遗传最新文献

{"title":"On the role of Y chromosome loss in malignancies: the driving mechanisms and potentials in precision oncology.","authors":"Jia-Zhi Su, Li-Na Zhu, Xue Chen, Xu Wang, Xi-Han Guo","doi":"10.16288/j.yczz.25-329","DOIUrl":"https://doi.org/10.16288/j.yczz.25-329","url":null,"abstract":"<p><p>Biological sex is a critical determinant influencing the incidence, progression, clinical presentation, and prognosis of human diseases. Beyond sex-specific tumors, men typically exhibit higher morbidity and mortality rates in nearly all tumors compared to women. However, the genetic mechanisms underlying the cancer sex bias are not definitive. Loss of Y chromosome (LOY), the most prevalent somatic mutation in healthy males, frequently occurs in individuals over 50 years of age. On one hand, LOY in peripheral blood immune cells is strongly associated with increased tumor susceptibility. On the other hand, LOY also frequently occurs within tumor cells themselves, leading to the loss of Y-chromosome-linked tumor suppressor genes and non-coding RNAs, thereby reshaping the tumor microenvironment through mechanisms such as metabolic reprogramming and altering tumor immunity. Strikingly, LOY is a \"contagious\" mutation, which means malignant cells with LOY cause the same mutation in tumor-infiltrating immune cells, and the synergistic interaction between two types of LOY cells accelerates tumor evolution. Given the widespread occurrence of LOY in tumors and its crucial role in malignant progression, LOY holds great promise as a biomarker for early diagnosis, classification, and staging, as well as a potential target for precision therapy. Here, we summarize the mechanisms by which LOY drives malignant progression in solid tumors from the perspectives of tumor-cell-intrinsic LOY, LOY in tumor-infiltrating immune cells, and their crosstalk. We also discuss the developmental opportunities and translational potential of LOY in precision oncology. This review aims to provide novel insights into the molecular basis of sex disparities in tumors and to identify potential molecular targets for precision prevention, diagnosis, and treatment.</p>","PeriodicalId":35536,"journal":{"name":"遗传","volume":"48 8","pages":"781-795"},"PeriodicalIF":0.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148798906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Paleoproteomics reveal the genetic characteristics of Middle Pleistocene <i>Homo erectus</i> in East Asia.","authors":"Zi-Yi Zou, Hui-Yun Rao, Qiao-Mei Fu","doi":"10.16288/j.yczz.26-115","DOIUrl":"https://doi.org/10.16288/j.yczz.26-115","url":null,"abstract":"<p><p><i>Homo erectus</i> remains have been found in Africa, Eurasia, and Southeast Asia, with a fossil record dating back to 2 million years, holding a significant place in human evolution. However, due to limited molecular evidence, its genetic characteristics, diversity, and potential connections to other archaic homonins and modern humans have long remained unresolved. To address these issues, a research team led by Qiaomei Fu from the Institute of Vertebrate Paleontology and Paleoanthropology of the Chinese Academy of Sciences, in collaboration with other archaeological institutions, successfully extracted ancient enamel proteins from six Middle Pleistocene <i>H. erectus</i> teeth (~0.4 Ma) from the Zhoukoudian, Hexian, and Sunjiadong sites. Further in-depth paleoproteomic analyses revealed the following breakthroughs. First, a quantitative sex determination pipeline was established based on male-specific amelogenin, Y isoform (AMELY), confirming that five of these specimens are male and one is female. Second, two genetically specific amino acid variants in ameloblastin (AMBN) were identified in all specimens from three sites. One is a newly discovered variant, AMBN-253G, which has not been found in any other archaic or modern human populations. It represents a molecular marker specific to the East Asian Middle Pleistocene <i>H. erectus</i> lineage, providing solid evidence that <i>H. erectus</i> specimens from Zhoukoudian, Hexian, and Sunjiadong sites belonged to the same evolutionary lineage. The other variant, AMBN-273V, has previously been identified in Denisovans. However, genetic analysis in this study reveals that this variant may have been introduced into Denisovans through populations related to these Middle Pleistocene <i>H. erectus</i>, and some of which subsequently contributed to certain modern human populations from Southeast Asia or Oceania. This study obtains lineage-specific molecular information from <i>Homo erectus</i> fossils for the first time, and reshapes our understanding of hominin evolution and the history of genetic admixture in East Asia.</p>","PeriodicalId":35536,"journal":{"name":"遗传","volume":"48 8","pages":"753-758"},"PeriodicalIF":0.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148798873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular mechanisms of chronic dietary cholesterol-driven remodeling of LDLR protein fate.","authors":"Xue Feng","doi":"10.16288/j.yczz.26-155","DOIUrl":"10.16288/j.yczz.26-155","url":null,"abstract":"<p><p>The hepatic low-density lipoprotein receptor (LDLR) mediates the clearance of circulating low-density lipoprotein (LDL) and is a key determinant of cholesterol homeostasis. However, how nutritional cues such as chronic dietary cholesterol regulate LDLR intracellular trafficking and protein turnover through specific molecular switches remains poorly understood. Dr. Alan Saltiel's team at the University of California San Diego discovered a cholesterol stress-response pathway mediated by Ral GTPases, revealing a new mechanism by which dietary cholesterol reshapes LDLR protein fate and thereby affects cholesterol homeostasis. The study found that chronic dietary cholesterol loading or sustained Ral activation reduces LDLR protein levels. Mechanistically, chronic cholesterol loading activates Ral GTPases by increasing RAS activity. Activated Ral, on the one hand, recruits the RalBP1-REPS1 endocytic complex to promote LDLR internalization and lysosomal trafficking while inhibiting LDLR recycling back to the cell surface. On the other hand, Ral activation promotes the processing and lysosomal localization of cathepsin A (CTSA) and reduces its extracellular secretion, thereby enhancing CTSA-mediated LDLR degradation. This process occurs independently of LDLR transcriptional regulation or PCSK9-mediated LDLR degradation. Inhibition of CTSA stabilizes LDLR protein and promotes LDL uptake and plasma cholesterol clearance. Human genetic analyses further indicate that key components of this pathway are associated with plasma lipid levels and cardiovascular disease risk. This study reveals a dietary cholesterol-activated Ral-CTSA-LDLR protein homeostasis pathway, providing a new mechanistic framework for understanding how nutritional stress disrupts cholesterol metabolism and identifying a potential therapeutic target distinct from existing treatment strategies for hypercholesterolemia and cardiovascular disease.</p>","PeriodicalId":35536,"journal":{"name":"遗传","volume":"48 8","pages":"759-763"},"PeriodicalIF":0.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148798885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>PIK3CA</i> in-frame deletion-activated PI3K/AKT signaling pathway drives macrodactyly.","authors":"Jing-Heng Wu, Shan-Lin Chen, Yun-Hao Xue, Peng-Cheng Li, Meng-Meng Tian","doi":"10.16288/j.yczz.25-340","DOIUrl":"https://doi.org/10.16288/j.yczz.25-340","url":null,"abstract":"<p><p>Macrodactyly is a congenital abnormality characterized by overgrowth of single or multiple digits, frequently accompanied by pathological changes in bone, soft tissue, and nerve tissue, and is caused mostly by somatic variants. Previous studies have demonstrated that macrodactyly is predominantly caused by pathogenic variants in the <i>PIK3CA</i> gene, yet the underlying molecular mechanism remains unclear. In this study, we analyzed 13 patients clinically diagnosed with isolated macrodactyly. Through whole-exome and Sanger sequencing, we identified one pediatric patient carrying a novel mosaic <i>de novo</i> in-frame deletion mutation (c.307_312del/p.Glu103_Pro104del) in the <i>PIK3CA</i> gene, which was not detected in either parent. According to the American College of Medical Genetics and Genomics (ACMG) guidelines, we classified this mutation as a variant of uncertain significance (PM4+PM2_Supporting+PM6_Supporting). Protein structure prediction analysis indicated that this in-frame deletion altered the protein's local conformation and surface electrostatic potential. Furthermore, the wild-type and mutant expression vectors were constructed, including the well-established pathogenic mutation c.353G>A/p.Gly118Asp in <i>PIK3CA</i> gene as a control. We transfected these vectors into HEK293T cells for functional analyses, respectively. The results showed that although this mutation did not significantly affect <i>PIK3CA</i> mRNA or protein expression levels, it promoted the phosphorylation of downstream AKT protein at both Thr308 and Ser473. Therefore, the mutation may express the localized overgrowth phenotype by activating the PI3K/AKT signaling pathway. This study not only expands the genetic variant spectrum of macrodactyly, but also further clarifies the role of the PI3K/AKT pathway in the <i>PIK3CA</i>-related overgrowth.</p>","PeriodicalId":35536,"journal":{"name":"遗传","volume":"48 8","pages":"796-806"},"PeriodicalIF":0.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148798922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Operational model of the French livestock and poultry genetic resources management system and its implications.","authors":"Xiao-Jing Zhang, Ai-Ling Wang, Jing-Juan Zhao, Li-Min Chuan, Hui Zhang, Zhi-Hui Yan","doi":"10.16288/j.yczz.26-040","DOIUrl":"https://doi.org/10.16288/j.yczz.26-040","url":null,"abstract":"<p><p>As the largest agricultural producer in the European Union, France has established a mature and systematic livestock and poultry genetic resources management system. Based on comprehensive domestic legislation and effectively aligned with EU regulations, this system forms a governance structure characterized by clear responsibilities and multi-stakeholder collaboration. National regulatory authorities, public research institutions, industry organizations, and breeding service institutions work in a coordinated manner, with close linkages among the government, research community, and industry to ensure the conservation, dynamic monitoring, and sustainable utilization of genetic resources. For different livestock and poultry species such as ruminants, pigs, and poultry, France has developed differentiated genetic improvement pathways, supported by quality assurance and lifetime animal traceability mechanisms. This paper puts forward targeted suggestions for the conservation of livestock and poultry genetic resources in China, focusing on key areas such as forming a multi-stakeholder collaborative governance pattern, improving conservation mechanisms, promoting the layout of genetic improvement adapted to different livestock and poultry species, and ensuring quality traceability.</p>","PeriodicalId":35536,"journal":{"name":"遗传","volume":"48 7","pages":"659-670"},"PeriodicalIF":0.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148473138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating cases, enhancing interaction, and promoting learning through assessment: teaching reform and practical outcomes of medical genetics under the OBE concept.","authors":"Shi-Qian Liang, Fan Fan, Yi-Yang Hu, Jun-Long Zhao, Chun-Chen Gao, Liang Wang, Xiu-Li Cao, Lei Feng, Hong-Yan Qin","doi":"10.16288/j.yczz.25-302","DOIUrl":"https://doi.org/10.16288/j.yczz.25-302","url":null,"abstract":"<p><p>In the new era, the teaching of Medical Genetics requires medical students to not only master solid knowledge, but also possess practical abilities in diagnosing and treating clinical genetic diseases. This paper systematically elaborates on the design and practical exploration of teaching reform in the Medical Genetics course under the Outcome-Based Education (OBE) concept. By constructing a structured teaching system closely aligned with clinical practice, building a teaching model centered on clinical cases, carrying out diverse teaching activities, developing a \"boundless classroom\", and establishing a multi-dimensional assessment system, we have achieved a deep integration of knowledge transmission and clinical reasoning training. The teaching effectiveness has shown that this model significantly enhances students' case analysis abilities, learning motivation, and innovative capacity. However, the implementation process has also revealed deep-seated challenges in the practical teaching component, such as students facing difficulties in getting started, employing unsystematic methods, producing superficial results, and the imperfection of the evaluation mechanism. Drawing on exemplary domestic teaching cases, this paper proposes that future efforts must synergize two dimensions: \"resource support\" and \"pedagogical design\". This involves constructing a tiered, progressive practical ability training chain, improving the faculty development support system, and exploring the use of artificial intelligence to establish process-oriented data platforms and diversified evaluation mechanisms. By putting the OBE concept into practice, we aim to promote a deep transformation of the Medical Genetics course from \"knowledge transmission\" to \"competency development\", thereby laying a solid foundation for cultivating outstanding medical talent capable of meeting future medical demands.</p>","PeriodicalId":35536,"journal":{"name":"遗传","volume":"48 7","pages":"741-750"},"PeriodicalIF":0.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148473220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The retrotransposon LINE-1: a double-edged sword in tumorigenesis.","authors":"Lu Tian, Qian Liu, Shan Cen, Xiao-Yu Li","doi":"10.16288/j.yczz.25-289","DOIUrl":"https://doi.org/10.16288/j.yczz.25-289","url":null,"abstract":"<p><p>Transposons, also known as jumping genes, are DNA sequences capable of relocating within or between chromosomes. Long interspersed element-1 (LINE-1), the only autonomously active retrotransposon in the human genome, plays a critical role in maintaining genomic stability through its dynamic regulation. Under normal physiological conditions, the host employs epigenetic and other mechanisms to maintain LINE-1 in a silenced state. However, when this precise regulatory control is disrupted, aberrant LINE-1 activation can lead to insertional mutations, resulting in genomic instability and the development of various genetic disorders and malignant tumors. Recent evidence has demonstrated elevated LINE-1 expression in multiple cancers, such as breast, esophageal, lung, and colorectal cancer, suggesting a close association between LINE-1 dysregulation and tumorigenesis. This review summarizes the multi-layered regulatory network governing LINE-1, encompassing epigenetic modifications, non-coding RNAs, and various host restriction factors. It also explores the molecular mechanisms underlying LINE-1 aberrant activation in the tumor microenvironment and outlines the diverse pathways through which LINE-1 influences tumor development, such as compromising genomic stability, triggering inflammation and immune responses, and participating in cellular immortalization. This review not only provides a theoretical foundation for utilizing LINE-1 as a molecular biomarker in cancer diagnosis but also offers new perspectives for developing novel anti-tumor therapeutic strategies based on LINE-1 regulation.</p>","PeriodicalId":35536,"journal":{"name":"遗传","volume":"48 7","pages":"671-689"},"PeriodicalIF":0.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148473223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulatory mechanism of Pabpc1a during zebrafish vasculogenesis.","authors":"Yu-Qin Hu, Fan Liu, Ying Li, Lu Wang","doi":"10.16288/j.yczz.26-042","DOIUrl":"https://doi.org/10.16288/j.yczz.26-042","url":null,"abstract":"<p><p>Vascular development begins with vasculogenesis during early embryogenesis. This process is controlled by a highly integrated, multi-layered molecular network. However, the role of post-transcriptional regulation in this context remains poorly understood. Cytoplasmic poly(A) binding protein 1a (Pabpc1a<i>)</i> is a key RNA-binding protein that regulates gene expression at the post-transcriptional level and participates in many physiological and pathological processes. Its role in vascular development, however, is still unclear. In this study, we first found that <i>pabpc1a</i> is highly expressed in endothelial cells during the critical window of vasculogenesis. We then generated a <i>pabpc1a</i> knockout model using CRISPR/Cas9. Functional analyses showed that loss of <i>pabpc1a</i> disrupted the expression of genes involved in arterial-venous specification and altered the arterial-to-venous diameter ratio. In contrast, overexpression of <i>pabpc1a</i> effectively rescued the vascular defects. Mechanistically, transcriptomic analysis revealed widespread gene expression changes in endothelial cells lacking <i>pabpc1a</i>. Pathways related to translation, ribosome biogenesis, and energy metabolism were significantly downregulated. These findings suggest that Pabpc1a regulates vasculogenesis by coordinating protein synthesis and metabolic homeostasis. In summary, our study demonstrates Pabpc1a as an essential post-transcriptional regulator during vasculogenesis and provides new insight into the regulatory network governing vascular development.</p>","PeriodicalId":35536,"journal":{"name":"遗传","volume":"48 7","pages":"714-725"},"PeriodicalIF":0.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148473160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of biological age for aging evaluation and its clinical applications.","authors":"Dan-Qing Huang, Jing Guo, Yan Guo, Tie-Lin Yang","doi":"10.16288/j.yczz.26-015","DOIUrl":"https://doi.org/10.16288/j.yczz.26-015","url":null,"abstract":"<p><p>As the global population ages, the development of methods that can accurately quantify individual aging status and overcome the limitations of chronological age assessment has become an important need in aging research and precision medicine. Biological age serves as an important tool for assessing an individual's true physiological aging process and disease risk by integrating multi-omics data and organ-specific biomarkers. In this review, we systematically summarize the development of methods for assessing aging, with a focus on the construction strategies and evolution of aging clocks based on epigenetic, transcriptomic, proteomic, and metabolomic markers. We also discuss emerging approaches for organ-specific aging assessment based on imaging data and the integration of multi-omics data. By synthesizing evidence for the clinical applications of these approaches in the early screening and risk stratification of aging-related diseases, personalized interventions, and health management, we further highlight the importance and translational potential of biological age in precision aging assessment and intervention.</p>","PeriodicalId":35536,"journal":{"name":"遗传","volume":"48 7","pages":"690-700"},"PeriodicalIF":0.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148473168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine learning-based geographical ancestry inference model for the Han Chinese population.","authors":"Shuai-Qi Wang, Chun-Nian Wang, De-Qin Zhang, Lin-Lin Lou, Yi-Ting Ban, Li Jiang, Cai-Xia Li","doi":"10.16288/j.yczz.25-261","DOIUrl":"10.16288/j.yczz.25-261","url":null,"abstract":"<p><p>The Han Chinese population exhibits a complex genetic structure characterized by subtle yet discernible regional differentiation. Elucidating this fine-scale population structure and developing robust models for biogeographical ancestry inference are of great significance for revealing population evolutionary patterns and achieving precise ancestry inference. However, ancestry inference models specifically tailored to the genetic diversity within the domestic Han Chinese population remain scarce. In this study, we analyzed high-density SNP data from 1,229 Han Chinese individuals across eight provinces to investigate the correlation between genetic variation and geographic distribution, and to construct a machine learning-based model for regional ancestry prediction. After stringent quality control (including linkage disequilibrium pruning), we retained 208,193 SNPs for downstream analysis. Principal component analysis (PCA) and ADMIXTURE clustering revealed measurable genetic stratification corresponding to geography, supporting the delineation of seven distinct genetic clusters within the Han population. Leveraging the top principal components as features, we trained and compared multiple classifiers-XGBoost, random forest, and <i>K</i>-nearest neighbors-<i>via</i> five-fold cross-validation on the reference set, with model performance evaluated using both top-rank prediction accuracy and likelihood ratio (LR)-based metrics. The results showed that the PCA-XGBoost model achieved the optimal prediction performance in the reference set, with a first-rank prediction accuracy of 87.66% and an LR-based accuracy of 96.87%. In independent test sets, the PCA-XGBoost model maintained strong performance (first-rank prediction accuracy >85%; LR-based accuracy >95%), demonstrating excellent generalizability and stability. In summary, the PCA-XGBoost predictive model developed in this study demonstrates high efficiency, robustness, and accuracy, offering a reliable methodological tool for research in population genetics and forensic genetics.</p>","PeriodicalId":35536,"journal":{"name":"遗传","volume":"48 7","pages":"726-740"},"PeriodicalIF":0.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148473203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}