Journal of Genetics and Genomics最新文献

While conventional FISH and IHC methods struggle to decode complex tissue heterogeneity and comprehensive molecular diagnosis due to low-throughput spatial information, spatial omics technologies enable high-throughput molecular mapping across tissue microenvironments. These technologies are emerging as transformative tools in molecular diagnostics and medical research. By integrating histopathological morphology with spatial multi-omics profiling (genome, transcriptome, epigenome, and proteome), spatial omics technologies open an avenue for understanding disease progression, therapeutic resistance mechanisms, and precise diagnosis. It particularly enhances tumor microenvironment analysis by mapping immune cell distributions and functional states, which may greatly facilitate tumor molecular subtyping, prognostic assessment, and prediction of the radiotherapy and chemotherapy efficacy. Despite the substantial advancements in spatial omics, the translation of spatial omics into clinical applications remains challenging due to robustness, efficacy, clinical validation, and cost constraints. In this review, we summarize the current progress and prospects of spatial omics technologies, particularly in medical research and diagnostic applications.

Body size control is fundamental to development and requires proper energy engagement. One of the key energy sensing factors is AMP-activated protein kinase (AMPK), which regulates glucose uptake to ensure ATP production and nutrition supply during development. Here, we identify that the mutation of xgr, a gene encoding an ATPase, results in a reduced body size in Drosophila. Xgr is primarily expressed in the epithelial cells of the Malpighian tubules and the midguts. Loss of xgr leads to the inactivation of the AMPK signaling due to an increased ATP level. Glucose reabsorption in the Malpighian tubules is significantly reduced, as the Glut1 translocation to the plasma membrane is significantly disrupted in the absence of Xgr function. Our results suggest that Xgr function in the Malpighian tubules is essential to systemic glucose supply and energy homeostasis at the organismal level, thereby impacting body size. Our findings provide a mechanistic connection between energy homeostasis and animal size control during development.

Brassinosteroids (BRs) are essential phytohormones that broadly regulate plant growth, development, and adaptation to biotic and abiotic stresses. In Arabidopsis, apoplastic BR molecules are perceived by a plasma membrane-localized receptor complex comprising the ligand-binding receptor BRI1 and the co-receptor BAK1. While negative regulators of the BR receptor complex, such as BKI1, BIR3, and PUB12/13, have been well characterized, how BRI1 and BAK1 are positively modulated in the BR pathway remains largely unknown. In this study, a genetic screen involving overexpression of RLP genes in the bak1-3 bkk1-1 double mutant reveals that enhanced RLP51 expression partially suppresses the BR-deficient phenotypes of bak1-3 bkk1-1. RLP51 overexpression also partially rescues the weak bri1 mutant allele, bri1-301. Although the rlp51 single mutant exhibits wild-type-like phenotypes, it enhances BR-defective phenotypes in bri1-301 and bak1 serk1 mutants. RLP51 is next found to interact with both BRI1 and BAK1 without affecting BRI1-BAK1 interaction. Critically, co-expression of RLP51 with BRI1 or BAK1 significantly increases BRI1 and BAK1 protein abundances. RLP51 appears to promote protein synthesis rather than stabilize BRI1 and BAK1 proteins. Thus, our study identifies RLP51 as a positive regulator of BR signaling that enhances the protein levels of BRI1 and BAK1.

Finger millet (Eleusine coracana Gaertn.), a nutritionally rich and drought-resilient C₄ cereal, possesses exceptional grain storage longevity (up to 50 years). Here, we report a high-quality genome assembly of the allotetraploid cultivar C142, revealing extensive structural rearrangements between its two subgenomes (subA and subB), which are associated with asymmetric gene expression and subgenome dominance favoring subA. SubB diverged from subA and E. indica approximately 6.8 million years ago. Subsequently, two whole-genome duplication events shaped the current genome architecture, contributing to gene redundancy and adaptive potential. Notably, expansion of stress-related gene families, such as aldo-keto reductases, suggests a role in oxidative stress response and drought adaptation. Using genome-wide association studies, we identify several candidate genes associated with key agronomic traits. Among them, EcMDHAR, encoding monodehydroascorbate reductase, plays a critical role in enhancing drought tolerance. Different EcMDHAR haplotypes exhibit distinct expression profiles, supporting their functional relevance in drought adaptation. This genomic resource not only advances our understanding of polyploid genome evolution in millets, but also provides a foundation for genome-assisted improvement of drought resistance and nutritional quality in finger millet.

Cilia are microtubule-based organelles projecting from the cell surface with important sensory and motility functions. Ciliary defects are associated with diverse diseases collectively known as ciliopathies. However, the molecular mechanisms that govern ciliogenesis remain not fully understood. Here, we demonstrate that ubiquitin-specific protease 21 (USP21) is indispensable for cilium formation through its deubiquitinating activity. Usp21 knockout mice exhibit ciliary defects in multiple organs, such as the kidney, liver, and trachea. Our data also reveal a constant localization of USP21 at the centrosome and basal body during ciliogenesis. Mechanistically, USP21 interacts with dihydropyrimidinase-like 2 (DPYSL2) at the centrosome and removes lysine 48-linked ubiquitination from DPYSL2. Loss of USP21 leads to the proteasomal degradation of DPYSL2 and causes a significant reduction in its centrosome abundance, ultimately resulting in ciliary defects. These findings thus identify a critical role for the USP21-DPYSL2 axis in ciliogenesis and have important implications for health and disease.

Handedness is a fundamental behavioral trait in humans, with the majority exhibiting right-hand dominance. While its origins remain elusive, it is considered an innate genetic trait. This study demonstrates pawedness in mice (n = 473), comparable to human handedness, as an acquired trait rapidly emerging after limited unilateral paw training. Notably, acquired right-pawedness demonstrates greater conservativeness compared to left-pawedness, as evidenced by stronger stability and greater resistance to reversal. This results in a population right-paw dominance under random training conditions. Moreover, acquired pawedness also exhibits sex differences, with the initial preference proving more malleable in females. These findings unveil the acquired features of pawedness in mice. By illuminating possible behavioral laterality commonalities across species, the study proposes a postnatal hypothesis for the origins of human handedness: it is not an innate genetic trait as traditionally believed, but rather an environmentally acquired stable behavior whose development is actively guided by genetic predispositions.

The frequency of aneuploid gamete formation increases with maternal age, yet the effects of genetic variants on meiotic chromosome segregation accuracy during aging remain poorly understood. Using the multicellular organism Caenorhabditis elegans, we investigate the impact of mutations in the conserved cohesin complex on age-associated meiotic errors. Point mutations in the head domain of the cohesin component SMC-1, which alter local hydrophobicity, cause meiotic defects that vary with age. A severe mutation causes incomplete synapsis and defective crossover formation, and a minor one causes age-related diakinesis bivalent abnormalities. Notably, while the mild mutation causes defects only in aged worms, worms with the severe mutation exhibit significantly alleviated phenotypes with age. Genetic and cytological analyses suggest that this alleviation results from a slowed meiotic progression during early prophase, which restores impaired cohesin loading. These findings reveal that cohesin variants, meiotic progression speed during early prophase, and the overall duration of meiosis collectively shape the accuracy of meiotic chromosome segregation.

Penetrance is a crucial indicator for accurately assessing disease risk and plays a vital role in disease research, gene therapy, and genetic counseling. However, with penetrance data dispersed across various sources, efficiently accessing and consolidating this information becomes a challenge. A comprehensive platform that integrates penetrance is urgently needed. Here, we present PenCards, a global, community-contributed public archive of variant penetrance, by first collecting penetrance data from all published literature and then using large international cohorts to specifically calculate the penetrance of autism-related variants. PenCards contains a total of 244,531 variants, including 239,244 single nucleotide variants, 4994 insertions and deletions, and 293 copy number variants, covering approximately 300 phenotypes. We also provide a submission portal for the dynamic updating of penetrance. Additionally, to help users efficiently access genetic information, we comprehensively integrate over 150 variant- and gene-level resources. In summary, PenCards is a powerful platform designed to advance genetic research and diagnostics. PenCards is publicly available at https://genemed.tech/pencards/.

Gibbons are small, arboreal apes that play a critical role in tropical biodiversity and ecosystem ecology. However, nearly all species of gibbons are threatened by habitat loss, illegal trade, hunting, and other human activities. Long-term poor understanding of their genetics and evolution undermines effective conservation efforts. In this study, we analyse comparative population genomic data of four Nomascus species. Our results reveal strong genetic differentiation and gene flow among Nomascus species. Additionally, we identify genomic features that are potentially related to natural selection linked to vocalization, fructose metabolism, motor balance, and body size, consistent with the unique phenotype and adaptability of gibbons. Inbreeding, coupled with population declines due to climate change and historical human activities, leads to reduced genetic diversity and the accumulation of deleterious variations that likely affect cardiovascular disease and the reproductive potential of gibbons and further reduce their fitness, highlighting the urgent need for effective conservation strategies.

Improving nitrogen use efficiency (NUE) in rice is crucial for sustainable agriculture, yet remains a significant challenge due to its complex polygenic and environmental regulation. Although multiple NUE-associated genes have been identified, their intricate regulatory networks are poorly understood, especially under abiotic stresses such as drought, salinity, and extreme temperatures. This review systematically summarizes the genetic basis of NUE in rice, covering key genes involved in nitrogen uptake, translocation, assimilation, and remobilization. It further explores the crosstalk between nitrogen utilization and abiotic stress tolerance, highlighting integrative signaling nodes such as the dual nitrate/ABA receptor OsNRT1.1B. Finally, a comprehensive strategy is proposed to develop elite rice varieties with high NUE and multi-stress resilience, supporting the advancement of resource-efficient and climate-smart agriculture.