Journal of Genetics and Genomics

Lipid metabolism and metabolites: emerging roles in systemic physiology and metabolic diseases

Jiesi Xu, Dongliang Lu, Xun Huang

2026, 53(7): 1143-1158. doi: 10.1016/j.jgg.2026.01.006

Abstract (119)

Abstract:
Lipids function as central regulators of cellular and systemic physiology through their roles in energy storage, membrane architecture, signaling, and nutrient transport. Maintaining lipid metabolic balance is essential, as its disruption underlies a broad spectrum of metabolic and metabolic-related disorders, including fatty liver disease, obesity, cardiovascular disease, neurodegeneration, and infections. Recent studies have uncovered roles for phospholipids, sphingolipids, lipid-related metabolites, and lipoproteins as metabolic modulators in regulating disease development or mediating inter-organ communication. In this review, we summarize emerging insights into lipid metabolism and metabolite function, with an emphasis on their contribution to the pathogenesis of diseases. We further highlight how these discoveries reshape our understanding of lipid biology and open new avenues for therapeutic intervention.

Gene-targeted versus broad-spectrum therapies in ALS: comparative lessons and strategic outlook

Yihan Shen, Siyu Shen, Zhen-Ge Luo

2026, 53(7): 1159-1179. doi: 10.1016/j.jgg.2026.01.012

Abstract (45)

Abstract:
Amyotrophic lateral sclerosis (ALS) is a relentless and fatal neurodegenerative disorder characterized by the progressive loss of motor neurons, leading to muscle weakness, paralysis, and ultimately, respiratory failure. Despite a growing understanding of its complex pathophysiology, therapeutic options remain limited. This review critically analyzes recent clinical advances by comparing two divergent strategies, including precision gene-targeted therapies for monogenic ALS subtypes and broad-spectrum agents for the wider sporadic population. While gene therapies like tofersen demonstrate clear molecular target engagement, their translation to robust clinical benefit remains a challenge. In contrast, broad-spectrum agents have faced consistent late-stage failures, often due to the disease's underlying diversity, which undermines a one-size-fits-all approach. We argue that this heterogeneity, coupled with a lack of predictive biomarkers and the difficulty of late-stage intervention, represents the core barrier to progress. The future of ALS therapeutics therefore depends on a strategic pivot toward personalized medicine. This requires prospectively stratifying patients, developing rational combination therapies, and intervening earlier in the disease course, ultimately treating ALS as a syndrome of distinct molecular diseases rather than a single entity.

Transcriptional, epigenetic, and post-translational regulation of plant autophagy

Yao Wang, Chao-Ying Liu, Liang Chen, Si-Hai Guo, Shi Xiao, Hua Qi

2026, 53(7): 1180-1193. doi: 10.1016/j.jgg.2026.01.007

Abstract (153)

Abstract:
Autophagy is a highly conserved intracellular recycling process in eukaryotes that delivers cellular components to the lysosome or vacuole for degradation, thereby maintaining intracellular homeostasis. Acting as a quality control system, autophagy plays a pivotal role in plant growth, development, and adaptation to environmental challenges. The regulation of autophagy under stress conditions involves multi-layered mechanisms, including transcriptional, epigenetic, and post-translational controls. Transcription factors from families such as WRKY, NO APICAL MERISTEM/ARABIDOPSIS TRANSCRIPTION ACTIVATION FACTOR/CUP-SHAPED COTYLEDON (NAC), and basic leucine zipper (bZIP) directly bind to the promoters of autophagy-related (ATG) genes, thereby integrating stress-responsive signal pathways to orchestrate autophagic activity dynamically. Epigenetic modifications, including histone modifications, DNA methylation, N⁶-methyladenosine (m⁶A) methylation, and microRNA-mediated silencing, further fine-tune expression of ATG genes in response to changing environments. At the post-translational level, modifications such as phosphorylation, ubiquitination, acetylation, persulfidation, and S-nitrosylation serve as rapid regulatory switches that modulate autophagosome formation under stress. This review summarizes recent advances in elucidating these regulatory layers, highlighting how these regulators collectively modulate autophagy to improve plant tolerance to environmental cues. Unraveling these mechanisms will expand our understanding of the autophagy regulatory network in plants and provide potential strategies for improving stress tolerance in crops.

Integration of light, carbon, and nitrogen pathways in regulating rice yield

Xiaokang Wu, Kun Wu, Jigang Li, Rongcheng Lin

2026, 53(7): 1194-1209. doi: 10.1016/j.jgg.2026.01.009

Abstract (121)

Abstract:
Rice productivity arises from an interdependent system: optimal nitrogen utilization enables efficient light signaling, photosynthetic energy capture, and carbon fixation (ultimately yielding carbohydrates), while these processes are fine-tuned by the nitrogen status they regulate, collectively optimizing growth and yield. Light signaling, mediated by photoreceptors, converts environmental cues into transcriptional reprogramming that elicits specific cellular responses. Concurrently, photosynthesis converts light into chemical energy and sugar signals that orchestrate plant growth and development. Nitrogen serves not only as a fundamental building block for all core biomolecules but also as a master regulatory signal, ultimately determining crop yield by governing both the physical structure and developmental programs of plants. The synergistic coordination of light, carbon, and nitrogen metabolism thus underlies crop productivity by regulating carbon-nitrogen balance and associated physiological processes. This review summarizes the dual role of light as both a signal and an energy source, and its integration with sugar and nitrogen metabolism across multiple biological levels to shape yield traits in rice. We further analyze how key transcription factor networks function as central hubs, integrating light, carbon, and nitrogen pathways to enhance photosynthetic capacity, nitrogen assimilation, and reproductive development, providing strategic insights for breeding high-yielding rice varieties with superior resource-use efficiency.

Ancient genomic profile of the Shatuo Turkic leader Li Keyong

Yao Yu, Xiaoguang Zhu, Xin Chang, Zixiao Huang, Panxin Du, Xiaoying Ren, Baoshuai Zhang, Ke Wang, Yishan Wu, Sheng Han, Li Jin, Yi Zheng, Hailiang Meng, Shaoqing Wen

2026, 53(7): 1210-1222. doi: 10.1016/j.jgg.2026.04.015

Abstract (406)

Abstract:
The Shatuo Turks played a pivotal role in late Tang and Five Dynasties China. However, similar to other Turkic groups, the genetic history and population origins of the Shatuo remain poorly understood. This study presents a genomic investigation of a Shatuo leader through the analysis of ancient DNA from Li Keyong (856 CE-908 CE), founder of the Later Tang dynasty, providing an opportunity to elucidate the genetic composition and origins of this pivotal group. Through comprehensive population genetic analyses, including PCA, ADMIXTURE analysis, f-statistics, and qpAdm modeling, we found that Li Keyong had a nearly balanced admixture, with 53.4% Ancient Northeast Asian and 46.6% Western Steppe ancestry. Additionally, he carried a Western Eurasian paternal lineage (R1a1a1b2∼AM01870) and an Eastern Steppe maternal lineage (C4a1a+195). This genetic profile contrasts sharply with the predominantly Northeast Asian ancestry observed in the Ashina royal clan, highlighting significant genetic heterogeneity within Turkic confederations. Our results suggest that the Shatuo emerged from complex cross-Eurasian interactions, consistent with the hypothesis of a multi-ethnic origin.

Brassinosteroids negatively regulate plant de novo root regeneration

Yuan-Yuan Dong, Yu-Tong Jiang, Yuan-Xin Wang, Jin-Hui Chang, Jing-Ting Yang, Li-Qin Hu, Lu-Han Yang, Min Xu, Yuan-Yuan Zhang, Wu Liu, Wen-Hui Lin

2026, 53(7): 1223-1234. doi: 10.1016/j.jgg.2026.04.018

Abstract (157)

Abstract:
De novo root regeneration (DNRR) is essential for plant survival under mechanical damage and agricultural productivity, and plant hormones play a pivotal role in this process. While auxin, jasmonate (JA), and ethylene are known to be involved in DNRR, the role of brassinosteroids (BR) remains unreported. This study reveals that the reduced BR signaling promotes DNRR, whereas elevated BR signaling suppresses DNRR. Then we further validate that this mechanism is conserved across diverse plant species, including Brassica napus, Nicotiana benthamiana, and Solanum lycopersicum. Studies on the regulatory mechanism indicate that BR regulates DNRR by modulating auxin-related pathways. BR induces the transcription factor BZR1, which directly represses auxin transporter genes (PIN1 and PIN3), thereby reducing auxin levels at the wound sites of leaf explants and inhibiting root primordia formation. Besides, BZR1 also transcriptionally suppresses root meristem initiation-related genes (WOX5 and LBD16) to inhibit DNRR. This study demonstrates BR function in plant DNRR, refines the network of hormonal regulation of DNRR, and provides an important clue for improving plant rooting efficiency in agriculture.

The HPCA1-VDAC3 module mediates the humidity adaptation trade-off by interfering with ROS homeostasis in Arabidopsis thaliana

Songyi Yang, Luna Tan, Zhen Yan, Meng Liu, Yongqi Hu, Yuhan Zou, Feifei Huang, Xuerui Li, Jin Yan, Wensen Fu, Ruyun Liang, Si Tang, Mengyun Guo, Qiusai Wu, Songfeng He, Wenli Chang, Wei Liu, Yu Han, Yan Song, Xuemeng Gao, Yingjun Yao, Kai Yang, Weitao Jia, Feihua Wu, Jianquan Liu, Huanhuan Liu

2026, 53(7): 1235-1247. doi: 10.1016/j.jgg.2026.02.013

Abstract (13)

Abstract:
Distinct Arabidopsis thaliana ecotypes differ in humidity adaptation, with Tibet ecotype adapted to arid habitats exhibiting lower submergence tolerance than humidity-adapted counterparts. Here, we identify a unique 332-bp transposable element (TE) insertion in the promoter of HYDROGEN-PEROXIDE-INDUCED Ca²⁺ INCREASES 1 (HPCA1) specific to the Tibet ecotype. This insertion upregulates HPCA1 expression by the recruitment of active histone modifications. HPCA1, in turn, negatively regulates submergence tolerance through its interaction with VOLTAGE-DEPENDENT ANION CHANNEL 3 (VDAC3), a voltage-dependent ionic channel localized in the mitochondrial outer membrane. Transcriptomic analyses indicate that the HPCA1-VDAC3 module modulates submergence tolerance, at least in part, by regulating RBOHD, WRKY46, and MYC2 to maintain reactive oxygen species (ROS) homeostasis. Additionally, HPCA1 facilitates VDAC3 phosphorylation and inhibits antioxidant enzyme activities, potentially disrupting ROS balance. A negative correlation between HPCA1 expression levels and precipitation is observed across global A. thaliana ecotypes. Together, our results suggest that the HPCA1-VDAC3 module integrates H₂O₂ signaling and ROS homeostasis via regulation of RBOHD, WRKY46, and MYC2, thereby mediating a trade-off in humidity adaptation in A. thaliana and providing insights for breeding flooding-tolerant crops.

The ultra-conserved lncRNA Crnde regulates neural differentiation by targeting Gbx2 during embryonic development of the thalamus

Wen-Zhu Hu, Ya-Yun Gu, Yuan-Lin He, Yuan Hong, Yue-Wen He, Zi-Cheng Zhang, Yuan-Hao Wang, Jia-Ning Sun, Xiao Han, Yan Liu, Zhi-Bin Hu

2026, 53(7): 1248-1265. doi: 10.1016/j.jgg.2026.02.002

Abstract (99)

Abstract:
The thalamus regulates sensory processing, cognition, and sleep, yet the molecular mechanisms underlying its development remain incompletely understood. Long noncoding RNAs (lncRNAs), particularly evolutionarily conserved ones, are highly enriched in the brain. Using public mRNA databases, we screen for lncRNAs with embryonic brain expression and harboring ultraconserved noncoding elements (UCNEs) in humans and mice, identifying colorectal neoplasia differentially expressed (Crnde). It exhibits stage-specific upregulation in the embryonic thalamus. The Database of Genomic Variation and Phenotype in Humans using Ensembl Resources (DECIPHER) suggests a potential association between Crnde and intellectual disability. Crnde-deficient mice display anxiety-like behaviors and spatial memory deficits. Furthermore, Crnde ablation increases progenitor cell numbers and impairs neuronal differentiation during embryonic thalamic development. Mechanistically, Crnde modulates the mRNA expression of gastrulation brain homeobox 2 (Gbx2), a gene critical for thalamic development. Collectively, our results implicate lncRNA Crnde in the proper progression of embryonic thalamic development in mice.

Optic neuropathy arising from the synergy between YARS2 and mitochondrial COX1 mutations

Huiying Li, Cheng Ai, Xiaofen Jin, Jing Wang, Jun Yu, Yinglong Gao, Douglas C. Wallace, Min-Xin Guan

2026, 53(7): 1266-1282. doi: 10.1016/j.jgg.2026.02.003

Abstract (130)

Abstract:
Leber hereditary optic neuropathy (LHON) is a paradigm for mitochondrial retinopathy. Here, we investigate the mechanism underlying the interaction between nuclear modifier and mtDNA mutation(s) that manifests optic neuropathy in vivo to develop an effective therapeutic approach for this disease, using mouse models bearing LHON-linked Yars2^G186V or COI^V421A mutation alone and double mutations. Yars2^G186V alters mitochondrial translation and assembly and activities of complex I, III, and IV, while COI^V421A reduces complex IV activity. However, a single Yars2^G186V or COI^V421A mutation causes mild declines in ATP production and yields relatively mild degeneration of retinal ganglion cells (RGCs). Notably, the synergy between COI^V421A and Yars2^G186V mutations aggravates mitochondrial dysfunction and oxidative stress. Interestingly, COI^V421A mainly promotes apoptosis, and Yars2^G186V contributes to ferroptosis. The combination of two mutations accelerates the degeneration of RGCs and photoreceptors. Strikingly, AAV-mediated Yars2 expression in the mouse retina carrying both Yars2^G186V and COI^V421A mutations corrects the defective translation and ferroptosis arising from the Yars2^G186V mutation and remarkably improves mitochondrial function and causes morphologic and functional recovery of RGCs and photoreceptors. These findings provide mechanistic insights into the pathophysiology of LHON arising from nuclear modifiers and mtDNA mutation(s) and potential therapeutic strategies for LHON and other mitochondrial diseases.

The Taizhou Longitudinal Study: a population-based biobank resource of genetic and biochemical biomarkers for precision medicine in China

Yanfeng Jiang, Linyao Lu, Zhenqiu Liu, Ziyu Yuan, Huangbo Yuan, Kelin Xu, Tiejun Zhang, Xiang Zhang, Min Fan, Yuguo Chen, Weimin Ye, Jiucun Wang, Ming Lu, Li Jin, Chen Suo, Xingdong Chen

2026, 53(7): 1283-1291. doi: 10.1016/j.jgg.2026.02.004

Abstract (179)

Abstract:
The Taizhou Longitudinal Study (TZL) is a population-based prospective cohort initiated in 2007, recruiting over 201,000 adults aged 20-80 from urban and rural areas of Taizhou, Jiangsu Province, China. The cohort is extensively phenotyped through baseline questionnaire-based interviews, physical examinations, biochemical assays, and longitudinal follow-up using health records and repeated assessments. A wide range of biospecimens, including blood, urine, saliva, and feces, have been collected to enable omics-level profiling. Genome-wide genotyping has been performed for approximately 50,000 participants recruited from 2009 to 2014. Here, we present an integrated overview of the existing and planned genetic and phenotypic resources, describe genotyping and quality control procedures, and assess cryptic relatedness and population structure, followed by genome-wide association analyses of 66 physical and biochemical traits. In total, 533 independent loci reach Bonferroni significance after clumping. These analyses identify 55 previously unreported loci, demonstrating the capacity of the TZL to elucidate the genetic architecture of complex traits in East Asian populations. By integrating high-quality phenotypic and genotypic data, the TZL enables a comprehensive investigation of gene-environment interactions in the Chinese population. With ongoing expansions and development of a controlled-access data-sharing platform, the TZL is positioned as a valuable resource for precision medicine and public health research.

Bridging clinical narratives and structured phenotypes with large language models and sentence transformers

Jihao Cai, Guozhuang Li, Yongxin Yang, Kexin Xu, Sen Zhao, Timothy Hospedales, Lina Zhao, Jianle Yang, Zhihong Wu, Terry Jianguo Zhang, Zefu Chen, Nan Wu

2026, 53(7): 1292-1304. doi: 10.1016/j.jgg.2026.02.009

Abstract (135)

Abstract:
Structured phenotypes are important for Mendelian disorder diagnosis, gene-phenotype association studies, and standardized phenotypic data sharing. Although electronic health records (EHRs) contain abundant phenotypic information, much of it is unstructured. Early automated phenotyping methods are rule-based, limiting their ability to capture semantic variability and contextual information. Recent deep learning approaches, including BERT-based models and large language models (LLMs), improve semantic understanding but still face key limitations. BERT-based methods are constrained by limited context windows, requiring text chunking and aggregation for long clinical narratives, while LLMs that directly generate Human Phenotype Ontology (HPO) identifiers may produce non-existent identifiers. To address these challenges, we propose LLM-Enhanced Automated Phenotyping (LEAP), a two-stage framework that integrates an LLM for free-text phenotype extraction with a sentence-transformer model fine-tuned on a large-scale dataset of 5,330,557 instances for HPO mapping. This design handles long inputs while ensuring valid and deterministic HPO identifier outputs. On a real-world EHR test set, LEAP achieves relative improvements of 19.68%-412.68% in precision and 44.14%-298.77% in F1 score compared with existing tools, while maintaining robust performance on external benchmarks. LEAP can be integrated with gene prioritization tools to provide standardized phenotype inputs for downstream analyses. LEAP is available at phenogemini.org/extract.

Fibroblast-directed melanocyte recruitment via Cxcl12-Cxcr4 axis promotes post-inflammatory hyperpigmentation and skin barrier protection in zebrafish

Shizheng Zhao, Si Li, Chenyuliang Zhang, Zheng Tang, Ao Zhang, Cong Huang, Kefan Cheng, Tao Yu, Yan Yan, Zilong Wen

2026, 53(7): 1305-1318. doi: 10.1016/j.jgg.2026.02.017

Abstract (0)

Abstract:
Post-inflammatory hyperpigmentation (PIH) is a common skin disorder characterized by brown or black macules. It can be categorized as transient, typically resolving within 6-12 months, or permanent, persisting for years. While the pathogenesis of PIH is commonly linked to localized melanocyte overactivation, the precise cellular and molecular basis for this dysregulation, as well as its physiological significance, remains poorly defined. Using an acetic acid-induced zebrafish model, we identify melanocyte migration as a critical driver of hyperpigmentation. This process is independent of immune cells but driven by fibroblasts, which secrete Cxcl12a to recruit melanocytes via the Cxcl12a-Cxcr4a axis. Fibroblast ablation irreversibly disrupts melanocyte patterning, indicating that aberrant fibroblast activity dictates the permanence of PIH. The recruited melanocytes form a dual protective barrier against both UV-induced DNA damage and microbial intrusion. The translational relevance of this mechanism is underscored by upregulated CXCL12 expression in fibroblasts from human PIH-related conditions such as keloids, acne, and atopic dermatitis. Therapeutically, the FDA-approved CXCR4 antagonist AMD3100 (Plerixafor) effectively prevents and attenuates PIH in our model. Our findings elucidate a fibroblast-mediated mechanism of melanocyte recruitment in PIH, uncover previously unappreciated barrier functions of melanocytes in skin repair, and propose a promising repurposed treatment strategy.

The ARHGAP10-202aa protein encoded by circARHGAP10 promotes skeletal muscle development and regeneration

Liyin Zhang, Yaoyao Ma, Dandan Zhong, Liangchen Gao, Ke Huang, Xinxin Li, Zhipeng Li, Jieping Huang, Hui Li, Ningbo Chen, Jian Wang

2026, 53(7): 1319-1331. doi: 10.1016/j.jgg.2026.01.008

Abstract (104)

Abstract:
Muscle growth and development are fundamental biological processes with significant implications for both human health and livestock production. Although circular RNAs (circRNAs) have long been regarded as noncoding RNAs, recent studies suggest that some circRNAs possess protein-coding potential. However, the biological roles and mechanisms of circRNA-encoded proteins remain poorly understood. Here, we identify circARHGAP10 as a protein-coding circRNA in cattle skeletal muscle that encodes a 202-amino acid protein, ARHGAP10-202aa, through an internal ribosome entry site (IRES)-dependent mechanism. ARHGAP10-202aa expression is confirmed by in vitro translation, immunodetection with a specific antibody, and Western blotting analysis. Functional assays reveal that ARHGAP10-202aa interacts with myosin light chain 6 (MYL6) to promote myoblast differentiation. Moreover, in vivo overexpression of ARHGAP10-202aa significantly enhances MYL6 expression and accelerates the regeneration of injured tibialis anterior muscle in mice. These findings not only expand our understanding of the role of circRNAs in muscle biology but also underscore the functional significance of circRNA-encoded proteins in muscle recovery and regeneration.

GenomeSyn-II: a comparative genomics framework integrating synteny visualization

Zu-Wen Zhou, Hong-Yun Zhao, Yi-Bo Chai, Ru-Peng Zhao, Yong-Qing Qian, Yuan-Yuan Zhong, Yan-Han Shao, Ling-Ling Chen, Jia-Ming Song

2026, 53(7): 1332-1335. doi: 10.1016/j.jgg.2026.01.011

Abstract (188)

Abstract:

Polyploidy-induced epigenetic priming underlies enhanced salinity tolerance in soybean

Lei Wang, Yun Li, Ying Liu, Xinyu Jiang, Wu Jiao, Longfei Wang, Qingxin Song

2026, 53(7): 1336-1339. doi: 10.1016/j.jgg.2026.01.001

Abstract (246)

Abstract:

Centromere architecture and sex chromosome evolution in garden asparagus revealed by a gap-free haplotype-resolved genome

Ke-Li Jia, Yi Wang, Xia Li, Rui-Yan Song, Chun-Xia Yang, Hao-Han Ning, Yan-Cun Bao, Yu-Lan Zhang, Lu-Xian Liu, Wu-Jun Gao, Shu-Fen Li

2026, 53(7): 1340-1343. doi: 10.1016/j.jgg.2026.02.001

Abstract (195)

Abstract:

2026 Vol. 53, No. 7