Journal of Applied Genetics最新文献

Enalapril is an orally administered angiotensin-converting enzyme inhibitor which is widely prescribed to treat hypertension, chronic kidney disease, and heart failure. It is an ester prodrug that needs to be activated by carboxylesterase 1 (CES1). CES1 is a hepatic hydrolase that in vivo biotransforms enalapril to its active form enalaprilat in order to produce its desired pharmacological impact. Several single nucleotide polymorphisms in CES1 gene are reported to alter the catalytic activity of CES1 enzyme and influence enalapril metabolism. G143E, L40T, G142E, G147C, Y170D, and R171C can completely block the enalapril metabolism. Some polymorphisms like Q169P, E220G, and D269fs do not completely block the CES1 function; however, they reduce the catalytic activity of CES1 enzyme. The prevalence of these polymorphisms is not the same among all populations which necessitate to consider the genetic panel of respective population before prescribing enalapril. These genetic variations are also responsible for interindividual variability of CES1 enzyme activity which ultimately affects the pharmacokinetics and pharmacodynamics of enalapril. The current review summarizes the CES1 polymorphisms which influence the enalapril metabolism and efficacy. The structure of CES1 catalytic domain and important amino acids impacting the catalytic activity of CES1 enzyme are also discussed. This review also highlights the importance of pharmacogenomics in personalized medicine.

There are limited number of studies investigating the role of microRNAs (miRNAs) in Aspergillus infections. In this study, we designed an in vitro aspergillosis model to identify differentially expressed Aspergillus-related miRNAs. For this purpose, carcinoma cell lines "A549" and "Calu-3" were infected with Aspergillus fumigatus. Total miRNA was isolated at 0, 1, 6, and 24 h post-infection. Quantitative real-time PCR assay was conducted to screen 31 human miRNAs that were possibly related to aspergillosis. Up- and downregulated miRNAs were detected in the infected cells. Highest level of miRNA expression was detected at 6 h post-infection. miR-21, hsa-miR-186-5p, hsa-miR-490-5p, miR-26a-5p, miR-26b-5p, hsa-miR-424-5p, hsa-miR-548d-3p, hsa-miR-196a-5p, miR-150-5p, miR-17-5p, and hsa-miR-99b-5p were found to be significantly upregulated (p < 0.001) at 6 h after A. fumigatus infection compared with the controls. Among the screened miRNAs, hsa-miR-145-5p (p < 0.001); hsa-miR-583 and hsa-miR-3978 (p < 0.01); and miR-21-5p, hsa-miR-4488, and hsa-miR-4454 (p < 0.05) were found to be downregulated compared with the controls. In conclusion, screening the identified miRNAs may reveal the personal predisposition to aspergillosis, which might be valuable from the perspective of personalized medicine.

Recently, numerous studies including various tissues have been carried out on long non-coding RNAs (lncRNAs), but still, its variability has not yet been fully understood. In this study, we characterised the inter-individual variability of lncRNAs in pigs, in the context of number, length and expression. Transcriptomes collected from muscle tissue belonging to six Polish Landrace boars (PL1-PL6), including half-brothers (PL1-PL3), were investigated using bioinformatics (lncRNA identification and functional analysis) and statistical (lncRNA variability) methods. The number of lncRNA ranged from 1289 to 3500 per animal, and the total number of common lncRNAs among all boars was 232. The number, length and expression of lncRNAs significantly varied between individuals, and no consistent pattern has been found between pairs of half-brothers. In detail, PL5 exhibits lower expression than the others, while PL4 has significantly higher expression than PL2-PL3 and PL5-PL6. Noteworthy, comparing the inter-individual variability of lncRNA and mRNA expression, they exhibited concordant patterns. The enrichment analysis for common lncRNA target genes determined a variety of biological processes that play fundamental roles in cell biology, and they were mostly related to whole-body homeostasis maintenance, energy and protein synthesis as well as dynamics of multiple nucleoprotein complexes. The high variability of lncRNA landscape in the porcine genome has been revealed in this study. The inter-individual differences have been found in the context of three aspects: the number, length and expression of lncRNAs, which contribute to a better understanding of its complex nature.

The chloroplast genomes of five Fritillaria ussuriensis materials from different production areas were comparatively analyzed, atpF and petB were screened as specific DNA barcodes, and the population identification and genetic diversity of F. ussuriensis were analyzed based on them. The F. ussuriensis chloroplast genome showed a total length of 151 515-151 548 bp with a typical tetrad structure and encoded 130 genes. atpF and petB were used to amplify 183 samples from 13 populations, and they could identify 6 and 9 haplotypes, respectively. Joint analysis of the two sequences revealed 18 haplotypes, named H1-H18, with the most widely distributed and most abundant being H4. Ten haplotypes were unique for 7 populations that they could be used to distinguish from others. Haplotype diversity and nucleotide diversity were 0.99 and 2.09 × 10^-3, respectively, indicating the genetic diversity was relatively rich. The results of the intermediary adjacency network showed that H5 was the oldest haplotype, and stellate radiation was centered around it, indicating that population expansion occurred in genuine production areas. This study lays a theoretical foundation for the population identification, genetic evolution, and breed selection of F. ussuriensis.

Streptococcus pyogenes (group A Streptococcus, GAS) is a major human pathogen and causes every year over 600 millions upper respiratory tract onfections worldwide. Untreated or repeated infections may lead to post-infectional sequelae such as rheumatic heart disease, a major cause of GAS-mediated mortality. There is no comprehensive, longitudinal analysis of the M type distribution of upper respiratory tract strains isolated in Poland. Single reports describe rather their antibiotic resistance patterns or focus on the invasive isolates. Our goal was to analyse the clonal structure of the upper respiratory tract GAS isolated over multiple years in Poland. Our analysis revealed a clonal structure similar to the ones observed in high-income countries, with M1, M12, M89, M28, and M77 serotypes constituting over 80% of GAS strains. The M77 serotype is a major carrier of erythromycin resistance and is more often correlated with upper respiratory tract infections than other serotypes.

Genetic information of bean seed traits can be an immense help to the breeder in selection of suitable genotypes and the appropriate breeding strategies. Therefore, the investigation aims to assess the genetic variability and to elucidate the genetic analysis of seed dietary fibre, carbohydrate, seed calcium and phosphorus contents of Phaseolus vulgaris in the high Guinean Savannah zone conditions. 5 × 5 half-diallel crosses of these traits were conducted in randomized complete block design with three replications. Results revealed high differences between five lines beans (p < 0.05), suggesting the sufficient genetic diversity for these traits. High broad sense heritability values were recorded for seed dietary fibre, carbohydrate and seed calcium content, attesting a strong implication of the genetic factors in the control of these traits; thereby, these traits can be improved through regular selection. The ratio GCA/SCA was greater than unity only for seed phosphorus content. It indicates the prevalence of additive gene effect in the involvement of the genetic control for this trait. The combining ability analysis revealed highly significant differences between parental GCA effects and F₁ cross SCA effects. The PB, BI, CT and PR lines beans will prove useful in common bean breeding programmes as donor genotypes, in the development of bean genetic resources for betterment improvement of nutritional traits.

Placental angiogenesis is a pivotal process for feto-maternal circulation and ensures efficient development of the placenta throughout pregnancy. Many factors during in vitro fertilization and embryo transfer procedures may affect placental gene expression and fetus development. The present study aimed to identify differences in angiogenesis-related gene (VEGFA, FGF2, FLT1, and KDR) expression profiles in placentas after assisted reproductive technology fertilization and natural conception in healthy women. In a case-control study, term placentas were collected from Caucasian women after assisted reproductive technology fertilization (N = 20) and after natural conception in women with uncomplicated pregnancy (N = 9). The mRNA expression in placentas was examined for VEGFA, FGF2, FLT1, and KDR genes by real-time quantitative polymerase chain reaction (RT-qPCR). Group stratification was performed for comparison of investigated genes between the type of embryo transferred (fresh/frozen), place of tissue donation (center/margin), and newborns' gender (male/female). In the ART placentas, significant down-regulation of VEGFA gene (p = 0.016) and up-regulation of FLT1 (p = 0.026) and KDR (p < 0.001) gene receptors were observed. Genes encoding VEGFA receptors were up-regulated in both fresh (ET) and frozen (FET) embryo transfer groups compared to controls. For the FLT1 gene, a statistically significant difference was observed between the frozen embryo transfer group and the controls (p = 0.032). Relative expression of KDR was significantly higher for both embryo transfer groups compared to controls (p < 0.001) and between ET and FET (p = 0.002). No statistically significant differences were observed between placental expression in different places of tissue donation and newborns' gender. We observed differences in the placental expression of VEGFA and its receptors FLT1 and KDR in pregnancies after assisted reproductive technology compared to naturally conceived pregnancies. More research is needed to clarify these alterations that may affect placental development and fetal health.

Phenotypical innovations during evolution are caused by novel mutations, which are usually heterozygous at the beginning. The gene expressions on two alleles of these mutation sites are not necessarily identical, leading to flexible allele-specific regulation in cell systems. We retrieve the transcriptome data of normal and non-small cell lung cancer (NSCLC) tissues from 47 African Americans (AA) and 50 European Americans (EA). We analyze the differentially expressed genes (DEGs) in NSCLC as well as the tumor-specific mutations. Expression and mutation profiles show convergent evolution in AA and EA populations. The tumor-specific mutations are poorly overlapped, but many of them are located in the same genes, mainly oncogenes and tumor suppressor genes. The DEGs in tumors are majorly caused by the mutated alleles rather than normal alleles. The relative expressions of mutated alleles are highly correlated between AA and EA. The differential expression in NSCLC is predominantly mediated by the mutated alleles on heterozygous sites. This molecular mechanism underlying NSCLC oncogenesis is conserved across different human populations, exhibiting convergent evolution. We present this novel angle that differential expression analysis should be performed separately for different alleles. Our ideas should greatly benefit the cancer community.

Oral tongue squamous cell carcinoma (OTSCC) is the most common malignancy type among males across the world. However, analysis of molecular markers could be useful in detecting the early-stage OTSCC, which would allow optimal clinical treatments and prolong the survival rate of patients consequently. The study has the objective of detecting the role of salivary biomarkers based on gene promoter hypermethylation. Sample data from 45 OTSCC and normal groups were analyzed to exhibit the methylation levels of salivary biomarkers (TRH, FHIT, MGMT, p16, and RASSF1A). The specificity and sensitivity analysis of methylation biomarkers was conducted in addition to the receiver operating characteristic (ROC) curve for both early-stage and advanced OTSCC stages. Quantitative data findings showed the perfect sensitivity and specificity for TRH, MGMT, p16, and RASSF1A with 100%, and > 90%, respectively. In addition, the results indicated an inefficient area under curves (> 0.7) for these biomarkers to detect the OTSCC. There were no significant differences observed between TRH and FHIT and p16 and MGMT based on the Wilcoxon signed-rank test. The methylation statuses of genes TRH, RASSF1A, p16, and MGMT might become utilized as predictive biomarkers for clinical application in early diagnosis of OTSCC and noninvasive oral cancer screening.

The Homeobox (HOX) gene family is essential to regulating cellular processes because it maintains the exact coordination required for tissue homeostasis, cellular differentiation, and embryonic development. The most distinctive feature of this class of genes is the presence of the highly conserved DNA region known as the homeobox, which is essential for controlling their regulatory activities. Important players in the intricate process of genetic regulation are the HOX genes. Many diseases, especially in the area of cancer, are linked to their aberrant functioning. Due to their distinctive functions in biomedical research-particularly in the complex process of tumor advancement-HOXA9 and HOXB9 have drawn particular attention. HOXA9 and HOXB9 are more significant than what is usually connected with HOX genes since they have roles in the intricate field of cancer and beyond embryonic processes. The framework for a focused study of the different effects of HOXA9 and HOXB9 in the context of tumor biology is established in this study.