Journal of Genetics and Genomics最新文献

When plants respond to drought stress, dynamic cellular changes occur, accompanied by alterations in gene expression, which often act through trans-regulation. However, the detection of trans-acting genetic variants and networks of genes is challenged by the large number of genes and markers. Using a tensor decomposition method, we identify trans-acting expression quantitative trait loci (trans-eQTLs) linked to gene modules, rather than individual genes, which were associated with maize drought response. Module-to-trait association analysis demonstrates that half of the modules are relevant to drought-related traits. Genome-wide association studies of the expression patterns of each module identify 286 trans-eQTLs linked to drought-responsive modules, the majority of which cannot be detected based on individual gene expression. Notably, the trans-eQTLs located in the regions selected during maize improvement tend towards relatively strong selection. We further prioritize the genes that affect the transcriptional regulation of multiple genes in trans, as exemplified by two transcription factor genes. Our analyses highlight that multidimensional reduction could facilitate the identification of trans-acting variations in gene expression in response to dynamic environments and serve as a promising technique for high-order data processing in future crop breeding.

Fungi are a diverse kingdom characterized by remarkable genomic plasticity that facilitates pathogenicity and adaptation to adverse environmental conditions. In this review, we delve into the dynamic organization of fungal genomes and its implications for host adaptation and antifungal resistance. We examine key features and the heterogeneity of genomes across different fungal species, including but not limited to their chromosome content, DNA composition, distribution and arrangement of their content across chromosomes, and other major traits. We further highlight how this variability in genomic traits influences their virulence and adaptation to adverse conditions. Fungal genomes exhibit large variations in size, gene content, and structural features, such as abundance of transposable elements (TEs), compartmentalization into gene-rich and TE-rich regions, and the presence or absence of dispensable chromosomes. Genomic structural variations are equally diverse in fungi, ranging from whole-chromosome duplications that may enhance tolerance to antifungal compounds, to targeted deletion of effector encoding genes that may promote virulence. Finally, the often-overlooked fungal mitochondrial genomes can also affect virulence and resistance to fungicides. Such and other features of fungal genome organization are reviewed and discussed in the context of host-microbe interactions and antifungal resistance.

Nitrogen (N) is vital for crop growth and yield, impacting food quality. However, excessive use of N fertilizers leads to high agricultural costs and environmental challenges. This review offers a thorough synthesis of the genetic and molecular regulation of N uptake, assimilation, and remobilization in maize, emphasizing the role of key genes and metabolic pathways in enhancing N use efficiency (NUE). We summarize the genetic regulators of N transports for nitrate (NO₃^-) and ammonium (NH₄⁺) that contribute to efficient N uptake and transportation. We further discuss the molecular mechanisms by which root system development adapts to N distribution and how N influences root system development and growth. Given the advancements in high-throughput microbiome studies, we delve into the impact of rhizosphere microorganisms on NUE and the complex plant-microbe interactions that regulate maize NUE. Additionally, we conclude with intricate regulatory mechanisms of N assimilation and remobilization in maize, involving key enzymes, transcription factors, and amino acid transporters. We also scrutinize the known N signaling perception and transduction mechanisms in maize. This review underscores the challenges in improving maize NUE and advocates for an integrative research approach that leverages genetic diversity and synthetic biology, paving the way for sustainable agriculture.

Accumulation of mutant proteins in cells can induce proteinopathies and cause functional damage to organs. Recently, the Cingulin (CGN) protein has been shown to maintain the morphology of cuticular plates of inner ear hair cells and a frameshift mutation in CGN causes autosomal dominant non-syndromic hearing loss. Here, we find that the mutant CGN proteins form insoluble aggregates which accumulate intracellularly and lead to cell death. Expression of the mutant CGN in the inner ear results in severe hair cell death and hearing loss in mice, resembling the auditory phenotype in human patients. Interestingly, a human-specific residue (V1112) in the neopeptide generated by the frameshift mutation is critical for the aggregation and cytotoxicity of the mutant human CGN. Moreover, the expression of heat shock factor 1 (HSF1) decreases the accumulation of insoluble mutant CGN aggregates and rescues cell death. In summary, these findings identify mutant-specific toxic polypeptides as a disease-causing mechanism of the deafness mutation in CGN, which can be targeted by the expression of the cell chaperone response regulator HSF1.

Gene therapy has shown significant potential in treating various diseases, particularly inherited blood disorders such as hemophilia, sickle cell disease, and thalassemia. Advances in understanding the regulatory network of disease-associated genes have led to the identification of additional therapeutic targets for treatment, especially for β-hemoglobinopathies. Erythroid regulatory factor BCL11A offers the most promising therapeutic target for β-hemoglobinopathies, and reduction of its expression using the commercialized gene therapy product Casgevy has been approved for use in the UK and USA in 2023. Notably, the emergence of innovative gene editing technologies has further broadened the gene therapy landscape, presenting possibilities for treatment. Intensive studies indicate that base editing and prime editing, built upon CRISPR technology, enable precise single-base modification in hematopoietic stem cells for addressing inherited blood disorders ex vivo and in vivo. In this review, we present an overview of the current landscape of gene therapies, focusing on clinical research and gene therapy products for inherited blood disorders, evaluation of potential gene targets, and the gene editing tools employed in current gene therapy practices, which provides an insight for the establishment of safer and more effective gene therapy methods for a wider range of diseases in the future.

Human UDP-glycosyltransferases (UGTs) are responsible for the glycosylation of a wide variety of endogenous substrates and commonly prescribed drugs. Different genetic polymorphisms in UGT genes are implicated in interindividual differences in drug response and cancer risk. However, the genetic complexity beyond these variants has not been comprehensively assessed. We here leveraged whole-exome and whole-genome sequencing data from 141,456 unrelated individuals across 7 major human populations to provide a comprehensive profile of genetic variability across the human UGT gene family. Overall, 9666 exonic variants were observed, of which 98.9% were rare. To interpret the functional impact of UGT missense variants, we developed a gene family-specific variant effect predictor. This algorithm identified a total of 1208 deleterious variants, most of which were found in African and South Asian populations. Structural analysis corroborated the predicted effects for multiple variations in substrate binding sites. Combined, our analyses provide a systematic overview of UGT variability, which can yield insights into interindividual differences in phase 2 metabolism and facilitate the translation of sequencing data into personalized predictions of UGT substrate disposition.