Genes最新文献

Background: Genomic analysis is crucial for better understanding the evolutionary history of species and for their conservation. Shizhenia pinguicula is a rare medicinal plant endemic to China. However, the complete chloroplast genome of this species has not been reported to date. Insufficient genomic research on S. pinguicula has hindered effective conservation efforts for this valuable plant.

Methods: In this study, we sequenced and assembled the first complete chloroplast genome of S. pinguicula using Illumina sequencing technology. We conducted a comparative analysis of its chloroplast genome with related species and reconstructed phylogenetic relationships.

Results: The chloroplast genome of S. pinguicula exhibited a typical quadripartite structure with a length of 158,658 bp. A total of 123 genes, 118 simple sequence repeats, and 51 dispersed repetitive sequences were identified. The inverted repeat boundaries were significantly expanded, along with the pseudogenization and loss of multiple NDH genes. Codon usage bias is primarily influenced by natural selection and other factors, with the ycf3 gene under positive selection. Additionally, 10 hypervariable regions were detected for species identification and evolutionary studies. Phylogenetic analysis indicated that Ponerorchis gracilis and Hemipilia yajiangensis form a clade, with S. pinguicula as their sister species, located at the basal position of the Ponerorchis-Hemipilia alliance.

Conclusions: The chloroplast genome structure and gene content of S. pinguicula exhibit certain degrees of variation compared to other species within the Orchidinae subtribe. This genome should be useful for further investigations into the biology of Shizhenia and the development of biodiversity conservation strategies.

Improving the efficiency of germplasm innovation has always been the aim of rice breeders. Traditional hybrid breeding methods for variety selection rarely meet the practical needs of rice production. The emergence of genome-editing technologies, such as CRISPR/Cas9, provides a new approach to the genetic improvement of crops such as rice. The number of published scientific papers related to "gene editing" and "CRISPR/Cas9" retrievable on websites both from China and other countries exhibited an increasing trend, year by year, from 2014 to 2023. Research related to gene editing in rice accounts for 33.4% and 12.3% of all the literature on gene editing published in China and other countries, respectively, much higher than that on maize and wheat. This article reviews recent research on CRISPR/Cas9 gene-editing technology in rice, especially germplasm innovation and genetic improvement of commercially promoted varieties with improved traits such as disease, insect, and herbicide resistance, salt tolerance, quality, nutrition, and safety. The aim is to provide a reference for the precise and efficient development of new rice cultivars that meet market demand.

Background: Multiple epiphyseal dysplasia (MED) is a clinically and genetically heterogeneous group of skeletal diseases characterized by epiphyseal abnormalities associated with mild short stature. The clinical variability is wide, and the first clinical manifestations still occur in childhood with joint pain and stiffness that evolve into degenerative joint disease. MED, caused by mutations in the Cartilage Oligomeric Matrix Protein (COMP) gene, is the most common form of the disease. COMP-MED usually shows significant involvement of the capital femoral epiphyses and irregular acetabulum; instead, COL9A1-, COL9A2-, and COL9A3-MED appear to have more severe knee involvement than hips, resulting in a milder presentation than COMP-MED cases. Other complications have been reported, in particular osteochondritis dissecans (OCD), which has been described in two large COL9A2-related MED families associated with myopathy.

Methods: Here, we report the case of a 24-year-old man affected by COMP-MED with a positive family history for the disease and a clinical presentation that interestingly is characterized by the presence of multiple OCD.

Results: To our knowledge, this is the first case of COMP mutations related to multiple OCD as the main clinical feature.

Conclusions: This report can expand the clinical phenotype related to the pathogenic variants of the COMP gene, as it shows that multiple OCD can also be present in COMP-related MED as well as in COL9A2-related MED.

Background/objectives: Antisense oligonucleotide (ASO)-mediated exon-skipping is an effective approach to restore the disrupted reading frame of the dystrophin gene for the treatment of Duchenne muscular dystrophy (DMD). Currently, four FDA-approved ASOs can target three different exons, but these therapies are mutation-specific and only benefit a subset of patients. Understanding the broad applicability of exon-skipping approaches is essential for prioritizing the development of additional therapies with the greatest potential impact on the DMD population. This review offers an updated analysis of all theoretical exon-skipping strategies and their applicability across the patient population, with a specific focus on DMD-associated mutations documented in the UMD-DMD database. Unlike previous studies, this approach leverages the inclusion of phenotypic data for each mutation, providing a more comprehensive and clinically relevant perspective.

Methods: The theoretical applicability of all single and double exon-skipping strategies, along with multi exon-skipping strategies targeting exons 3-9 and 45-55, was evaluated for all DMD mutations reported in the UMD-DMD database.

Results: Single and double exon-skipping approaches were applicable for 92.8% of large deletions, 93.7% of small lesions, 72.4% of duplications, and 90.3% of all mutations analyzed. Exon 51 was the most relevant target and was applicable for 10.6% of all mutations and 17.2% of large deletions. Additionally, two multi-exon-skipping approaches, targeting exons 45-55 and 3-9, were relevant for 70.6% of large deletions and 19.2% of small lesions.

Conclusions: Current FDA-approved ASOs were applicable to 27% of the UMD-DMD population analyzed, leaving a significant portion of patients without access to exon-skipping therapies. The clinical translation of alternative approaches is critical to expanding the accessibility of these therapies for the DMD population.

Background/Objectives:MIR27A rs895819 polymorphism has emerged as a potential additional pharmacogenomic marker of fluoropyrimidine response. Current evidence on its potential effect on miR-27a expression, which represses DPD activity, leading to DPD deficiency and increased fluoropyrimidine-associated toxicity risk, is scarce and inconsistent. We have analyzed the effect of MIR27A rs895819 polymorphism on miR-27a-3p plasma expression levels under different models of inheritance to contribute further evidence on its plausible biological role in miR-27a expression. Methods: A total of 59 individuals with no medical history of cancer were included in this study. MIR27A rs895819 genotyping and miR-27a-3p expression were analyzed by using predesigned TaqMan assays. Results: The frequency of TT, TC, and CC genotypes was present at a prevalence of 50.8%, 44.1%, and 5.1%, respectively. Individuals carrying the CC genotype presented with decreased miR-27a-3p expression (0.422 fold-change versus TT, p = 0.041; 0.461 fold-change versus TC, p = 0.064), whereas no differences were present between TT and TC individuals (1.092 fold-change, p = 0.718). miR-27a-3p expression was decreased in CC individuals under a recessive model of inheritance (0.440 fold-change, p = 0.047). No differences were found in dominant (TT vs. TC+CC, 0.845 fold-change, p = 0.471) or over dominant (TT+CC vs. TC, 0.990 fold-change, p = 0.996) models of inheritance. Conclusions:MIR27A rs895819CC genotype leads to severely reduced miR-27a-3p expression in plasma. Further study of this association is warranted in cancer patients to apply MIR27A genotyping in therapeutics to identify fluoropyrimidine-treated patients who are at a decreased risk of experiencing fluoropyrimidine-induced severe toxicity.

Background: Autosomal recessive inherited pathogenetic variants in the histidine triad nucleotide-binding protein 1 (HINT1) gene are responsible for an axonal Charcot-Marie-Tooth neuropathy associated with neuromyotonia, a phenomenon resulting from peripheral nerve hyperexcitability that causes a spontaneous muscle activity such as persistent muscle contraction, impaired relaxation and myokymias.

Methods: Herein, we describe two brothers in whom biallelic HINT1 variants were identified following a multidisciplinary approach.

Results: The younger brother came to our attention for clinical evaluation of moderate intellectual disability, language developmental delay, and some behavioral issues. His elder brother presented mild intellectual disability, hyperactivity, tiptoe walking, and gait ataxia. At first evaluation, motor impairment with frequent falls, pes cavus, and distal hyposthenia with reduced osteotendinous reflexes were found in both. Grip myotonic phenomenon was also noted. Blood tests revealed mildly elevated creatine kinase, and neurophysiology investigations revealed predominantly axonal polyneuropathy. Muscle MRI highlighted fibro-adipose infiltration, prevalent in the lower limbs. Gene panel testing detected a heterozygous HINT1 variant (c.355C>T/p.(Arg119Trp)) on the paternal allele. A further in-depth analysis using Integrative Genomics Viewer and Optical Genome Mapping led us to identify an additional variant in HINT1 represented by a complex rearrangement located in the region 5'UTR-exon 1-intron 1, not previously described.

Conclusions: This complex rearrangement could have been overlooked if the clinical picture had not been evaluated as a whole (from a clinical, neurophysiological, and neuroimaging point of view). Neuropsychiatric manifestations (intellectual disability, hyperactivity, etc.) are part of the picture of HINT1-related neuromyotonia.

Background/objectives: Aneuploidy is a prevalent cancer feature that occurs in many solid tumors. For example, high-grade serous ovarian cancer shows a high level of copy number alterations and genomic rearrangements. This makes genomic variants appealing as diagnostic or prognostic biomarkers, as well as for their easy detection. In this study, we focused on copy number (CN) losses shared by ovarian cancer stem cells (CSCs) to identify chromosomal regions that may be important for CSC features and, in turn, for patients' prognosis.

Methods: Array-CGH and bioinformatic analyses on three CSCs subpopulations were performed.

Results: Pathway and gene ontology analyses on genes involved in copy number loss in all CSCs revealed a significant decrease in mRNA surveillance pathway, as well as miRNA-mediated gene silencing. Then, starting from these CN losses, we validated their potential prognostic relevance by analyzing the TCGA cohort. Notably, losses of 4q34.3-q35.2, 8p21.2-p21.1, and 18q12.2-q23 were linked to increased genomic instability. Loss of 18q12.2-q23 was also related to a higher tumor stage and poor prognosis. Finally, specific genes mapping in these regions, such as PPP2R2A and TPGS2A, emerged as potential biomarkers.

Conclusions: Our findings highlight the importance of genomic alterations in ovarian cancer and their impact on tumor progression and patients' prognosis, offering advance in understanding of the application of numerical aberrations as prognostic ovarian cancer biomarkers.

Background: Zingiber Mill., a morphologically diverse herbaceous perennial genus of Zingiberaceae, is distributed mainly in tropical to warm-temperate Asia. In China, species of Zingiber have crucial medicinal, edible, and horticultural values; however, their phylogenetic relationships remain unclear.

Methods: To address this issue, the complete plastomes of the 29 Zingiber accessions were assembled and characterized. Comparative plastome analysis and phylogenetic analysis were conducted to develop genomic resources and elucidate the intraspecific phylogeny of Zingiber.

Results: The newly reported plastomes ranged from 161,495 to 163,880 bp in length with highly conserved structure. Results of comparative analysis suggested that IR expansions/contractions and changes of repeats were the main reasons that influenced the genome size of the Zingiber plastome. A large number of SSRs and six highly variable regions (rpl20, clpP, ycf1, petA-psbJ, rbcL-accD, and rpl32-trnL) have been identified, which could serve as potential DNA markers for future population genetics or phylogeographic studies on this genus. The well-resolved plastome phylogeny suggested that Zingiber could be divided into three clades, corresponding to sect. Pleuranthesis (sect. Zingiber + sect. Dymczewiczia) and sect. Cryptanthium.

Conclusions: Overall, this study provided a robust phylogeny of Zingiber plants in China, and the newly reported plastome data and plastome-derived markers will be of great significance for the accurate identification, protection, and agricultural management of Zingiber resources in the future.

Background: Calgranulin B (S100A9) was found to be strongly associated with milk protein percentage in dairy cattle in our previous genome-wide association study.

Methods: SNPs in S100A9 were identified via pooled sequencing, and genotyping of 1054 cows was performed individually using MassArray with MALDI-TOFMS technology. Association analyses between the S100A9 SNPs and five milk production traits were conducted using SAS 9.2 software. Functional studies of S100A9 were conducted using quantitative PCR, Western blot, CCK-8, and immunofluorescence assays.

Results: In the present study, we further verified that two SNPs in S100A9, g.17115387 C>A and g.17115176 C>A, were significantly associated with milk protein percentage. We found that S100A9 could affect the expressions of caseins CSN1S1, CSN2, and CSN3 in MAC-T cells by regulating the expressions of amino acid transporter genes. We investigated the effects of S100A9 on the PI3K-Akt, WNT, and mTOR pathways, which are well known to play important roles in mammary gland development and milk protein synthesis. Our results suggest that S100A9 regulates the expressions of the relevant genes in these pathways, and thus potentially influences the protein synthesis in the mammary gland.

Conclusions: This study demonstrates the important role of the S100A9 gene in the milk protein trait of dairy cattle and provides new insights into the molecular mechanism of milk protein content.

The SNP variation in sockeye salmon across the Asian part of its range was studied in 23 samples from 16 lake-river systems of the West Pacific Coast to improve understanding of genetic adaptation in response to spawning watersheds conditions. Identification of candidate SNPs and environmental factors that can contribute to local adaptations in sockeye salmon populations was carried out using redundancy analysis (RDA), a powerful tool for landscape genetics proven to be effective in genotype-environment association studies. Climatic and hydrographic indices (7 indices in total), reflecting abiotic conditions in freshwater habitats of sockeye salmon and characterizing the temperature regime in the river basin, its variability during the year, the amount of precipitation, as well as the height of the maximum tide in the estuary, were used as predictor factors. Among the 45 analyzed SNPs, several loci (ALDOB-135, HGFA, and RAG3-93) correlated with predictors gradients along the northwest Pacific coast were identified. The putative candidate loci localized in genes involved in the immune and inflammatory responses, as well as genes encoding temperature-sensitive enzymes and some hormones regulating ion homeostasis in fish during the anadromous migration and smoltification, were potentially associated with environmental conditions in natal rivers. The findings could have implications for aquaculture, conservation, and resource management in the context of global climate change.