Journal of Genetics and Genomics

The application and prospects of spatial omics technologies in clinical medical research and molecular diagnostics

Xiaofeng Wu, Weize Xu, Da Lin, Leqiang Sun, Lit-Hsin Loo, Jinxia Dai, Gang Cao

2026, 53(2): 181-196. doi: 10.1016/j.jgg.2025.09.003

Abstract (0)

Abstract:
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.

The right is more conservative than the left: a postnatal hypothesis of handedness based on mice

Qingqing Wang, Jiesi Wang, Yan Wang, Xin Jin, Zhongsheng Sun

2026, 53(2): 197-208. doi: 10.1016/j.jgg.2025.11.005

Abstract (29) PDF (1)

Abstract:
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.

Receptor-like protein 51 regulates brassinosteroid signaling by promoting the abundances of BRI1 and BAK1

Yuan Fang, Pengcheng Li, Bingqing Tao, Yujun Wu, Beibei Liu, Chengbin Xiao, Jia Li, Kai He

2026, 53(2): 209-222. doi: 10.1016/j.jgg.2025.07.005

Abstract (0)

Abstract:
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.

Functional characterization of OsLT9 in regulating rice leaf thickness

Jian Wang, Dagang Chen, Haifei Hu, Yamei Ma, Tifeng Yang, Jie Guo, Ke Chen, Chanjuan Ye, Juan Liu, Xinqiao Zhou, Chuanguang Liu, Junliang Zhao

2026, 53(2): 223-233. doi: 10.1016/j.jgg.2025.07.010

Abstract (17)

Abstract:
Leaf thickness in rice critically influences photosynthetic efficiency and yield, yet its genetic basis remains poorly understood, with few functional genes previously characterized. In this study, we employ a pangenome-wide association study (Pan-GWAS) on 302 diverse rice accessions from southern China, identifying 49 quantitative trait loci (QTLs) associated with leaf thickness. The most significant locus, qLT9, is fine-mapped to a 79-kb region on chromosome 9. Transcriptomic and genomic sequence analyses identify LOC_Os09g33480, which encodes a protein belonging to Multiple Organellar RNA Editing Factor family, as the key candidate gene. Overexpression and complementation transgenic experiments confirm LOC_Os09g33480 (OsLT9) as the functional gene underlying qLT9, demonstrating a 24-bp Indel in its promoter correlates with the expression levels and leaf thickness. Notably, OsLT9 overexpression lines show not only thicker leaf, but also significantly enhanced photosynthetic efficiency and grain yield, establishing a link between leaf thickness modulation and yield enhancement. Population genomic analyses indicate strong selection for OsLT9 during domestication and breeding, with modern cultivars favoring thick leaf haplotype of OsLT9. This study establishes OsLT9 as a key regulator controlling leaf thickness in rice, and provides a valuable genetic resource for molecular breeding of high-yielding rice through optimization of plant architecture.

The auxin response factor OsARF12 modulates rice leaf angle via affecting shoot gravitropism

Fengjun Xian, Shuya Liu, Bin Xie, Jishuai Huang, Qiannan Zhang, Yimeng Xu, Xinrong Zhang, Chen Lv, Lin Zhu, Jun Hu

2026, 53(2): 234-245. doi: 10.1016/j.jgg.2025.06.005

Abstract (0)

Abstract:
Leaf angle is a pivotal agronomic trait that significantly influences crop architecture and yield. Plant hormones, such as auxin, play a critical role in regulating leaf angle; however, the underlying molecular mechanisms remain to be fully elucidated. Here, we reveal that the auxin response factor gene, OsARF12, which is highly expressed in the leaf lamina joint, negatively regulates rice (Oryza sativa L.) leaf angle via affecting shoot gravitropism. Overexpression lines of OsARF12 exhibit more erect leaf angles, while the osarf12 mutants display enlarged leaf angles compared to the wild type. Further studies demonstrate that OsARF12 directly activates the expression of Loose Plant Architecture1 (LPA1) and LAZY1 by binding to their promoters. The osarf12 mutant presents impaired shoot gravitropism, a phenotype consistent with that of the lpa1 and lazy1 mutants. Collectively, we elucidate the biological functions of OsARF12, which modulates leaf angle through its impact on shoot gravitropism by regulating the expression levels of LPA1 and LAZY1. This study provides insight into the role of auxin in determining rice leaf angle, potentially holding profound effects for the optimization of crop architecture.

Genetic landscape of hereditary cardiomyopathies and arrhythmias in China

Yang Lu, Zeyuan Wang, Shuyuan Zhang, Yaping Liu, Ye Jin, Zhuang Tian, Shuyang Zhang

2026, 53(2): 246-255. doi: 10.1016/j.jgg.2025.07.003

Abstract (13)

Abstract:
Hereditary cardiomyopathies and arrhythmias are major contributors to cardiovascular morbidity and mortality. The advent of next-generation sequencing (NGS) has made genetic testing more accessible, which is crucial for precise diagnosis and targeted therapeutic strategies. The aim of this study is to explore the landscape of genetic variants, the relationship between specific variants and clinical phenotypes, and the impact on clinical decision-making in China. A total of 1536 probands (median age, 37 years; 1025 males [66.7%]) with suspected hereditary cardiomyopathy or arrhythmia (covering 15 clinical phenotypes) are recruited from 146 hospitals across 30 provinces and cities in China. Positive results are confirmed in 390 of 1536 probands, leading to a diagnostic yield of 25.4%. Forty-two and three-tenths percent (n = 169) of family members carry the same variants as positive probands. Hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) are the predominant phenotypes, with MYBPC3 variants having the highest frequency in HCM and TTN variants in DCM. In 76.9% of the positive probands, the identified variants are helpful in clinical management, family screening, and fertility. This large-scale study provides significant insights into the genetic landscape of hereditary cardiomyopathies and arrhythmias in China.

USP21 deubiquitinates DPYSL2 and enhances its centrosomal abundance to promote cilium formation

Ting Song, Peng Zhou, Fengguo Zhang, Chunli Liu, Xueqing Han, Yiyang Yue, Mingzheng Hu, Shaodong Yan, Qingchao Li, Min Liu, Jun Zhou, Huijie Zhao

2026, 53(2): 256-268. doi: 10.1016/j.jgg.2025.06.006

Abstract (11) PDF (3)

Abstract:
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.

Whole-genome sequencing provides insights into the evolutionary adaptation and conservation of gibbons

Guiqiang Wang, Yajiang Wu, Song Wang, Ting Jia, Peng Yang, Zhongshi Xu, Wenhui Niu, Fen Shan, Chen Wang, Wu Chen, Ting Sun

2026, 53(2): 269-282. doi: 10.1016/j.jgg.2025.07.004

Abstract (23) PDF (2)

Abstract:
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.

Xgr is involved in body size control in Drosophila through promoting glucose uptake in the Malpighian tubules

Zhiwei Lin, Zihao He, Jianfeng Guo, Xiaofang Ji, Ze Hu, Yingsen Tang, Chuanxian Wei, Jiyong Liu, Wenqi Wu, Jun Ma, Renjie Jiao

2026, 53(2): 283-292. doi: 10.1016/j.jgg.2025.05.007

Abstract (0) PDF (0)

Abstract:
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.

Cohesin variants and meiotic timing shape chromosome segregation accuracy

Yuanyuan Liu, Bohan Liu, Shuo Wang, Li Zhao, Qian Li, Feifei Qi, Ruoxi Wang, Jun Zhou, Jinmin Gao

2026, 53(2): 293-304. doi: 10.1016/j.jgg.2025.06.003

Abstract (0)

Abstract:
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.

A telomere-to-telomere genome assembly of radish (Raphanus sativus L.) provides insights into QTL mapping of bolting traits

Feng Yang, Sihan Peng, Shuai Yuan, Maolin Ran, Xiaomei Li, Yuejian Li, Bin Liu, Ming Li, Chuibao Kong, Xiao Yang, Guohui Pan, Xiaoping Yong, Ke Ran, Na Kuang, Dawei Zhang, Honghui Lin

2026, 53(2): 305-320. doi: 10.1016/j.jgg.2025.07.014

Abstract (0)

Abstract:
Radish (Raphanus sativus L.) is an important cruciferous root vegetable, with bolting regulated by multiple genes. However, the genetic mechanisms underlying bolting regulation remain unclear. Here, the genome of the cultivar C60213 is assembled into a high-quality, gap-free telomere-to-telomere structure, spanning nine chromosomes and totaling 472.71 Mb, using a combination of Oxford Nanopore, PacBio, and Hi-C sequencing technologies. It identifies 49,768 protein-coding genes, 97.38% of which are functionally annotated. Repetitive sequences constitute 59.72% of the genome, primarily comprising long terminal repeats. A high-density genetic linkage map is constructed using an F₂ population derived from a cross between early- and late-bolting radishes, identifying seven major quantitative trait loci associated with bolting and flowering. RNA-seq and quantitative real-time PCR analysis reveal that the RsMIPS3 gene is found to be associated with bolting, with its expression decreasing during this process. Notably, RsMIPS3 overexpression in Arabidopsis delays bolting, confirming its role in regulating bolting time. These findings advance radish genome research and provide a valuable target for breeding late-bolting varieties.

Chromosome-level genome assembly of finger millet (Eleusine coracana) provides insights into drought resistance

Jiguang Li, Chaonan Guan, Xiaobo Li, Yanlan Wang, Jiayue He, Liqin Hu, Yaliang Shi, Yuqi He, Kaixuan Zhang, Rui Tang, Meiliang Zhou

2026, 53(2): 321-331. doi: 10.1016/j.jgg.2025.07.012

Abstract (0)

Abstract:
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.

PenCards: a global and community-contributed public archive of variant penetrance

Zhaopo Zhu, Ling Shang, Chuhan Shao, Zheng Wang, Xinxin Mao, Yuanfeng Huang, Pei Yu, Bin Li, Jinchen Li, Guihu Zhao

2026, 53(2): 332-342. doi: 10.1016/j.jgg.2025.07.001

Abstract (16)

Abstract:
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/.

3vGCIM: a compressed variance component mixed model for detecting QTL-by-environment interactions in RIL population

Mei Li, Yuan-Ming Zhang

2026, 53(2): 343-356. doi: 10.1016/j.jgg.2025.05.011

Abstract (21)

Abstract:
Existing quantitative trait locus (QTL) mapping had low efficiency in identifying small-effect and closely linked QTL-by-environment interactions (QEIs) in recombinant inbred lines (RILs), especially in the era of global climate change. To address this challenge, here we integrate the compressed variance component mixed model with our GCIM to propose 3vGCIM for identifying QEIs in RILs, and extend 3vGCIM-random to 3vGCIM-fixed. 3vGCIM integrates genome-wide scanning with machine learning, significantly improving power. In the mixed full model, we consider all possible effects and control for all possible polygenic backgrounds. In simulation studies, 3vGCIM exhibits higher power (∼92.00%), higher accuracy of the estimates for QTL position (∼1.900 cM²) and effect (∼0.050), and lower false positive rate (∼0.48‰) and false negative rate (<8.10%) in three environments of 300 RILs each than ICIM (47.57%; 3.607 cM², 0.583; 2.81‰; 52.43%) and MCIM (60.30%; 5.279 cM², 0.274; 2.17‰; 39.70%). In the real data analysis of rice yield-related traits in 240 RILs, 3vGCIM mines more known genes (57–60) and known gene-by-environment interactions (GEIs) (14–19) and candidate GEIs (21–23) than ICIM (27, 2, and 7), and MCIM (21, 1, and 3), especially in small-effect and linked QTLs and QEIs. This makes 3vGCIM a powerful and sensitive tool for QTL mapping and molecular QTL mapping.

Universal single-copy ortholog benchmark gene set for bryophytes

Xuping Zhou, Tao Peng, Jin Yu, Shanshan Dong, Yang Liu

2026, 53(2): 357-359. doi: 10.1016/j.jgg.2025.07.009

Abstract (0)

Abstract:

2026 Vol. 53, No. 2