Gene Reports最新文献

{"title":"Disruption of LINC00265/miR-101-3p axis using siRNA suppresses growth and promotes apoptosis in laryngeal cancer cells","authors":"Mohaddese Maghsudlu ,&nbsp;Masoumeh Razipour ,&nbsp;Elham Ghadami ,&nbsp;Ebrahim Karimi ,&nbsp;Elia Damavandi ,&nbsp;Negin Saeedi ,&nbsp;Farzad Yazdani Bioki ,&nbsp;Majid Kabuli ,&nbsp;Mohsen Ghadami","doi":"10.1016/j.genrep.2025.102405","DOIUrl":"10.1016/j.genrep.2025.102405","url":null,"abstract":"<div><h3>Background</h3><div>Laryngeal cancer is a prevalent malignancy of the head and neck, often associated with poor prognosis due to late diagnosis and therapeutic resistance. Emerging evidence highlights the important role of long non-coding RNAs (lncRNAs) in cancer progression, including LINC00265, which has been implicated in promoting tumor growth and metastasis in various cancers. Conversely, miR-101 functions as a tumor suppressor by targeting oncogenic pathways. Understanding the regulatory interaction between LINC00265 and miR-101 can provide new insights into disease biology.</div></div><div><h3>Methods</h3><div>We evaluated LINC00265 expression in 30 paired LSCC and adjacent normal tissues using qRT-PCR, which was followed by analyzing its correlation with clinicopathological features. To investigate LINC00265 functional effects, HN5 cells were transfected with LINC00265-specific siRNA, and afterward, cell viability and apoptosis were assessed through MTT assay and Annexin V/PI flow cytometry, respectively.</div></div><div><h3>Results</h3><div>Our results showed that LINC00265 was significantly overexpressed in LSCC tissues (2.52-fold increase, <em>p</em> &lt; 0.0129), which was correlated with larger tumor size and lymph node metastasis. Moderate diagnostic accuracy for metastasis detection was demonstrated by ROC analysis (AUC = 0.74, <em>p</em> = 0.0276). Moreover, the knockdown of LINC00265 in HN5 cells significantly reduced cell viability by 30 %, and increased apoptosis up to 36.03 % potentially through upregulation of miR-101 (1.53-fold, <em>p</em> = 0.0012).</div></div><div><h3>Discussion</h3><div>Our study proposes that LINC00265 might exert an oncogenic effect in LSCC by promoting tumor progression, potentially through miR-101 suppression. Its association with metastasis and larger tumor size suggests clinical relevance as a prognostic biomarker. The knockdown of LINC00265 demonstrated anti-proliferative and pro-apoptotic effects that could suggest its therapeutic potential for LSCC treatment.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"42 ","pages":"Article 102405"},"PeriodicalIF":0.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145786453","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":"Exome sequencing reveals a novel de novo ARHGAP31 frameshift variant in a neurodevelopmental disorder: Structural and functional insights into RhoGAP domain loss","authors":"Jalal Gharesouran ,&nbsp;Mohammad Reza Asadi ,&nbsp;Samira Behroozi ,&nbsp;Maryam Rezazadeh ,&nbsp;Soudeh Ghafouri-Fard","doi":"10.1016/j.genrep.2025.102345","DOIUrl":"10.1016/j.genrep.2025.102345","url":null,"abstract":"<div><div>ARHGAP31 is a GTPase activating protein that inactivates Rac1 and Cdc42 by promoting their conversion from the GTP to GDP bound state. Pathologic variants in <em>ARHGAP31</em> are primarily associated with Adams-Oliver syndrome (AOS), a congenital disorder characterized by aplasia cutis congenita (ACC) and terminal transverse limb defects (TTLDs), attributed to disrupted Rho GTPase signaling. In this study, exome sequencing and bioinformatic analysis were employed to investigate a 6-year-old male presenting with craniofacial anomalies (high palate, dental malalignment), developmental delay (motor and speech), and gastrointestinal dysmotility (feeding difficulties, constipation) notably without ACC or TTLDs. Trio exome sequencing revealed a heterozygous de novo frameshift variant in <em>ARHGAP31</em> (NM_020754.4:c.732del, p.(Met245Ter)), absent from population databases (gnomAD, dbSNP) and both parental genomes. In silico predictions (MutationTaster, SWISS-MODEL) suggested a pathogenic effect (probability: 0.99), with nonsense-mediated decay (NMD) and truncation of the RhoGAP domain critical for cytoskeletal regulation. The variant's proximal truncation site likely disrupts autoinhibitory regulation, enhancing RhoGAP activity and impairing Cdc42/Rac1 signaling. Despite parental consanguinity, the de novo variant highlights the diagnostic value of trio sequencing in consanguineous families. Moreover, until now only gain-of-function mutation of <em>ARHGAP31</em> was found to be associated with AOS, while this article reports a brand-new loss-of-function mutation. Overall, these findings support the existence of a novel ARHGAP31-related neurodevelopmental disorder distinct from AOS, expanding the allelic and phenotypic spectrum associated with this gene.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"41 ","pages":"Article 102345"},"PeriodicalIF":0.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145265510","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":"Comprehensive genomic analysis of the novel PAX6:c.194G>A (p.Gly65Glu) mutation: Highlighting a potential association with aniridia and autism spectrum disorder","authors":"Mohammad Salimi Asl ,&nbsp;Yousef Jafari Abarghan ,&nbsp;Narjes Bakhtari ,&nbsp;Sepideh Shohani ,&nbsp;Mina Mohammadi Sarband ,&nbsp;Sorayya Ghasemi","doi":"10.1016/j.genrep.2025.102353","DOIUrl":"10.1016/j.genrep.2025.102353","url":null,"abstract":"<div><h3>Background</h3><div>Aniridia is a congenital eye disorder characterized by a partially or completely missing iris, frequently accompanied by other eye abnormalities. Communication difficulties, social interaction issues, and repetitive behaviors are hallmarks of autism spectrum disorder (ASD), a neurodevelopmental disorder. Identifying a causal gene(s) that is involved in aniridia and ASD in a patient is the goal of this research.</div></div><div><h3>Methods</h3><div>Genetic counseling, pedigree analysis, and a thorough clinical evaluation were performed on a 9-year-old female patient who presented with congenital aniridia and ASD. Karyotyping, Comparative Genomic Hybridization (CGH)-array, Whole-Exome Sequencing (WES), Sanger sequencing, and STR-based paternity testing were performed. In silico structural modeling was done using I-TASSER, and PyMOL 3.1.1 was used to find putative genetic variants.</div></div><div><h3>Results</h3><div>WES identified a novel de novo heterozygous point mutation, c.194G&gt;A (p.Gly65Glu), in the <em>PAX6</em> gene. Sanger sequencing confirmed this mutation, which was not discovered in population databases. STR-based paternity testing verified its de novo mutation. In silico tools (PolyPhen-2: 0.998; SIFT: 0.01; CADD: 35.0) predicted a deleterious effect.</div></div><div><h3>Conclusions</h3><div>This study provides the first report of a novel de novo <em>PAX6</em>:c.194G&gt;A (p.Gly65Glu) mutation associated with aniridia and ASD. The findings highlight the pleiotropic role of <em>PAX6</em> and support the utility of WES in detecting rare variants in complex phenotypes. Functional studies are necessary to confirm the pathogenic mechanism.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"41 ","pages":"Article 102353"},"PeriodicalIF":0.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145412675","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":"Estimating genetic basis of venous thromboembolism (VTE) risk in Indian population: A case control study","authors":"Babita Kumari ,&nbsp;Sunanda Arya ,&nbsp;Rashi Khare ,&nbsp;Iti Garg ,&nbsp;Prince ,&nbsp;Rajneesh Kumar Joshi ,&nbsp;Rajiv Kumar ,&nbsp;Swati Srivastava","doi":"10.1016/j.genrep.2025.102379","DOIUrl":"10.1016/j.genrep.2025.102379","url":null,"abstract":"<div><div>Venous thromboembolism (VTE) is a potentially fatal, complex multifactorial disease involving acquired, clinical and genetic risk factors. VTE results in formation of abnormal blood clots affecting 1–3 individuals per thousand in general population. Etiology to VTE is largely attributed to presence of genetic risk factors such as increased activity of coagulation factors and decreased expression of natural anti-coagulants. In such a scenario, it becomes utmost important to have a genetic predictive tool based on which the individuals susceptible to VTE pre-disposition could be screened and prophylactic measures could be taken to mitigate morbidity and mortality. Present study screened sixteen single nucleotide polymorphism (SNP) markers in blood coagulation and anti-coagulation genes. A total of 89 VTE patients and 116 age-matched healthy controls were genotyped using TaqMan-based SNP real-time PCR assays targeting coagulation and anticoagulation pathway genes. Genotypic distribution of each SNP was compared between cases and controls using chi-square (χ²) and Student's <em>t</em>-tests. Odds ratios (ORs) with 95 % confidence intervals (CIs) were calculated to assess VTE risk. A <em>p</em>-value &lt;0.05 was considered statistically significant. Genetic analysis revealed that variants in F7 (rs6046) and F13 (rs6003) were associated with increased risk of venous thromboembolism (VTE), whereas changes in F13 and F10 (rs321175) appeared protective. Among anticoagulant genes, a PLG rs4252125 variant showed strong risk association, while variations in COX2 rs5788 and COX1 rs3842788 showed protective associations. Other tested variants showed no significant association with VTE. This study identifies both novel and established SNPs associated with VTE risk in the Indian population, highlighting the importance of genetic screening for personalized risk prediction.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"41 ","pages":"Article 102379"},"PeriodicalIF":0.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145525822","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":"Association of the MTHFR and VDR polymorphisms with cognitive impairment and affective symptoms in alcohol-dependent inpatients during abstinence","authors":"Danil Peregud ,&nbsp;Valeria Baronets ,&nbsp;Maxim Viksna ,&nbsp;Olga Pavlova ,&nbsp;Konstantin Pavlov","doi":"10.1016/j.genrep.2025.102323","DOIUrl":"10.1016/j.genrep.2025.102323","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Alcohol dependence is associated with cognitive impairment often accompanied by depression and anxiety with a potential of partial recovery during abstinence. However, the corresponding genetic markers remain elusive. The goal of this study was to examine an association of the rs1801133 single nucleotide polymorphism (SNP) in the methylenetetrahydrofolate reductase (MTHFR) gene as well as rs7975232 and rs1544410 SNPs in the vitamin D receptor (VDR) gene with cognitive function and affective symptoms during the abstinence period after alcohol withdrawal.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;One hundred thirty-two alcohol-dependent inpatients admitted for alcohol withdrawal syndrome treatment were enrolled in the study. The Montreal Cognitive Assessment (MoCA) tool was used to assess cognitive impairment. The Beck Depression Inventory (BDI) and State-Trait Anxiety Inventory (STAI) subscale-1 were administered to assess the severity of affective symptoms. Psychometric testing was performed on the 7&lt;sup&gt;th&lt;/sup&gt; and 21&lt;sup&gt;st&lt;/sup&gt; days of abstinence. MTHFR rs1801133 (also known as C677T or Ala222Val), VDR rs7975232 (&lt;em&gt;Apa&lt;/em&gt;I) and VDR rs1544410 (&lt;em&gt;Bsm&lt;/em&gt;I) SNPs were genotyped using real-time PCR. Repeated measures ANOVA and general linear models were used to test the effects of each SNP separately and their interactions on BDI, STAI-1 or MoCA scores.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Carriers of the MTHFR SNP rs1801133 A allele had an earlier onset age of problem drinking and consumed a higher amount of alcohol within three months before the study as compared with the GG genotype carriers. The VDR SNPs did not associate with any drinking behavior parameters. Neither MTHFR rs1801133 nor VDR rs7975232 and VDR rs1544410 as single group factors influenced improvement of cognitive performance and decrease of affective symptoms over the course of abstinence. However, analysis of pairwise interactions demonstrated that both MTHFR rs1801133 × VDR rs7975232 and MTHFR rs1801133 × VDR rs1544410 had a significant effect on BDI, but not on MoCA or STAI-1 scores during abstinence. Carriers of both MTHFR rs1801133 GG genotype and VDR rs7975232 C allele had significantly higher BDI scores on the 7th day of abstinence as compared with carriers of the MTHFR rs1801133 A allele and VDR rs7975232 C allele. Moreover, carriers of the MTHFR rs1801133 A allele having the VDR rs1544410 CC genotype had significantly lower BDI scores on the 7th day of abstinence as compared with carriers of the MTHFR rs1801133 A allele having the VDR rs1544410 T allele.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;According to the present data the MTHFR rs1801133, VDR rs7975232 and rs1544410 SNPs alone had no effect on cognitive impairment and affective symptoms during the alcohol abstinence period. However, the MTHFR SNP rs1801133 interacted with both VDR SNPs rs7975232 and rs1544410 in regard to depression levels during the earlier period of alcohol abstine","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"41 ","pages":"Article 102323"},"PeriodicalIF":0.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144867057","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":"Phylogenetic structure and paternal migration history of Sichuan Bouyei people revealed by Y-chromosomal STRs","authors":"Guang-Yao Fan ,&nbsp;En-Na Wang ,&nbsp;Jia-Xin Han ,&nbsp;Xin-Ying Yu ,&nbsp;An-Ying Zheng ,&nbsp;Ying Zhu","doi":"10.1016/j.genrep.2025.102342","DOIUrl":"10.1016/j.genrep.2025.102342","url":null,"abstract":"<div><div>This study investigates the phylogenetic structure and demographic history of the Sichuan Bouyei people. Genetic profiles of 37 Y-chromosomal short tandem repeat (STR) loci among 425 Bouyei males from eight regions in Sichuan Province were analyzed. Along with published datasets, multidimensional scaling plots, principal component analysis, and phylogenetic reconstruction were conducted on both an Asia-wide and national scale. Genetic stratification in the studied populations was influenced by linguistic and geographic distribution patterns. Significant genetic differentiation was observed between two predominant Bouyei groups from the counties of Ningnan and Muli. Machine learning-based category prediction was performed among contemporary Bouyei and non-Bouyei individuals using the Linear Discriminant Analysis (LDA) method. The results of the LDA indicated a deep fusion between Tai-Kadai-speaking and Hmong-Mien-speaking populations. The timing of population differentiations was estimated using BATWING. Furthermore, the migration rate between the Sichuan Bouyei and other populations was inferred using coalescence theory in the Migrate-n program. The migration models and directions were evaluated, revealing gene flow of Bouyei people from the Sichuan Muli to Vietnam. The data presented here for the Sichuan Bouyei people will be useful in establishing a more comprehensive Y-STR database, and enrich our understanding of the patrilineal history of Tai-Kadai-speaking peoples in China.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"41 ","pages":"Article 102342"},"PeriodicalIF":0.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145104788","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":"Genomic architecture of skeletal malocclusions: Implications for precision orthodontics - Narrative review","authors":"Katarzyna Chojnacka ,&nbsp;Marcin Mikulewicz","doi":"10.1016/j.genrep.2025.102347","DOIUrl":"10.1016/j.genrep.2025.102347","url":null,"abstract":"<div><h3>Background</h3><div>Genetic variants, particularly single-nucleotide polymorphisms (SNPs), have been linked to craniofacial growth, dentoalveolar development, and skeletal remodeling through core pathways that govern morphogenesis (e.g., FGF/FGFR, WNT/β-catenin, TGF-β/BMP, and the GH/IGF axis). Interethnic differences in allele frequencies and effect sizes indicate ancestry-specific architecture. Multiple candidate genes and loci related to skeletal Class II/III malocclusion have been reported across genome-wide association studies (GWAS) and candidate-gene analyses, including signals at GHR/IGF1, FGFR2, RUNX2, WNT3A, MSX1, and GLI2.</div></div><div><h3>Aim</h3><div>To collate and critically appraise current genetic evidence on skeletal malocclusions and to identify a functionally supported subset of SNPs relevant to precision orthodontic care. Given cohort heterogeneity and ancestry-specific effects, loci labeled as higher-confidence were prioritized when replication (where available), biological plausibility, and clinical association converged. Here, a functional SNP denotes a variant with experimental or expression evidence for a biological effect on gene regulation, protein function, or development.</div></div><div><h3>Methods</h3><div>Narrative review with a structured search of PubMed/Scopus (last search May 5, 2025). Two complementary approaches were applied: (i) an annotation table linking genotype, phenotype, putative mechanism, zygosity, and references; and (ii) an allele-phenotype matrix stratified by ancestry (Asian, European, admixed).</div></div><div><h3>Results</h3><div>Of approximately 95 reported SNPs screened, 38 met the predefined criteria (including replication where available, functional relevance to craniofacial development, and clinical association with prognathism and/or maxillary deficiency). Replication remains limited for several loci. The resulting set provides a pragmatic basis for risk stratification, not deterministic prediction. From this 38-SNP higher-confidence set, we selected an illustrative 11-SNP subset to prototype PRS-Ortho v1.</div></div><div><h3>Conclusions</h3><div>This narrative review synthesizes evidence from over 70 peer-reviewed studies and presents 38 functionally supported SNPs currently most relevant to craniofacial growth. These data support the personalization of diagnosis, treatment planning, and prognosis in precision orthodontics, while underscoring the need for multi-ethnic replication and prospective evaluation before routine clinical testing. An 11-SNP subset (PRS-Ortho v1) is provided as a prototype for illustrative, unweighted scoring.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"41 ","pages":"Article 102347"},"PeriodicalIF":0.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145216391","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":"Temporal expression patterns of SnRK1 and WRKY3 defense genes reveal cultivar-specific responses to tomato curly stunt virus infection","authors":"Antzel Theron ,&nbsp;Farhahna Allie","doi":"10.1016/j.genrep.2025.102373","DOIUrl":"10.1016/j.genrep.2025.102373","url":null,"abstract":"<div><div>Tomato curly stunt virus (ToCSV) significantly impacts tomato production globally, yet the molecular mechanisms underlying cultivar-specific resistance responses remain poorly understood. We investigated the temporal expression of two key defense-related genes, Sucrose Non-Fermenting 1-Related Protein Kinase 1 (<em>SnRK1</em>) and WRKY transcription factor 3 (<em>WRKY3</em>), across four tomato cultivars with varying susceptibility to ToCSV: susceptible (Rooikhaki, Moneymaker), tolerant (NIL396), and resistant (ESTY). Using quantitative real-time PCR, we analyzed gene expression at 8, 15, and 35 days post-infection, representing early infection, symptom onset, and systemic viral movement stages. Viral quantification revealed distinct accumulation patterns, with susceptible cultivars showing 283–440 % increases in viral load between 15 and 35 dpi, while the tolerant cultivar maintained stable levels and the resistant cultivar remained undetectable. <em>SnRK1</em> expression patterns differed between cultivars: susceptible lines showed initial downregulation (15 dpi) followed by upregulation (35 dpi), while the resistant cultivar exhibited consistent downregulation. <em>WRKY3</em> displayed complex temporal patterns, with most cultivars showing early upregulation followed by late-stage downregulation, except the resistant cultivar, which maintained downregulation throughout. These results provide the first comparative temporal analysis of defense gene expression in the tomato-ToCSV pathosystem and suggest that resistance mechanisms involve distinct regulatory strategies rather than simple gene activation patterns.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"41 ","pages":"Article 102373"},"PeriodicalIF":0.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145462417","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":"Association of the RNASE9 c.1+1G>A splice site variant with decreased sperm motility in Japanese men","authors":"Shinichiro Saeki ,&nbsp;Junko Otsuki ,&nbsp;Noritoshi Enatsu ,&nbsp;Xingqiang Wei ,&nbsp;Naoto Mukaida ,&nbsp;Ryota Okamoto ,&nbsp;Saori Yoshimura ,&nbsp;Keisuke Okada ,&nbsp;Koji Chiba ,&nbsp;Shoji Kokeguchi ,&nbsp;Toshiroh Iwasaki ,&nbsp;Yasuhiro Fujiwara ,&nbsp;Mikiya Nakatsuka ,&nbsp;Tetsuo Kunieda ,&nbsp;Masahide Shiotani","doi":"10.1016/j.genrep.2025.102366","DOIUrl":"10.1016/j.genrep.2025.102366","url":null,"abstract":"<div><div>This study aims to investigate the role of the <em>RNASE9</em> gene mutation (c.1 + 1G &gt; A) in male infertility, specifically focusing on its impact on sperm motility in patients with asthenozoospermia. Despite known genetic causes for azoospermia, the genetic basis of asthenozoospermia remains poorly understood. Given that <em>RNASE9</em> is specifically expressed in the epididymis, where sperm maturation occurs, we hypothesized that mutations in <em>RNASE9</em> might influence post-testicular sperm maturation. Whole-exome sequencing (WES) was performed on 20 Japanese patients with abnormal semen parameters to identify high-impact genetic variants. Variants were filtered based on allele frequencies in the 1000 Genomes Phase 3 East Asian (EAS) population and the Japanese 38KJPN database. <em>RNASE9</em> was selected for further analysis, and the presence of the c.1 + 1G &gt; A variant was confirmed in a cohort of 71 patients via Sanger sequencing. Sperm motility and other semen parameters were evaluated, and allele frequencies in asthenozoospermic, azoospermic, and normospermic groups were compared. The allele frequency of the <em>RNASE9</em> (c.1 + 1G &gt; A) variant was significantly higher in asthenozoospermic patients than in individuals with normal semen parameters (<em>p</em> = 0.022), while no significant difference was found in azoospermic patients. This suggests that the <em>RNASE9</em> variant primarily affects sperm motility rather than sperm production. The <em>RNASE9</em> (c.1 + 1G &gt; A) mutation may contribute to reduced sperm motility in humans, likely impacting post-testicular sperm maturation. The findings provide new insights into the genetic factors affecting sperm motility, particularly in asthenozoospermia.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"41 ","pages":"Article 102366"},"PeriodicalIF":0.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145462425","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":"Detection of Epstein-Barr virus coinfections based on LMP-1 gene diversity obtained by the high-throughput sequencing","authors":"Marija Rozman ,&nbsp;Ana Planinić ,&nbsp;Kristian Bodulić ,&nbsp;Dijana Škorić ,&nbsp;Paola Gršković ,&nbsp;Anita Stojanović Marković ,&nbsp;Petra Korać ,&nbsp;Snježana Židovec-Lepej","doi":"10.1016/j.genrep.2025.102369","DOIUrl":"10.1016/j.genrep.2025.102369","url":null,"abstract":"<div><h3>Background</h3><div>Epstein-Barr virus (EBV) exhibits significant molecular diversity, commonly classified into distinct variants based on specific polymorphisms in the latent membrane protein-1 (LMP-1) gene. Traditional analyses have largely relied on Sanger sequencing, which may be limited in detecting mixed variant populations and recombination events.</div></div><div><h3>Objectives</h3><div>This study aimed to evaluate whether high-throughput sequencing (HTS) using Oxford Nanopore Technology (ONT) provides a more comprehensive analysis of LMP-1 variants, particularly in samples previously identified as recombinants by Sanger sequencing.</div></div><div><h3>Study design</h3><div>Twenty-four peripheral blood samples from patients with EBV-associated infectious mononucleosis (IM), previously analysed by Sanger sequencing, were reevaluated using full-length LMP-1 sequencing via ONT.</div></div><div><h3>Results</h3><div>ONT sequencing enabled the reclassification of 11 samples initially identified as recombinants by Sanger sequencing as coinfections, based on the presence of dual polymorphisms at the same nucleotide positions. The remaining 12 samples showed concordant results with Sanger data, confirming their recombinant nature. Additionally, ONT identified an amino acid substitution at position 366 in 5/24 samples, leading to further reclassification of LMP-1 variants. In one case, ONT detected only a single LMP-1 variant (China1), contradicting earlier recombinant classification.</div></div><div><h3>Conclusions</h3><div>ONT-based HTS enables more detailed detection of LMP-1 recombinants and coinfections, offering a broader view of EBV molecular diversity compared to Sanger sequencing. This approach has potential implications for identifying high-risk EBV variants associated with malignancy and demonstrates feasibility for implementation in routine clinical virology. To our knowledge, this is the first study to apply ONT for comprehensive molecular analysis of EBV LMP-1 coinfections.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"41 ","pages":"Article 102369"},"PeriodicalIF":0.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145412790","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}