Genes最新文献

The Notch signaling pathway plays a major role in embryological development and in the ongoing life processes of many animals. Its role is to provide cell-to-cell communication in which a Sender cell, bearing membrane-embedded ligands, instructs a Receiver cell, bearing membrane-embedded receptors, to adopt one of two available fates. Elucidating the evolution of this pathway is the topic of this paper, which uses an orthologs approach, providing a comprehensive basis for the study. Using BLAST searches, orthologs were identified for all the 49 components of the Notch signaling pathway. The historical time course of integration of these proteins, as the animals evolved, was elucidated. Insofar as cell-to-cell communication is of relevance only in multicellular animals, it is not surprising that the Notch system became functional only with the evolutionary appearance of Metazoa, the first multicellular animals. Porifera contributed a quarter of the Notch pathway proteins, the Cnidaria brought the total to one-half, but the system reached completion only when humans appeared. A literature search elucidated the roles of the Notch system's components in modern descendants of the ortholog-contributing ancestors. A single protein, the protein tyrosine kinase (PTK) of the protozoan Ministeria vibrans, was identified as a possible pre-Metazoan ancestor of all three of the Notch pathway proteins, DLL, JAG, and NOTCH. A scenario for the evolution of the Notch signaling pathway is presented and described as the co-option of its components, clade by clade, in a repurposing of genes already present in ancestral unicellular organisms.

(1) Background: Buffaloes are crucial livestock species for food and service in tropical and subtropical regions. Buffalo genetics, particularly in indigenous Chinese breeds such as the Xiangxi white buffalo (XWB), remains an intriguing area of study due to its unique traits and regional significance. (2) Methods: This investigation utilized the whole-genome sequences of twenty XWBs (newly sequenced), along with eighty published whole-genome sequences of other buffalo breeds (including Guizhou white buffalo, river buffalo, and Chinese buffalo in the Yangtze River). Using whole-genome sequencing analysis technology, the population structure, genomic diversity, and selection signatures of XWB were determined. (3) Results: This study revealed that the XWB, being phylogenetically positioned in the middle and lower reaches of the Yangtze River, exhibited substantial genomic diversity. Employing four selection sweep detection methods (CLR, iHS, π-ratio, and F_ST), several genes were positively identified for adaptive traits in the XWB, including coat color phenotypes (ASIP, KIT), the nervous system (GRIK2), reproduction (KCNIP4), growth and development (IFNAR1, BMP6, HDAC9, MGAT4C, and SLC30A9), the body (LINGO2, LYN, and FLI1), immunity (IRAK3 and MZB1), and lactation (TP63, LPIN1, SAE1). (4) Conclusions: In conclusion, this study enhances our understanding of the genetic distinctiveness and adaptive traits of XWB, highlighting selection signatures crucial for future breeding and conservation and ensuring sustainable use of this vital livestock resource.

Background/objectives: Hearing loss (HL) is a significant global health concern, affecting approximately 1 in every 1000 newborns, with over half of these cases attributed to genetic factors. This study focuses on identifying the genetic basis of autosomal recessive non-syndromic hearing loss (ARNSHL) in a consanguineous Emirati family.

Methods: Clinical exome sequencing (CES) was performed on affected members of the family, followed by Sanger sequencing to validate the findings. Specific primers were used for PCR amplification of target CDH23 exons. Mutations were analyzed using various computational tools to assess their pathogenicity.

Results: We identified two heterozygous mutations in the CDH23 gene: a novel nonsense variant (c.264G>A, p.Trp88Ter) and a missense variant (c.5168G>A, p.Arg1723His). Both mutations were found in trans configuration, suggesting a compound heterozygous state contributing to the phenotype. In silico analysis predicted a significant impact on protein function, potentially leading to the observed ARNSHL.

Conclusions: This study emphasizes the complexity of genetic factors in hearing loss, particularly in highly consanguineous populations. The identification of both nonsense and missense mutations in the CDH23 gene enhances understanding of its role in hearing loss and provides essential insights for genetic counseling and future therapeutic strategies.

Background: MYH6 variants are the most well-known genetic risk factor (10%) for hypoplastic left heart syndrome (HLHS) and are associated with decreased cardiac transplant-free survival. MYH6 encodes for α-myosin heavy chain (α-MHC), a contractile protein expressed in the neonatal atria. We therefore assessed atrial function in HLHS patients with MYH6 variants. Methods: We performed a retrospective, blinded assessment of pre-stage I atrial function using 2D speckle-tracking echocardiography (2D-STE). Variant carriers were control-matched based on AV valve anatomy, sex, and birth year. Studies were obtained postnatally from awake patients prior to surgical intervention. Right atrial (RA) and right ventricular (RV) strain and strain rate (SR) were measured from the apical four-chamber view. Results: A total of 19 HLHS patients with MYH6 variants had echocardiograms available; 18 were matched to two controls each, and one had a single control. RA active strain (ASct) was decreased in variant carriers (-1.41%, IQR -2.13, -0.25) vs. controls (-3.53%, IQR -5.53, -1.28; p = 0.008). No significant differences were identified in RV strain between the groups. RA reservoir strain (ASr) and conduit strain (AScd) positively correlated with heart rate (HR) in MYH6 variant carriers only (ASr R = 0.499, p = 0.029; AScd R = 0.469, p = 0.043). RV global longitudinal strain (GLS) as well as RV systolic strain (VSs) and strain rate (VSRs) correlated with HR in controls only (GLS R = 0.325, p = 0.050; VSs R = 0.419, p = 0.010; VSRs R = 0.410, p = 0.012). Conclusions: We identified functional consequences associated with MYH6 variants, a known risk factor for poor outcomes in HLHS. MYH6 variant carriers exhibit impaired RA contractility despite there being no differences in RV function between variant carriers and controls. MYH6 variants are also associated with an ineffective RA reservoir and conduit function at high heart rates, despite preserved RV diastolic function. RA dysfunction and reduced atrial "kick" may therefore be a significant contributor to RV failure and worse clinical outcomes in HLHS patients with MYH6 variants.

Background: Tulipa species are economically, culturally, scientifically, and ecologically important. Tulips present taxonomic complexities that cannot be adequately resolved by examining their morphological characteristics alone or by relying on a limited selection of genetic markers.

Methods: In the present study, we assessed the complete plastid sequences of Tulipa alberti Regel and Tulipa greigii Regel collected from Kazakhstan. Additionally, 14 previously published plastomes were obtained from GenBank for comparison and phylogenetic analysis.

Results: The plastid genome sizes of T. alberti and T. greigii were 152,359 bp and 152,242 bp, respectively. In the plastid genomes of T. alberti and T. greigii, 136 genes were annotated, 114 of which were unique. These unique genes comprised eighty protein-coding, thirty transfer RNA, and four ribosomal RNA genes. Additionally, 415 simple sequence repeats were identified, comprising 107 tandem, 40 forward, 49 palindromic, 8 reverse, and 1 complementary repeat. Notably, the region containing ycf1 exhibited high variability and may serve as an informative DNA barcode for this genus.

Conclusion: Phylogenetic analysis showed strong support for the relationships among Tulipa species, indicating the utility of plastid genome data for further taxonomic studies within the genus.

Background: Tissue regenerative capacity following evisceration, potentially influenced by environmental contaminants and intestinal microflora, is essential for the financial success of Apostichopus japonicus farming. However, the morphological structure, gut microbiome composition, and genes expression pattern of the regenerated gut after exposure to high levels of TBBPA remain poorly unclear.

Methods: In this research, the effect of TBBPA exposure on tissue regeneration in A. japonicus was investigated through a comprehensive multi-omics approach.

Results: Our results showed that the integrity, the intestinal wall thickness, and the villi length of the regenerated intestines in A. japonicus decreased after treatment with high levels of TBBPA. The findings from PCoA and NMDS analyses revealed that the microbial community composition was significantly altered following exposure to high concentrations of TBBPA in the regenerated intestines of A. japonicus. The KEGG pathway enrichment analysis indicated that the DEGs (differentially expressed genes) were predominantly enriched on metabolism and immunity-related signaling pathways after exposure to high levels of TBBPA. These included pathways involved in the PPAR signaling pathway, ECM receptor interaction, glycerolipid metabolism, and fatty acid degradation. Interestingly, the results have demonstrated that there are 77 transcript factors that were significantly different after exposure to TBBPA.

Conclusions: These results suggested that high levels of exposure to TBBPA induces an imbalance of the metabolic homeostasis by regulating the expression levels of transcription factors in the regenerated intestines of A. japonicus.

Background/objectives: Teosinte branched1/Cycloidea/Proliferating cell nuclear antigen factors (TCPs) are plant-specific transcription factors involved in leaf development, flowering, branching, hormone signaling, and stress responses. Prunus a key temperate fruit tree with ornamental spring blooms, still lacks comprehensive TCP gene studies across many species.

Methods: We identified 154 TCP genes in eight Prunus species: 19 in Prunus tenella var. tenella, 19 in P. amygdalus, 17 in P. armeniaca 'Rojo Pasion', 19 in P. mira, 20 in P. jamasakura var. jamasakura, 19 in P. fruticosa, 19 in P. mume var. tortuosa, and 22 in P. × yedoensis 'Somei-yoshino'. These genes were classified into PCF, CIN, and CYC/TB1 groups. We examined segmental duplication, conserved motifs, and cis-acting elements. Expression patterns of 12 TCPs in P. tenella var. tenella were tested under low-temperature stress (25 °C, 5 °C, -5 °C, and -10 °C), and PtTCP9's subcellular localization was determined.

Results: TCP genes within the same groups showed similar motifs and cis-acting elements. Cold stress analysis identified multiple low-temperature-responsive elements in gene promoters. Four genes (PtTCP2, PtTCP6, PtTCP14, and PtTCP16) increased expression under cold stress, while six genes (PtTCP1, PtTCP5, PtTCP8, PtTCP9, PtTCP17, and PtTCP19) decreased. PtTCP9 was localized to the nucleus.

Conclusions: This was the first genome-wide study of the TCP gene family in these eight Prunus species, providing valuable insights into the characteristics and functions of TCP genes within this important genus.

Background/Objectives: CD161, encoded by the KLRB1 gene, is an inhibitory receptor expresses on various immune cell and has gained attention in immune checkpoint research. In recent studies, KLRB1 has been found to be one of the potential markers of liver diseases such as cirrhosis. Therefore, it will be important to understand what process KLRB1 involved in the liver for the prevention of liver diseases. Methods: We compared KO mice with wild-type controls by routine blood analysis and RNA-seq, and additionally performed H&E staining and qPCR to validate the differentially expressed genes (DEGs). Results:KO mice had fewer lymphocytes compared to the wild-type mice. A transcriptomic analysis showed that Klrb1 loss causes the upregulation of immune-related genes and pathways like NOD-like receptor and p53 signaling, while causing the downregulation of lipid metabolism-related genes. A protein interaction analysis indicated a potential cancer risk under chronic inflammation. Histological examination with H&E staining reveals an inflammatory response around the central venous vessels in the liver tissue of the KO mice. Conclusions: We conclude that Klrb1 knockout disrupts the immune and metabolic functions in the liver, which may possibly lead to chronic inflammation and malignancy risks. These findings highlight the role of Klrb1 in hepatic health.

Background: Atopic dermatitis (AD) is caused by interactions between genetic susceptibility and environmental factors. Transmembrane protein 232 (TMEM232) is one of the genes strongly implicated in AD. Methods: In the present study, we aimed to investigate the association between AD with variants within TMEM232 based on maternal factors, including a history of allergic diseases, and sensitization to Der f. We performed a candidate gene association study involving the Cohort for Childhood Origins of Asthma and Allergic Diseases. Results: A single variant of the TMEM232 gene, rs17132261, was found to be significantly associated with AD. Subjects carrying the wild-type allele (C) of rs17132261 had higher total IgE than those carrying the variant rs17132261 (T). Multiple logistic regression analysis showed a statistically significant association between TMEM232 gene polymorphism and an increased risk of AD in one-year-old infants. Moreover, rs17132261 was associated with increased total IgE in infants with a maternal history of allergic disease. The group with the CC genotype showed a higher risk of developing AD compared to carriers of CT and TT genotypes when the mother had a history of allergic diseases or was sensitized to Der f. Conclusions: Our findings demonstrate that the TMEM232 risk allele, in combination with maternal factors, higher the total IgE, which could be a potential risk factor for AD.

Background/Objectives: Mitochondria are the main organelles for ATP synthesis able to produce energy for several different cellular activities. Cardiac cells require high amounts of energy and, thus, they contain a high number of mitochondria. Consequently, mitochondrial dysfunction in these cells is a crucial factor for the development of cardiovascular diseases. Mitochondria constitute central regulators of cellular metabolism and energy production, producing approximately 90% of the cells' energy needs in the form of ATP via oxidative phosphorylation. The mitochondria have their own circular, double-stranded DNA encoding 37 genes. Any mitochondrial DNA sequence anomaly may result in defective oxidative phosphorylation and lead to cardiac dysfunction. Methods: In this study, we investigated the potential association between mitochondrial DNA mutation and cardiovascular disease. Cardiac tissue and serum samples were collected from seven patients undergoing coronary artery bypass grafting. Total DNA was extracted from cardiac muscle tissue specimens and serum and each sample was subjected to polymerase chain reaction (PCR) to amplify the NADH dehydrogenase 1 (ND1) gene, which is part of the mitochondrial complex I enzyme complex and was screened for mutations. Results: We identified one patient with a homoplasmic A to G substitution mutation in cardiac tissue DNA and two patients with heteroplasmic A3397G mutation in serum DNA. Specifically, amplicon sequence analysis revealed a homoplasmic A3397G substitution in the ND1 gene in a tissue sample of the patient with ID number 1 and a heteroplasmic mutation in A3397G in serum samples of patients with ID numbers 3 and 6, respectively. The A to G substitution changes the amino acid from methionine (ATA) to valine (GTA) at position 31 of the ND1 gene. Conclusions: The detection of this novel mutation in patients with coronary artery disease may contribute to our understanding of the association between mitochondrial dysfunction and the disease, implying that mitochondria may be key players in the pathogenesis of cardiovascular diseases.