Journal of Applied Genetics最新文献

Infertility presents a substantial challenge for women of reproductive age, exerting profound effects on both individual well-being and healthcare systems. Despite its critical role in folate and homocysteine pathways, the influence of methylenetetrahydrofolate reductase (MTHFR) on the success of assisted reproductive techniques (ART) remains insufficiently understood. This knowledge gap impedes the development of personalized therapeutic strategies. Our study seeks to elucidate the relationship between MTHFR and ART outcomes, exploring potential mediators to enhance treatment efficacy. A cohort of 311 women with infertility was recruited for our study. Multivariate linear models were utilized to evaluate the relationship between the MTHFR 677T allele (a missense mutation resulting in an alanine to valine substitution) and the efficacy of ART, including both treatment outcomes and the number of ART cycles required. Sequential mediation analysis was conducted to elucidate the potential mediators influencing ART efficacy. The MTHFR 677T allele carried by infertile women was associated with a 17-51% reduction in ART efficacy (P < 0.05). This encompassed poorer overall ART outcomes, such as clinical pregnancy and live birth rates, as well as an increased number of ART cycles. Sequential mediation analysis suggested that anti-Müllerian hormone (AMH) and age may act as mediators modulating the impact of the MTHFR 677T allele on ART treatment efficacy. This study has unveiled the intricate connection between MTHFR 677T allele and ART treatment efficacy in infertile women, shedding light on the mediating role of AMH and age.

Hemophilia B is a disease that affects the human coagulation system, causing the absence or deficiency of coagulation factor IX, which may manifest itself in uncontrolled bleeding that is life-threatening to patients. Due to its inheritance, the disease more often affects men, and the severity of symptoms directly correlates with the concentration of the missing factor IX; hence, the aim of therapy is to maintain it at a level that allows for sufficient hemostasis. The basic model of treatment offered to patients is based on primary prevention with coagulation factor IX with a prolonged half-life, which, however, does not solve the numerous problems faced by patients. An innovative proposal that, despite initial concerns, is becoming more and more popular every day is the recently approved genetic therapy in Europe, which uses viral vectors to transfer the correct gene that encodes coagulation factor IX. The introduction of a recombinant gene in place of its defective counterpart seems to be a promising solution and the beginning of a new era in which genetic therapies have a chance to develop their full potential and replace existing therapeutic regimens.

Phosphorus (P) and water are essential for plant growth and development, exerting a significant influence on global crop production. The phosphate transporter (PHT) gene family plays a pivotal role in phosphate (Pi) uptake, transport, and homeostasis under diverse environmental conditions. In this study, we conducted a comprehensive genome-wide identification and characterization of the PHT gene family in Avena sativa. A total of 32 non-redundant AsPHT genes were identified in the OT3098 genome, classified into two subfamilies: AsPHT1 (21 genes) and AsPHO (11 genes). AsPHT1 proteins were predominantly hydrophobic with one or two exons, whereas AsPHO proteins were hydrophilic, exhibiting a more complex structure with 13-15 exons. Cis-regulatory element analysis revealed an abundance of hormone- and stress-responsive elements in the promoters of AsPHT genes, indicating their potential roles in adaptive responses to Pi and water deficiency. Gene expression profiling under low Pi and drought conditions demonstrated differential expression of 22 AsPHT genes in roots and leaves at the seedling stage, with distinct responses to the two stresses, highlighting the functional diversity of the AsPHT gene family. These findings provide valuable insights into the molecular mechanisms underlying Pi and water acquisition in oats and offer potential applications for developing varieties with enhanced Pi use efficiency and drought tolerance.

Microbial metagenomic identification is generally attributed to the specificity and type of the bioinformatic tools, including classifiers and visualizers. In this study, the performance of two major classifiers, Centrifuge and Kraken2, and two visualizers (Recentrifuge and Krona) has been thoroughly investigated for their efficiency in the identification of the microorganisms using the Whole-Genome Sequence (WGS) database and four targeted databases including NCBI, Silva, Greengenes, and Ribosomal Database Project (RDP). Two standard DNA metagenomic library replicates, Zymo and Zymo-1, were used as quality control. Results showed that Centrifuge gave a higher percentage of Pseudomonas aeruginosa, Escherichia coli, and Salmonella enterica identification than Kraken2. Compared to Recentrifuge, Kraken2 was more accurate in identifying Staphylococcus aureus, Listeria monocytogenes, Bacillus subtilis, and Cryptococcus neoformans. The results of the rest of the detected microorganisms were generally consistent with the two classifiers. Regarding visualizers, both Recentrifuge and Krona provided similar results regarding the abundance of each microbial species regardless of the classifier used. The differences in results between the two mentioned classifiers may be attributed to the specific algorithms each method uses and the sequencing depth. Centrifuge uses a read mapping approach, while Kraken2 uses a k-mer-based system to classify the sequencing reads into taxonomic groups. In conclusion, both Centrifuge and Kraken2 are effective tools for microbial classification. However, the choice of classifier can influence the accuracy of microbial classification and, therefore, should be made carefully, depending on the desired application, even when the same reference database is used.

Long non-coding RNA (lncRNA) participates in various biological processes, however, neither the expression profile nor the biological role of lncRNAs in mammalian ovaries has been fully studied. In this work, the lncRNA transcriptomic analysis of postnatal mice ovaries was performed by using bulk RNA sequencing in C57BL/6 mice. A total of 5302 lncRNAs were found in mouse ovaries, and 1836 lncRNAs were differentially expressed during the development and ageing process, of which targets were enriched in the developmental process, reproduction, etc. Developmental stage specific lncRNAs showed functions in system development, inflammatory response, myeloid leukocyte activation, etc. Moreover, a co-expression network analysis based on reproduction-related genes reveals lncRNAs that may regulate multiple mRNA targets in ovaries, including Neat1, Gm11613 and Gm43915. Two cis-acting lncRNAs, Ptgs2os and Gm14705, showed correlated expression pattern with their potential targets Ptgs2 and Aff2 respectively, and these lncRNA-mRNA pairs were conserved in mice and humans. WGCNA further identified 10 co-expressed modules with distinct expression patterns associated with ovarian development and ageing. Taken together, our results reveal a transcriptomic profile of mouse ovaries over the reproductive lifespan, providing insights into the molecular mechanisms of ovarian development and ageing.

We report the clinical and genetic features of three adult patients with congenital heart disease-associated pulmonary arterial hypertension (CHD-PAH) carrying rare T-box variants. All three patients had weakness and cyanosis. Two patients had chest tightness, dry cough, and hemoptysis, and one patient had lower limb edema. Besides meeting the diagnostic criteria of CHD-PAH, three patients respectively presented the clinical features of specific syndromes. Specifically, patient 1 presented with clinical features consistent with tetralogy of Fallot, patient 2 presented with characteristics associated with small patella syndrome, and the patient 3 exhibited features consistent with Holt-Oram syndrome. Exome sequencing revealed that the TBX1 (c.820 T > C) variant was identified in patient 1, the TBX4 (c.251del) variant was detected in patient 2 and the TBX5 (c.486del) variant was found in patient 3. Our study for the first time found that CHD-PAH patients carry T-box gene variants, which has added new clues to understanding the pathogenesis of CHD-PAH and is expected to provide new targets and ideas for the diagnosis and treatment of CHD-PAH.

Epidermolysis bullosa (EB) is a group of inherited skin disorders characterized by skin fragility and blistering. Here, four Bleu du Maine lambs, sired by one ram, were diagnosed with EB very early in life. Due to the severity of the clinical signs, the lambs had to be euthanized. The affected lambs exhibited hoof sloughing and multiple ulcerations on the head, oral cavity, skin over the joints, and the ruminal pillars. Histopathology showed abrupt subepidermal clefts, epidermal detachment directly above the basal membrane, and ulcerations consistent with junctional EB (JEB). Two cases underwent whole-genome sequencing (WGS) to identify the genetic cause. Genomic analyses with the hypothesis of autosomal recessive inheritance identified the most likely pathogenic homozygous 1-bp deletion in the LAMB3 gene (NC_056065.1:g.73166198delG). Recessive forms of JEB in humans and dogs are caused by variants in LAMB3 gene, which encodes β3 subunit of laminin 332, a critical component of the epidermal basal membrane. The ovine frameshift variant putatively introduces a premature stop codon and disrupts the donor splice site of exon 20. The variant allele was homozygous in both sequenced cases and heterozygous in three unaffected close relatives and was absent in 1075 unrelated control sheep of various other breeds. This study highlights the importance of genetic investigation in veterinary diagnostics of and represents the first report of a LAMB3-related recessive EB in sheep. The findings enable genetic testing to inform breeding strategies and provide a second spontaneous large animal model for LAMB3-related JEB in humans.

Drought stress can damage crop growth and lead to a decline in yield, thereby affecting food security, especially in regions vulnerable to climate change. SNAC1 (stress-responsive NAC1), the NAC transcription factor family member, plays a crucial role in stomatal movement regulation. Effective regulation of stomatal movement is essential for protecting plants from water loss during adverse conditions. Our hypothesis revolves around altering HvSNAC1 activity by introducing a point mutation in its encoding gene, thereby influencing stomatal dynamics in barley. Two TILLING mutants, each harboring missense mutations in the NAC domain, exhibited higher stomatal density after drought stress compared to the parent cultivar 'Sebastian'. These mutants also demonstrated distinct patterns of ABA-induced stomatal movement compared to the wild-type (WT). To delve deeper, we conducted a comprehensive analysis of the transcriptomes of these mutants and the parent cultivar 'Sebastian' under both optimal watering conditions and 10 days of drought stress treatment. We identified differentially expressed genes (DEGs) between the mutants and WT plants under control and drought conditions. Furthermore, we pinpointed DEGs specifically expressed in both mutants under drought conditions. Our experiments revealed that the cis-regulatory motif CACG, previously identified in Arabidopsis and rice, is recognized by HvSNAC1 in vitro. Enrichment analysis led to the identification of the cell wall organization category and potential target genes, such as HvEXPA8 (expansin 8), HvXTH (xyloglucan endotransglucosylase/hydrolase), and HvPAE9 (pectin acetylesterase 9), suggesting their regulation by HvSNAC1. These findings suggest that HvSNAC1 may play a role in regulating genes associated with stomatal density, size and reopening.

The Caracu is a taurine breed adapted to Brazil's climatic conditions and has been selected for 40 + years for Body Weight (BW), maintaining performance records across multiple generations in its database. However, selecting young animals for BW can result in excessive growth, potentially impacting carcass and reproductive traits. This study aimed to estimate genetic correlations and, based on these estimates, evaluate how selection for BW (adjusted to 378 and 550 days of age for males and females, respectively) has influenced carcass traits and reproductive efficiency in this breed. The dataset contained records for BW (kg), Ribeye area (REA, cm²), Height-to-width ratio of the Longissimus dorsi muscle (HWR), Backfat thickness (BFT, mm), Rump fat thickness (RFT, mm), Yearly scrotal circumference (SC, cm), and Days to calving (DC, days) from animals born between 1966 and 2022. (Co)variance components were estimated by Bayesian inference using two-trait animal models. Analyses were conducted to estimate genetic parameters for pairs of traits, including BW with carcass traits (BW × REA, BW × HWR, BW × BFT, and BW × RFT) and BW with reproductive traits (BW × DC and BW × SC). Additionally, analyses were performed for pairwise combinations among carcass traits (REA × HWR, REA × BFT, REA × RFT, HWR × BFT, HWR × RFT, and RFT × BFT) and between reproductive traits (DC × SC). The relationship matrix included 4,783 animals, of which 829 were genotyped with the GGP Bovine 100 K SNP panel. Favorable genetic correlations (r_g) were observed between BW and REA (0.51 ± 0.11), HWR (0.45 ± 0.17), SC (0.24 ± 0.13), and RFT (0.15 ± 0.21), with the latter being favorable but low. On the other hand, unfavorable genetic correlations were observed between BW and BFT (-0.07 ± 0.21), which was unfavorable but close to zero relationship, and between BW and DC (0.48 ± 0.15). The significance of carcass and reproductive traits is underscored by the favorable, r_g between BW and the carcass traits REA (BW × REA) and HWR (BW × HWR), while a high, unfavorable r_g was observed between BW and DC cows. These findings emphasize the importance of carefully balancing genetic selection to optimize growth, carcass quality, and adequate reproduction in Caracu cattle.

The progressive degradation of the renal parenchyma and reduction of functional nephrons characterise chronic kidney disease (CKD). Disorders of bone mineral metabolism is one of the leading causes of morbidity and mortality in CKD. Calcium-sensing receptor (CASR) allows cells to detect changes in blood calcium levels and regulate its concentration. Hence, we aim to study the relationship between genetic variants of CASR and CKD and their relation with mineral bone disease (MBD). A total of 180 CKD patients and 180 controls were recruited. Bone mineral density of the lumbar spine, hip, and forearm was measured using a dual X-ray absorptiometry (DEXA) scan. Circulating levels of parathyroid hormone (PTH) were measured by ELISA. Genotyping was done by real-time quantitative PCR. A significant difference in the distribution of the GAG haplotype (rs7652589, rs1501899, rs1801725) was observed between CKD patients and controls. Participants with the GT genotype of rs1801725 had lower BMD in the forearm. The TT genotype of rs1801725 was associated with decreased serum calcium levels. A regression model indicated that the GT genotype of rs1801725 and AG and GG genotypes of rs7652589 were significant predictors of forearm BMD. GAG haplotype of CASR SNPs is linked to CKD risk in South Indian Tamils. GT genotype of rs1801725 and AG and GG genotype of rs7652589 are independent predictors of MBD in patients with CKD.