSHF, is highlighted.

Water-Soluble Palm Fruit Extract (WSPFE) has been shown to confer anti-diabetic effects in the Nile rat (NR) (Arvicanthis niloticus). Liquid and powder WSPFE both deterred diabetes onset in NRs fed a high-carbohydrate (hiCHO) diet, but the liquid form provided better protection. In this study, NRs were fed either a hiCHO diet or the same diet added with liquid or powder WSPFE. Following feeding of the diets for 8 weeks, random blood glucose levels were measured to categorize NRs as either diabetes-resistant or diabetes-susceptible, based on a cut-off value of 75 mg/dL. Livers were then obtained for Illumina HiSeq 4000 paired end RNA-sequencing (RNA-Seq) and the data were mapped to the reference genome. Consistent with physiological and biochemical parameters, the gene expression data obtained indicated that WSPFE was associated with protection against diabetes. Among hepatic genes upregulated by WSPFE versus controls, were genes related to insulin-like growth factor binding protein, leptin receptor, and processes of hepatic metabolism maintenance, while those downregulated were related to antigen binding, immunoglobulin receptor, inflammation- and cancer-related processes. WSPFE supplementation thus helped inhibit diabetes progression in NRs by increasing insulin sensitivity and reducing both the inflammatory effects of a hiCHO diet and the related DNA-damage compensatory mechanisms contributing to liver disease progression. In addition, the genetic permissiveness of susceptible NRs to develop diabetes was potentially associated with dysregulated compensatory mechanisms involving insulin signaling and oxidative stress over time. Further studies on other NR organs associated with diabetes and its complications are warranted.

The cultivation of nearly 10,000 indigenous rice landraces in the North-Eastern Hill (NEH) region by various ethnic groups creates opportunities for the utilization of unique landraces through systematic evaluation of genetic variability. In the present study, a set of 102 rice landraces were assessed based on morphological and SSR markers, and five checks in augmented design vis-à-vis high-yielding rice genotypes with stable performance were identified. The presence of high estimates of heritability, genotypic coefficient of variation, and genetic advance over mean indicated the predominance of additive gene action, which necessitated the effectiveness of selection in augmenting productivity. A total of 83.73% of the total variation was accounted by the first five principal components. A total of 132 alleles were detected, with an average of 3 alleles per locus. The PIC values ranged from 0.01 to 0.70, with an average of 0.40. Based on F_ST value (5.1%), significant differences between the genotypes of Arunachal Pradesh and Sikkim were observed. The percentage of variation among the population, among individuals within the population, and within individuals was 5.14, 75.66, and 19.2%, respectively. Both Nei's genetic distance and model-based clustering have differentiated the genotypes into five distinct clusters. Principal coordinate analysis illustrated that the genotypes of Manipur were scattered in all quadrants, showing that they are highly diverse, while the genotypes of Nagaland, Sikkim, and Meghalaya were found together, which represent the chance of mixing of the population at a certain point in time. Markers, namely RM 474, OSR 13, RM 413, and RM 259, were found to be associated with key traits for increasing yielding ability of plant. In a stability evaluation based on AMMI analysis and multi-trait genotype-ideoptype distance matrix (MGIDI), genotypes, namely Jyotrirmayie, RCPL 1-411, Tsamum firri, Ching Phouren, Rato Bhan Joha, MN-47, and Tara bali, were selected with higher yield potential.

Doublesex and Mab-3 (DMRT) gene family is a diverse group of transcriptional factors crucially involved in sex differentiation and biological processes such as body growth and differentiation in vertebrates. In this study, we analyzed DMRT genes structural characterization and physiochemical properties, and elucidated their functional role as a ligand of different gonadal receptors including androgen (AR), estrogen β (ER-β), estrogen γ (ER-γ), and progesterone (PR). All six genes of the DMRT gene family in grass carp (Ctenopharyngodon Idella Valenciennes, 1844) exhibited an acidic nature. These DMRT genes are primarily localized in the nucleus, where they play a role in DNA binding via doublesex DNA binding motif. All the DMRT gene pairs are under strong purifying selection with two segmental duplications envisaged about 18.30 (DMRT3a/DMRTA2) and 24.90 (DMRT2b/DMRT2a) million years ago (MYA). Recombination analysis revealed six potential recombinant breakpoints posing substantial evolutionary pressure for diverse cellular functioning of DMRT isoforms. Moreover, the DMRTA1 protein had a highest binding affinity of - 270.42 and - 267.16 for androgen receptors (AR) and progesterone receptors (PR), whereas, for estrogen receptors ER-β and ER-γ, the maximum binding affinity was observed with DMRT2a and DMRT2b proteins showing a docking score of - 254.22 and - 261.71, respectively. First time we studied the binding scores and interface residues of the DMRT genes as a ligand of gonadal receptors that play a crucial role in fish growth, sex development and differentiation, and spermatogenesis and oocyte maturation. The present study provides a molecular basis for DMRT genes in grass carp that may serve as a reference for in-depth phylogenomic study in other species.

Dietary lipids provide energy, are cellular structural components, and are involved in physiological processes. Lipids are the dietary source in supplementary diet experiments in pigs. This study aims to investigate the dietary effects of PUFAs on the hepatic transcriptome and physiological pathways of two diets on two pig breeds. Polish Landrace (PL: n = 6) and six PLxDuroc (PLxD: n = 6) pigs were fed with a normal diet (n = 3) or PUFAs-enriched healthy diet (n = 3), and the hepatic miRNA profiles were studied for weighted gene co-expression network analysis biological interactions between gene networks and metabolic pathways of DE miRNA genes. The study identified trait-associated modules that were significantly associated with four phenotypic traits in the dietary groups of PL and PLxD: meat colour (a*), shoulder subcutaneous fat thickness, conductivity 24 h post-mortem (PE24), and ashes. Trait-wise, a large set of co-expressed miRNAs of porcine liver were identified in these trait-associated significant modules (9, 7, 2, and 8) in PL and PLxD. Each module is represented by a module eigengene (ME). Forty-four miRNAs out of 94 miRNAs interacted with 6719 statistically significant target genes with a target score > 90. The GO/pathway analysis showed association with pathways including regulation of metallopeptidase activity, sebaceous gland development, collagen fibril organization, WNT signalling, epithelial tube morphogenesis, etc. The study showed the differences in miRNA expression between the dietary groups of PL and PLxD breeds. Hub genes of discovered miRNA clusters can be considered predicted miRNA genes associated with PE24, meat colour, shoulder subcutaneous fat thickness, and ashes. Discovered target genes for miRNA clusters play significant roles in biological functions such as (i) muscle and body growth development, (ii) different cellular processes and developments, (iii) system development, and (iv) metabolic processes.

Miniature inverted-repeat transposable elements (MITEs) are a potent source of polymorphisms in plant genomes. A genotyping system, named DcS-ILP, based on polymorphic insertions of Stowaway MITEs (DcStos) localized in introns and identified in the reference genome DH1, has been developed for carrot. Here, we report an extension of the DcS-ILP genotyping system by incorporation of non-reference insertions identified in resequenced genomes representing the eastern gene pool. We genotyped 52 carrot accessions representing the eastern and western carrot gene pools with 92 markers developed previously (western DcS-ILP panel) together with 84 newly developed markers (eastern DcS-ILP panel). Overall, the DcS-ILP markers revealed a highly structured genetic diversity separating the eastern and the western carrot accessions at K = 2 and differentiating Indian breeding lines from the eastern accessions at K = 3. The eastern DcS-ILP panel proved to be more robust with respect to the eastern carrot gene pool, while it provided little information on the western accessions, as many of the DcSto insertions present in the eastern gene pool were absent in the western gene pool. As the western carrot accessions represent improved cultivars, DcSto insertional polymorphisms allowed detection of a selection-driven bottleneck at the improvement stage. Selection in the course of the improvement stage generally operated on standing variation, as the subset of DcSto insertions present in the western carrot likely originated from transposition events preceding the separation of both gene pools. However, occasional frequency shifts in the opposite direction were also revealed, possibly indicating selection for favorable variants associated with DcSto insertions.

Breast cancer (BC) is characterized by the increase of malignant cells in the breast. The malignant cells begin in the lining of the breast milk glands or ducts (ductal epithelium). BC is the most frequent cancer in women, but it may also occur in males. Long non-coding RNAs (lncRNA) have been demonstrated to control the development and incidence of cancer. However, some lncRNAs experience potential changes in BC, but their role has not been well studied. LINC01279 is known as a valuable biomarker in gastric cancer but has not yet been studied in BC. Changes in LINC01279 expression levels in BC samples were investigated by microarray. Q-PCR was also used to evaluate the expression of LINC01279 in the tumor and normal adjacent samples of 30 BC patients. The LINC01279 co-expressed gene module was discovered using weighted gene correlation network analysis (WGCNA) on the relevant dataset. The top ten hub genes were determined using gene ontology (GO) functional enrichments on the co-expressed gene module. The results of the bioinformatics study showed an increase in LINC01279 expression levels (log2FC = 3.228749561, adj.P.Val = 1.69E - 12) in tumor samples compared to normal marginal tissue. Q-PCR results also showed a significant increase in LINC01279 expression (P-value = 0.0005) in tumor samples. WGCNA analysis identified that the black module is the LINC01279 co-expressed module, and functional annotation analysis of black module genes enriched in significant cancer-related pathways and processes, including cell growth and/or maintenance, regulation of immune response, regulation of cell proliferation, and epithelial-to-mesenchymal transition (EMT). Regarding the real-time PCR results, the analysis of expression patterns has illuminated a distinct association between the heightened expression levels of LINC01279, and the stages of cancer progression as well as the metastatic potential of tumors. However, intriguingly, our observations have failed to reveal any statistically significant correlations between the relative expression of LINC01279 and tumor grade classification, or the presence of ER, PR, and HER2 biomarkers. The present study could provide a new perspective on the molecular regulatory. Processes associated with BC pathogenic mechanisms are linked to the LINC01279, although further research is needed on the possible role of this lncRNA in BC.

In the monosomy 1p36 deletion syndrome, the role of DNA methylation in the genomic stability of the 1p36 region remains elusive. We hypothesize that changes in the methylation pattern at the 1p36 breakpoint hotspot region influenced the chromosomal breakage leading to terminal deletions. From the monosomy 1p36 material collection, four cases with 4.0 to 5.5 Mb terminal deletions and their parents were investigated. DNA samples were assessed by targeted bisulfite sequencing (NimbleGen SeqCap Epi) to examine DNA methylation status in the 1p36 hotspot region at single-base resolution as compared to the chromosomal hotspot regions, 9p22, 18q21.1, and 22q11.2. Additionally, in in silico assessment, the mean GC content of various classes of repeats in the genome and especially in the breakpoint regions was evaluated. A complex landscape of DNA methylation in the 1p36 breakpoint hotspot region was found. Changes in DNA methylation level in the vicinity of the breakpoint in the child's DNA when compared to parents' and control DNA were observed, with a shift from 15.1 to 70.8% spanning the breakpoint region. In the main classes of evaluated repeats, higher mean GC contents in the 1p36 breakpoint region (47.06%), 22q11.2 (48.47%), and 18q21.1 (44.21%) were found, compared to the rest of the genome (40.78%). The 9p22 region showed a lower GC content (39.42%) compared to the rest of the genome. Both dysregulation of DNA methylation and high GC content were found to be specific for the 1p36 breakpoint hotspot region suggesting that methylation abnormalities could contribute to aberrations at 1p36.

Northern corn leaf blight (NLB) caused by Setosphaeria turcica (Luttrell) Leonard & Suggs is a severe foliar disease in maize. Resistance to NLB is complexly inherited and controlled by several quantitative trait loci (QTL) distributed across the genome. Phenotype and DNA marker-based selection for resistance to NLB is expected to be effective. Hence, an investigation was carried out to predict the genetic value of selection candidates for resistance to NLB and compare the accuracies of genomic prediction in two F_2:3 populations of two crosses (CM212 × MAI172; CM202 × SKV50) derived from contrasting parents. Linkage analysis using 297 polymorphic SNPs in population-1 and 290 polymorphic SNPs in population-2 revealed ten linkage groups spanning 3623.88 cM and 4261.92 cM with an average distance of 12.40 cM and 14.9 cM in population-1 and population-2, respectively. Location-wise and pooled data across locations identified common QTLs on linkage groups 1 and 6 in population-1 and 3 and 8 in population-2. The prediction accuracy of the QTL mapping (9.92 and 9.10 for population-1 and population-2, respectively) was based on only a few markers, which explained higher percent phenotypic variation. The prediction accuracies of the genomic estimated breeding values in the present investigation were relatively low in population-1 (0.24 to 0.26) and population-2 (0.29-0.32) compared to the expected accuracies. This could be due to fewer polymorphic markers and a small training/population size. Though the GS prediction accuracies were relatively low, they were significantly higher than QTL mapping, which promises better genetic gain per cycle. The resistant progenies from both populations were advanced to derive inbred lines and crossed with four different testers in line × tester mating design to test for their combining ability and effectiveness of genomic selection. High overall general combining ability was exhibited by 21 inbred lines. Among F₁s, 48% were assigned high overall specific combining ability status. Out of the 136 single crosses, seven recorded significant positive standard heterosis over the best check for grain yield. Twenty-five inbreds with high GEBVs were crossed with four testers to obtain 100 F₁s and evaluated for their response to NLB. The majority of hybrids displayed moderate to resistant reaction to NLB either in combination with susceptible or resistant testers indicating the effectiveness of selection based on high GEBVs.