遗传最新文献

{"title":"Potential risk proteins for suicide attempts: multi-omics analysis based on European population biobanks.","authors":"Mei-Qi Peng, Bo Xiang","doi":"10.16288/j.yczz.25-201","DOIUrl":"10.16288/j.yczz.25-201","url":null,"abstract":"<p><p>Suicide is defined as an intentional act of ending one's own life. Suicide attempt (SA) is a significant risk factor for suicide death. Research on SA has progressed from socio-psychological perspectives to the molecular and genetic levels. While the biological mechanisms underlying genome-wide association studies (GWAS) identified risk loci remain largely unclear. To investigate the potential risk mechanisms, we constructed a systematic analytic pipeline using brain protein quantitative trait locus (pQTL) datasets (Banner, <i>N</i>=152; ROSMAP, <i>N</i>=376), a brain expression quantitative trait locus (eQTL) datasets (<i>N</i>=452), and SA GWAS summary statistics (<i>N</i>_case=35,786, <i>N</i>_control=779,392). We performed proteome-wide association study (PWAS), Mendelian randomization (MR), Bayesian colocalization analysis, transcriptome-wide association study (TWAS), and multi-marker analysis of genomic annotation (MAGMA) to systematically identify and screen for novel genetically supported candidate proteins related to the biological mechanism of SA in the brain. For functional annotation, we used the GeneMANIA to bulid a functional prediction network integrating co-expression, physical interactions, and pathway colocalization to identify core proteins. PWAS identified three brain proteins whose genetically predicted abundance was significantly associated with SA. Among them, GMPPB was prioritized as putative causal protein, supported by MR analysis (false discovery rate, FDR<0.05) and Bayesian colocalization analysis (posterior probability PPH₄≥0.8). Specifically, higher genetically predicted GMPPB protein levels were associated with increased risk of SA. Although our analyses primarily relied on datasets from European-ancestry populations, the shared genetic architecture across populations and the generalizability of genome-wide data analytical approaches suggest that our findings may still provide useful insights into the biological mechanisms underlying SA and help inform the development of intervention strategies and genetic counseling in Chinese populations.</p>","PeriodicalId":35536,"journal":{"name":"遗传","volume":"48 7","pages":"701-713"},"PeriodicalIF":0.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148473233","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":"A novel strategy to enhance precise targeting of the RNA base editor mxABE.","authors":"Tan Liu, Hui-Jie Jiang, Xue-Lang Wang, Yao-Yao Yu, Fei Wang, Jia-Jia Lin, Hua-Qiang Yang","doi":"10.16288/j.yczz.25-303","DOIUrl":"https://doi.org/10.16288/j.yczz.25-303","url":null,"abstract":"<p><p>Single nucleotide variations (SNVs) represent the most common form of pathogenic mutations in humans, while base editing technology offers an ideal solution for treating such pathogenic variants. RNA editing has become a hotspot in current gene therapy due to its reversible action, which avoids long-term risks by not permanently altering the genome, and the compact size of the editors. Among these, the mini-dCas13X.1-mediated RNA adenine base editing (mxABE) system demonstrates highly efficient RNA base editing; however, it still suffers from non-target nucleotide editing caused by the bystander editing effect, which constitutes a major off-target risk. In this study, by deleting the nucleotide opposite the non-target adenosine in the sgRNA sequence, we effectively reduced the bystander editing effect of the mxABE system. <i>In vitro</i> results showed that this strategy successfully controlled the bystander editing rate below 5% while maintaining highly efficient on-target editing of approximately 70%. In a murine model of DMD (Duchenne muscular dystrophy), a single administration of AAV (adeno-associated virus)-delivered mxABE system demonstrated significant therapeutic efficacy in the tibialis anterior muscle, with successful elimination of off-target adenosine bystander editing. This study provides a novel precision-targeting strategy for treating monogenic genetic diseases using the mxABE RNA editing system.</p>","PeriodicalId":35536,"journal":{"name":"遗传","volume":"48 6","pages":"628-637"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148273225","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":"SNP density impact on kinship inference and IBS-machine learning optimization.","authors":"Lv Dai, Zi-Chen Tang, Zhen Jia, Li Jiang, Chuan-Tong Zhao, Zhi-Yuan Zhao, Wen-Ting Zhao, Cai-Xia Li","doi":"10.16288/j.yczz.25-287","DOIUrl":"https://doi.org/10.16288/j.yczz.25-287","url":null,"abstract":"<p><p>In recent years, multiple panels containing varying numbers of single nucleotide polymorphisms (SNPs) have been reported in forensic genetics for kinship inference. However, systematic exploration of the impact of SNP number on inference performance and the application of machine learning algorithms remains lacking. Therefore, we evaluated the impact of SNP number on kinship inference performance and the optimization effects of machine learning methods on the identity-by-state (IBS) algorithm. We constructed multiple SNP panels with SNP numbers ranging from 15,476 to 20,838, and evaluated the performance of the likelihood ratio (LR) method and the IBS algorithm for kinship inference under different SNP numbers based on simulated pedigrees. After selecting the optimal SNP panel, we validated it using real pedigrees and further combined the IBS algorithm with machine learning methods to enhance inference performance. Our results showed that for the LR method, the sensitivity in inferring sixth and seventh degree kinships exhibited a significant positive correlation with SNP number. For the IBS algorithm, although the sensitivity in inferring fourth to seventh degree kinships showed a significant positive correlation with SNP number, the actual improvement was limited (only 0.5%~2.2% increase). Based on these results, we determined the optimal panel containing 20,838 SNPs (21K panel). The 21K panel based on the LR method could accurately infer kinships within sixth degree (with a sensitivity of 93.65% for sixth degree kinship inference), and the 21K panel based on the IBS algorithm could accurately infer kinships within third degree (with a sensitivity of 86.79% for third degree kinship inference). After combining the IBS algorithm with machine learning, the sensitivity for fourth degree kinship inference improved from 69.10% to 87.66%, the sensitivities for fifth and sixth degree kinships improved from 38.03% and 21.41% to 48.75% and 37.80%, respectively.</p>","PeriodicalId":35536,"journal":{"name":"遗传","volume":"48 6","pages":"570-588"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148273287","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":"System construction for sui generis right of digital sequence information on genetic resources in China.","authors":"Wen-Fei Zhang, Fei Yang, Xian-Jie Zhou","doi":"10.16288/j.yczz.25-305","DOIUrl":"10.16288/j.yczz.25-305","url":null,"abstract":"<p><p>Digital sequence information on genetic resources plays an increasingly vital role in research on improving crop yields and reducing impacts of disease. However, there are still problems such as the imperfect rights' protection system, which hinders the protection and sustainable use of genetic resources and constrains the realization of the fair and equitable benefit-sharing objectives established by the Convention on Biological Diversity. To address these issues, we first define the connotation and legal nature of digital sequence information on genetic resources. Then, we elaborate how digital sequence information on genetic resources aligns with the modern intellectual property systems. For digital sequence information on genetic resources to be protected by intellectual property rights, we analyze the substantive conditions of novelty and practicality as well as the procedural conditions of registration. Building on this analysis, we identify the limitations of existing intellectual property frameworks in accommodating digital sequence information on genetic resources, and propose a normative structure of sui generis right of digital sequence information on genetic resources. The subjects of sui generis right are divided into two levels, i.e. static right attributed to the state, and dynamic right exercised by the farmer collective of specific communities and the uploaders of digital sequence information, exercising respectively in accordance with different functions. The contents of sui generis right include the informed consent right, the source indication right and benefit-sharing right based on licensing. Furthermore, we propose to establish the limitations on sui generis right, such as restriction on scope of application, compulsory licensing and protection periods. This framework established here is of great significance for achieving the balance of rights and interests, promoting innovation in plant breeding and protecting genetic diversity.</p>","PeriodicalId":35536,"journal":{"name":"遗传","volume":"48 6","pages":"557-569"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148273279","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":"Construction and implementation of an ICF-based integrated teaching model for genetic disease severity assessment.","authors":"Qing-Li Quan, Mei-Xing Yu, Hai-Ou Jiang","doi":"10.16288/j.yczz.26-005","DOIUrl":"https://doi.org/10.16288/j.yczz.26-005","url":null,"abstract":"<p><p>To enhance the competency of clinical medicine students in evaluating the severity of genetic disorders, this study first modularized an assessment of genetic diseases severity based on the World Health Organization's International Classification of Functioning, Disability and Health (ICF) framework. Then, this modular teaching framework was applied in teaching instruction. During the Medical Genetics course, the 2024 clinical medicine cohort at Hunan University of Medicine were clustered into a experimental group (6 classes, 203 students) and a control group (7 classes, 235 students) randomly. The experimental group engaged in the ICF-based module in the case analysis of genetic diseases, while students in the control group followed the traditional teaching methods. Learning outcomes were evaluated by analyzing the student-written genetic disease severity evaluation reports. Results demonstrated that students in the experimental group achieved significantly higher scores on their assessment reports (73.33±7.16) compared to the control group (64.79±5.45), with a statistically significant difference (<i>t</i>=13.87, <i>P</i><0.001). Furthermore, textual analysis further revealed that reports from the experimental group contained a significantly higher frequency of keywords related to patient psychology, social functioning, and environmental factors, indicating a broader focus on the patients and more comprehensive and in-depth understanding of the patient's situation. These findings suggest that the ICF-based modular teaching framework significantly improves medical students' ability to conduct individualized assessments of genetic diseases and effectively fosters their humanistic care. This study provides an actionable and scalable teaching practice pathway for cultivating clinical genetic counseling professionals.</p>","PeriodicalId":35536,"journal":{"name":"遗传","volume":"48 6","pages":"648-656"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148273216","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 p53 R267W mutation intervenes p21-mediated cell cycle arrest and promotes proliferation and migration of lung cancer cells.","authors":"Jia-Ning Zhao, Jin-Zheng Wu, Shu-Bing Zhang","doi":"10.16288/j.yczz.25-222","DOIUrl":"https://doi.org/10.16288/j.yczz.25-222","url":null,"abstract":"<p><p>Pathogenic germline variants in <i>TP53</i> constitute the central etiological driver of hereditary tumor predisposition disorders syndromes. The oncogenic mechanisms of hotspot mutations in the DNA-binding domain of p53 are well-established. However, the functional consequences of non-hotspot missense mutations remain incompletely understood. In this study, we characterized the molecular pathogenesis and clinical significance of the p53 non-hotspot mutation p.Arg267Trp (p.R267W). In addition, evolutionary conservation analysis, structural prediction, and functional assays including CCK-8 cell proliferation, clonogenic assay, Transwell migration, wound healing assay, qPCR, Western blot, single luciferase reporter assay, and flow cytometry techniques were performed to assess the impact of R267W on <i>TP53</i> target gene (<i>CDKN1A</i>) regulation and tumor-suppressive phenotypes (proliferation, colony formation, migration) in non-small cell lung cancer models (A549/NCI-H1299). Experiments confirmed that the mutant does not affect the p53 protein stability. The impairment of protein function is hypothesized to result from the disruption of the DNA-binding domain conformation. Experimental evidence suggested that the mutant <i>TP53</i> exhibited significantly reduced transcriptional activity (<i>P</i><0.001), resulting in a concomitant reduction in <i>CDKN1A</i> mRNA expression and diminished cell cycle arrest capability when compared to wild type. At the tumor-suppressive functional level, the R267W mutant significantly reduced inhibition rates of non-small cell lung cancer cell proliferation, colony formation, and migration relative to wild type (<i>P</i><0.05). This study reveals that the R267W variant drives cell cycle dysregulation and malignant phenotypes in lung cancer by disrupting <i>TP53</i>'s transcriptional functions. These findings establish a molecular basis for the pathogenic classification of <i>TP53</i> variants of uncertain clinical significance.</p>","PeriodicalId":35536,"journal":{"name":"遗传","volume":"48 6","pages":"589-600"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148273292","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":"Role of <i>broad</i> in intestinal stem cells of adult <i>Drosophila</i>.","authors":"Chang-Hao Ji, Nuan Wang, Xin-Yang Wang, Mei-Zhu Zhang, Jin Sun","doi":"10.16288/j.yczz.26-004","DOIUrl":"https://doi.org/10.16288/j.yczz.26-004","url":null,"abstract":"<p><p>Ecdysone signaling is necessary for maintaining intestinal homeostasis in adult <i>Drosophila melanogaster</i> by promoting stem cell proliferation and differentiation. However, the role of its downstream target <i>broad</i> (<i>br</i>) in this process remains largely unclear. Here, this study demonstrates that <i>br</i> is required for the maintenance of intestinal stem cells (ISCs) and intestinal injury repair. Clonal analysis shows that <i>br</i> regulates both the proliferation and differentiation of ISCs. Knockdown of <i>br</i> severely impairs the differentiation of stem cells into enterocytes (ECs), whereas overexpression of <i>br</i> promotes ECs differentiation. Further analysis reveals that <i>br</i> knockdown reduces Jak/STAT signaling activity in ISCs. Moreover, upregulating the activity of Jak/STAT or EGFR signaling significantly rescues the <i>br</i> knockdown phenotype. These results suggest that <i>br</i> may regulate the proliferation and differentiation of ISCs through Jak/STAT and EGFR signaling in adult <i>Drosophila</i>. This study highlights the critical role of <i>br</i> in adult <i>Drosophila</i> ISCs and provides a preliminary exploration of its underlying mechanism.</p>","PeriodicalId":35536,"journal":{"name":"遗传","volume":"48 6","pages":"601-613"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148273222","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":"Identification and prenatal genetic testing of pathogenic variants in a case of myoclonus-dystonia syndrome.","authors":"Han-Xiao Ou, Xia Zhou, Li-Ya Chen, Wei Cai, Wen-Mao Zhang, Qun Zhu, Hong-Xiang Mu","doi":"10.16288/j.yczz.25-235","DOIUrl":"10.16288/j.yczz.25-235","url":null,"abstract":"<p><p>Myoclonus-dystonia syndrome (MDS) is a movement disorder syndrome characterized primarily by myoclonus as the core feature. In this study, we reported a case of MDS with myoclonus as the prominent feature, which was accompanied by learning disability and special face. We then used copy number variation sequencing (CNV-seq), whole exome sequencing (WES) and Sanger sequencing to verify the MDS related genes of the patient and his family members. We found that the patient carried a heterozygous mutation of <i>SGCE</i> gene c.731dup (p.Asn244Lysfs*6) related to MDS, which inherited from his father. It was the first reported new mutation at home and abroad. And we confirmed <i>via</i> prenatal diagnosis that his fetus also had a heterozygous mutation of <i>SGCE</i> gene c.731dup (p.Asn244Lysfs*6). In addition, we also found that there was a 1.40 Mb repeat fragment at p23.1 on chromosome 8 of the patient, which partially overlapped with 8p23.1 repeat syndrome. It is speculated that it may be related to the learning disability and special facial phenotype of the patient, and it was a <i>de novo</i> variant. This study not only clarified the etiology of the patient's myoclonus, but also enriched the genetic variation database of <i>SGCE</i> gene by the newly discovered heterozygous heterozygous site of c.731dup (p.Asn244Lysfs*6) of <i>SGCE</i> gene, which was helpful to improve the clinician's awareness of diagnosis of MDS and provide guidance for the patient's fertility.</p>","PeriodicalId":35536,"journal":{"name":"遗传","volume":"48 6","pages":"638-647"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148273211","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":"Functional study of the soybean rapid alkalinization factor <i>GmRALF34s</i> in response to saline-alkali stress.","authors":"Man-Ting Zhang, Zi-Hao Lu, Min-Qi Nie, Yu-Xiang Tan, Qi-Mei Liang, Mao-Yan Luo, Yong-Dong Dai, Jin-Tao Li, Wei Chen, Zi-Mei Chen, Jia-Xian He, Meina Li","doi":"10.16288/j.yczz.25-349","DOIUrl":"https://doi.org/10.16288/j.yczz.25-349","url":null,"abstract":"<p><p>China's soybean supply is heavily dependent on international markets, making it an urgent task to enhance domestic self-sufficiency to ensure food security. Data from the national soil census indicate that China possesses approximately 500 million mu of saline-alkali soil resources, of which about 200 million mu have potential for agricultural development. Against the backdrop of tight arable land resources, developing new soybean varieties tolerant to saline-alkali conditions represents a strategic initiative to effectively utilize saline-alkali land, expand cultivation areas, and address the challenge of soil salinization. Rapid alkalinization factors (RALFs) are a class of plant small peptides that act as ligands, initiating downstream signaling by binding to plasma membrane receptor complexes, thereby coordinating plant growth, development, and stress responses. However, the specific molecular mechanisms by which RALF peptides mediate responses to saline-alkali stress in important crops such as soybean remain unclear. Through expression profiling analysis of the soybean RALF family, combined with transcriptome data under alkaline salt treatment, this study identified two homologs of <i>Arabidopsis thaliana AtRALF34</i>, designated <i>GmRALF34a</i> and <i>GmRALF34b</i>, which are predominantly expressed in roots and whose expression is significantly suppressed following alkaline salt treatment. Using gene editing technology, we generated <i>Gmralf34ab</i> double mutants, which exhibited enhanced sensitivity to alkaline salt stress. In contrast, no significant differences were observed between the mutant and wild type plants under neutral salt stress. Field phenotypic characterization further demonstrated that the mutants showed significant reductions in agronomic traits, including plant height, node number, and yield per plant. In conclusion, this study preliminarily reveals that <i>GmRALF34s</i> play an important role in soybean response to alkaline salt stress and adaptation to saline-alkaline environments, provides valuable genetic materials for further elucidating their molecular mechanisms and establishing a theoretical and material foundation for breeding salt-alkali tolerant soybean varieties.</p>","PeriodicalId":35536,"journal":{"name":"遗传","volume":"48 6","pages":"614-627"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148273231","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":"Application and potential value of genotype imputation techniques in ancient DNA research.","authors":"Wen-Qi Wei, Da-Wei Cai","doi":"10.16288/j.yczz.25-166","DOIUrl":"10.16288/j.yczz.25-166","url":null,"abstract":"<p><p>Ancient DNA research plays a pivotal role in reconstructing history and understanding biological evolution. Modern genotype imputation techniques, which leverage reference panels to predict missing genotypes, have emerged as powerful tools for enhancing genetic information retrieval from ancient DNA. In this review, we examine state-of-the-art computational tools and algorithms-including GLIMPSE, Beagle, and QUILT-that enable more comprehensive analysis of genetic architecture and evolutionary patterns in ancient humans and animals. While analytical accuracy can be affected by variables such as sampling strategies and reference panel composition, the field shows tremendous potential for growth. Key future directions include: (1) algorithmic refinements, (2) computational efficiency improvements, (3) integration with emerging technologies, and (4) expansion into novel research domains. These advances are expected to offer new perspectives for advancing ancient DNA research and understanding ancient life systems.</p>","PeriodicalId":35536,"journal":{"name":"遗传","volume":"48 5","pages":"471-482"},"PeriodicalIF":0.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147964790","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}